Urgent-Start Peritoneal Dialysis and Hemodialysis in ESRD Patients: Complications and Outcomes.

PubMed

Jin, Haijiao; Fang, Wei; Zhu, Mingli; Yu, Zanzhe; Fang, Yan; Yan, Hao; Zhang, Minfang; Wang, Qin; Che, Xiajing; Xie, Yuanyuan; Huang, Jiaying; Hu, Chunhua; Zhang, Haifen; Mou, Shan; Ni, Zhaohui

2016-01-01

Several studies have suggested that urgent-start peritoneal dialysis (PD) is a feasible alternative to hemodialysis (HD) in patients with end-stage renal disease (ESRD), but the impact of the dialysis modality on outcome, especially on short-term complications, in urgent-start dialysis has not been directly evaluated. The aim of the current study was to compare the complications and outcomes of PD and HD in urgent-start dialysis ESRD patients. In this retrospective study, ESRD patients who initiated dialysis urgently without a pre-established functional vascular access or PD catheter at a single center from January 2013 to December 2014 were included. Patients were grouped according to their dialysis modality (PD and HD). Each patient was followed for at least 30 days after catheter insertion (until January 2016). Dialysis-related complications and patient survival were compared between the two groups. Our study enrolled 178 patients (56.2% male), of whom 96 and 82 patients were in the PD and HD groups, respectively. Compared with HD patients, PD patients had more cardiovascular disease, less heart failure, higher levels of serum potassium, hemoglobin, serum albumin, serum pre-albumin, and lower levels of brain natriuretic peptide. There were no significant differences in gender, age, use of steroids, early referral to a nephrologist, prevalence of primary renal diseases, prevalence of co-morbidities, and other laboratory characteristics between the groups. The incidence of dialysis-related complications during the first 30 days was significantly higher in HD than PD patients. HD patients had a significantly higher probability of bacteremia compared to PD patients. HD was an independent predictor of short-term (30-day) dialysis-related complications. There was no significant difference between PD and HD patients with respect to patient survival rate. In an experienced center, PD is a safe and feasible dialysis alternative to HD for ESRD patients with an urgent need for dialysis.

Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients.

PubMed

Li, Zhenguang; Yu, Zhancai; Zhang, Jinbiao; Wang, Jing; Sun, Chao; Wang, Pengfei; Zhang, Jiangshan

2015-01-01

The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. Data from 176 PD patients participating in the collaborative PD study between June 2010 and June 2014 were collected; the Chinese edition of the Montreal Cognitive Assessment (MoCA) score was used to evaluate the cognitive function of patients, and falls were recorded. PD patients with cognitive dysfunction were randomly administered either a placebo or Rivastigmine. The cognitive function changes and difference in fall incidence were compared between the 2 groups. The average number of falls per person in PD patients without cognitive impairment dysfunction was significantly lower than that in patients in the PD mild cognitive impairment (PD-MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001, respectively), and the incidence of falls was significantly lower than that in patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively). Compared to the PD-MCI group, the incidence of falls of patients in the PDD group (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were significantly increased (p < 0.01). After taking the placebo or Rivastigmine for 12 months, the MoCA scores of patients in the Rivastigmine treatment group were significantly higher than those of the control group (p = 0.002). The number of falls per person and the incidence of falls of patients in Rivastigmine treatment group were significantly lower than those in the placebo group (p < 0.01). This study suggests that the degree of cognitive impairment is closely associated with the incidence of falls, and the cholinesterase inhibitor Rivastigmine can delay the deterioration of cognitive function and lower the incidence of falls in PD patients. © 2015 S. Karger AG, Basel.

Gut microbiota in patients with Parkinson's disease in southern China.

PubMed

Lin, Aiqun; Zheng, Wenxia; He, Yan; Tang, Wenli; Wei, Xiaobo; He, Rongni; Huang, Wei; Su, Yuying; Huang, Yaowei; Zhou, Hongwei; Xie, Huifang

2018-05-16

Accumulating evidence has revealed alterations in the communication between the gut and brain in patients with Parkinson's disease (PD), and previous studies have confirmed that alterations in the gut microbiome play an important role in the pathogenesis of numerous diseases, including PD. The aim of this study was to determine whether the faecal microbiome of PD patients in southern China differs from that of control subjects and whether the gut microbiome composition alters among different PD motor phenotypes. We compared the gut microbiota composition of 75 patients with PD and 45 age-matched controls using 16S rRNA next-generation-sequencing. We observed significant increases in the abundance of four bacterial families and significant decreases in the abundance of seventeen bacterial families in patients with PD compared to those of the controls. In particular, the abundance of Lachnospiraceae was reduced by 42.9% in patients with PD, whereas Bifidobacteriaceae was enriched in patients with PD. We did not identify a significant difference in the overall microbial composition among different PD motor phenotypes, but we identified the association between specific taxas and different PD motor phenotypes. PD is accompanied by alterations in the abundance of specific gut microbes. The abundance of certain gut microbes was altered depending on clinical motor phenotypes. Based on our findings, the gut microbiome may be a potential PD biomarker. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cost comparison of peritoneal dialysis versus hemodialysis in end-stage renal disease.

PubMed

Berger, Ariel; Edelsberg, John; Inglese, Gary W; Bhattacharyya, Samir K; Oster, Gerry

2009-08-01

To compare healthcare utilization and costs in patients with end-stage renal disease (ESRD) beginning peritoneal dialysis (PD) or hemodialysis (HD). Retrospective cohort study. Using a US health insurance database, we identified all patients with ESRD who began dialysis between January 1, 2004, and December 31, 2006. Patients were designated as PD patients or as HD patients based on first-noted treatment. Patients with less than 6 months of pretreatment data and those with less than 12 months of data following initiation of dialysis ("pretreatment" and "follow-up," respectively) were dropped from the study sample. The PD patients were matched to HD patients using propensity scoring to control for differences in pretreatment characteristics. Healthcare utilization and costs were then compared over 12 months between propensity-matched PD patients and HD patients using paired t tests and Wilcoxon signed rank tests for continuous variables and using Bowker and McNemar tests for categorical variables, as appropriate. A total of 463 patients met all study entrance criteria; 56 (12%) began treatment with PD, and 407 (88%) began treatment with HD. Fifty PD patients could be propensity matched to an equal number of HD patients. The HD patients were more than twice as likely as matched PD patients to be hospitalized over the subsequent 12 months (hazard ratio, 2.17; 95% confidence interval, 1.34-3.51; P <.01). Their median healthcare costs over the 12-month follow-up period were $43,510 higher ($173,507 vs $129,997 for PD patients, P = .03). Among patients with ESRD, PD patients are less likely than HD patients to be hospitalized in the year following initiation of dialysis. They also have significantly lower total healthcare costs.

Color Discrimination in Patients with Gaucher Disease and Parkinson Disease.

PubMed

Simon-Tov, Shlomi; Dinur, Tama; Giladi, Nir; Bar-Shira, Anat; Zelis, Mayaan; Zimran, Ari; Elstein, Deborah

2015-01-01

Poor color discrimination among patients with Parkinson disease (PD) has long been recognized. It has been shown that carrying one or two mutations in the β-glucocerebrosidase gene (GBA) for the autosomal disease Gaucher disease (GD), as based initially on clinical evidence, is a genetic risk factor for early-onset PD. The purpose of this study was to assess color discrimination in patients with one or two GBA mutations relative to healthy controls to ascertain whether this function is affected when persons with GD or even one GBA mutation develop PD. The Farnsworth-Munsell 100 hue test (FMHT) was evaluated among patients with GD+PD compared to patients with GD only, obligate GBA carriers with and without PD, patients with PD only, and healthy controls. FMHT outcome include computer-generated TES (Total Error Score) and values recommended by Vingrys & King-Smith. Six groups of 10 persons were tested. Significant differences were seen for male GD+PD and for age in PD. The highest mean TES was in the PD only group, the lowest in the GD only group. There was a significant difference because of PD in groups with GD and GBA carriers. GD+PD means were between GD only and PD only mean scores. These findings confirm that PD impacts color discrimination, more in males with GD+PD but nonetheless, GD+PD patients (but not GBA carriers) had better scores than PD only patients.

Mitochondrial dysfunction of immortalized human adipose tissue-derived mesenchymal stromal cells from patients with Parkinson's disease.

PubMed

Moon, Hyo Eun; Yoon, Seung Hee; Hur, Yong Suk; Park, Hyung Woo; Ha, Ji Young; Kim, Kyung-Hee; Shim, Jung Hee; Yoo, Seung Hyun; Son, Jin H; Paek, Seung Leal; Kim, In Keyoung; Hwang, Jae Ha; Kim, Dong Gyu; Kim, Han-Joon; Jeon, Beom Seok; Park, Sung Sup; Paek, Sun Ha

2013-12-01

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.

Mitochondrial Dysfunction of Immortalized Human Adipose Tissue-Derived Mesenchymal Stromal Cells from Patients with Parkinson's Disease

PubMed Central

Moon, Hyo Eun; Yoon, Seung Hee; Hur, Yong Suk; Park, Hyung Woo; Ha, Ji Young; Kim, Kyung-Hee; Shim, Jung Hee; Yoo, Seung Hyun; Son, Jin H.; Paek, Seung Leal; Kim, In Keyoung; Hwang, Jae Ha; Kim, Dong Gyu; Kim, Han-Joon; Jeon, Beom Seok; Park, Sung Sup

2013-01-01

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD. PMID:24465144

The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma.

PubMed

Gwynn, Morgan E; DeRemer, David L

2018-01-01

To summarize and evaluate immunotherapy agents targeting programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) recently approved for the treatment of metastatic urothelial carcinomas (UC). A literature review was performed using PubMed (2012 to June 2017), the American Society of Clinical Oncology abstract databases (2012 to June 2017 Annual Meetings/symposia), and the America Association for Cancer Research symposia (2012 to June 2017). A search using clinicaltrials.gov was conducted to identify studies for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab. English language phase I to III studies assessing PD-1 and PD-L1 in UC were incorporated. Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti-PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. Greater objective response rates seem to be observed in PD-L1-positive patients versus PD-L1-negative patients, but methodologies in this assessment differ among clinical trials. The identification of biomarkers that provide greater insight into patients who positively respond to PD-1/PD-L1 therapies are needed. Treatment options for metastatic UC have expanded to include PD-1/PD-L1 therapies. These agents should be strongly considered as second-line therapy over single-agent chemotherapy for patients who fail or progress after platinum-based treatment.

Increased percentages of PD-1 on CD4+ T cells is associated with higher INF-γ production and altered IL-17 production in patients with systemic lupus erythematosus.

PubMed

Dolff, S; Quandt, D; Feldkamp, T; Jun, C; Mitchell, A; Hua, F; Specker, C; Kribben, A; Witzke, O; Wilde, B

2014-01-01

Programmed death (PD)-1 is a cell death receptor that, upon stimulation, leads to apoptosis. Previous studies have shown alteration of PD-1 expression on T cells and PD-1 genes in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess the expression of this receptor on effector T cells in patients with SLE. In this study we enrolled 32 SLE patients and 31 healthy controls. T cells from peripheral blood were analysed by flow cytometry for the expression of PD-1. Interferon (IFN)-γ and interleukin (IL)-17-producing cells were investigated for the expression of this co-stimulatory marker. Percentages of CD4(+) T cells expressing PD-1 were significantly increased in patients with SLE compared to healthy controls. The percentage of PD-1 expression was correlated with the production of INF-γ (r = 0.83, p < 0.0001). We also investigated the production of IL-17 by PD-1(+) CD3(+) T cells. Inactive patients (3.2 ± 1.2% vs. 5.9 ± 3.5%, p = 0.002) and patients without lupus nephritis (LN) (3.2 ± 1.5% vs. 5.9 ± 3.5%, p = 0.005) showed lower levels of IL-17 compared to healthy controls. We have demonstrated increased expression of PD-1 on CD4(+) T cells in SLE patients and an association between PD-1 expression on CD4(+) T cells and IFN-γ expression on CD3(+) T cells. We have also shown that there is an altered subset of PD-1(+) T cells in inactive patients and patients without LN producing lower amounts of IL-17.

Elevated Serum Pesticide Levels and Risk of Parkinson Disease

PubMed Central

Richardson, Jason R.; Shalat, Stuart L.; Buckley, Brian; Winnik, Bozena; O’Suilleabhain, Padraig; Diaz-Arrastia, Ramon; Reisch, Joan; German, Dwight C.

2012-01-01

Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD. PMID:19597089

Lower education level is a major risk factor for peritonitis incidence in chronic peritoneal dialysis patients: a retrospective cohort study with 12-year follow-up.

PubMed

Chern, Yahn-Bor; Ho, Pei-Shan; Kuo, Li-Chueh; Chen, Jin-Bor

2013-01-01

Peritoneal dialysis (PD)-related peritonitis remains an important complication in PD patients, potentially causing technique failure and influencing patient outcome. To date, no comprehensive study in the Taiwanese PD population has used a time-dependent statistical method to analyze the factors associated with PD-related peritonitis. Our single-center retrospective cohort study, conducted in southern Taiwan between February 1999 and July 2010, used time-dependent statistical methods to analyze the factors associated with PD-related peritonitis. The study recruited 404 PD patients for analysis, 150 of whom experienced at least 1 episode of peritonitis during the follow-up period. The incidence rate of peritonitis was highest during the first 6 months after PD start. A comparison of patients in the two groups (peritonitis vs null-peritonitis) by univariate analysis showed that the peritonitis group included fewer men (p = 0.048) and more patients of older age (≥65 years, p = 0.049). In addition, patients who had never received compulsory education showed a statistically higher incidence of PD-related peritonitis in the univariate analysis (p = 0.04). A proportional hazards model identified education level (less than elementary school vs any higher education level) as having an independent association with PD-related peritonitis [hazard ratio (HR): 1.45; 95% confidence interval (CI): 1.01 to 2.06; p = 0.045). Comorbidities measured using the Charlson comorbidity index (score >2 vs ≤2) showed borderline statistical significance (HR: 1.44; 95% CI: 1.00 to 2.13; p = 0.053). A lower education level is a major risk factor for PD-related peritonitis independent of age, sex, hypoalbuminemia, and comorbidities. Our study emphasizes that a comprehensive PD education program is crucial for PD patients with a lower education level.

Depression and dementia in Parkinson's disease.

PubMed

Sinanović, Osman; Hudić, Josip; Zukić, Sanela; Kapidžić, Almasa; Zonić, Lejla; Vidović, Mirjana

2015-03-01

Parkinson's disease (PD) is a neurodegenerative disorder causing not only motor dysfunction but also cognitive, psychiatric, autonomic and sensory disturbances. Depression is the most common psychiatric disturbance identified in patients with PD and has been shown to be more common in PD than in other chronic and disabling disorders, occurring in approximately 40% of PD patients. However, the prevalence and clinical features associated with depression in PD remain controversial. Dementia is increasingly recognized as a symptom associated with idiopathic PD, and is found in up to 40% of all patients suffering from that condition. The aim of this study was to estimate the prevalence of depressive and dementia symptoms in PD patients. The study included 35 consecutive patients with PD, 13 (37.4%) male and 22 (62.6%) female (mean age 62.9 ± 11.0, range 36-85 years), mean duration of disease 4.7 ± 2.9 (range 1-10) years, hospitalized during one year at Clinical Department of Neurology, Tuzla University Clinical Center, Tuzla, Bosnia and Herzegovina. The Mini Mental State Examination (MMSE) was used for assessment of cognitive deterioration and Beck Depression Inventory (BDI) for depression. Computerized tomography was performed in all patients. According to BDI scale, depressive symptoms were present in all 35 PD patients: minimal in 4 (11.4%), low in 7 (20%), moderate in 8 (22.8%), severe in 9 (25.4%) and extreme in 7 (20%) patients. On MMSE scale, 9 (25.4%) patients were free from cognitive deterioration and 26 (74.6%) patients had moderate to severe deterioration, but 21 (60%) patients (7 (33.33%) male and 14 (66.66%) female) had symptoms of dementia (MMSE score ≤ 23). Using MMSE scale, 8 (22.8%) patients were free from dementia and 27 (77.2%) patients had some cognitive deterioration. Very mild symptoms of dementia were found in 6 (25.9%) and overt features of dementia in 21 (74.1%) PD patients. So, out of 35 PD study patients, 21 (60%) (7 (33.3%) male and 14 (66.7%) female) had symptoms of dementia (MMSE score ≤ 23). In conclusion, depressive and dementia symptoms are common in PD patients.

The pedunculopontine nucleus is related to visual hallucinations in Parkinson's disease: preliminary results of a voxel-based morphometry study.

PubMed

Janzen, J; van 't Ent, D; Lemstra, A W; Berendse, H W; Barkhof, F; Foncke, E M J

2012-01-01

Visual hallucinations (VH) are common in Parkinson's disease (PD) and lead to a poor quality of life. For a long time, dopaminergic therapy was considered to be the most important risk factor for the development of VH in PD. Recently, the cholinergic system, including the pedunculopontine nucleus (PPN), has been implicated in the pathophysiology of VH. The aim of the present study was to investigate grey matter density of the PPN region and one of its projection areas, the thalamus. Thirteen non-demented PD patients with VH were compared to 16 non-demented PD patients without VH, 13 demented PD patients (PDD) with VH and 11 patients with dementia with Lewy bodies (DLB). Isotropic 3-D T1-weighted MRI images (3T) were analysed using voxel-based morphometry (VBM) with the PPN region and thalamus as ROIs. PD and PDD patients with VH showed grey matter reductions of the PPN region and the thalamus compared to PD patients without VH. VH in PD(D) patients are associated with atrophy of the PPN region and its thalamic target area, suggesting that a cholinergic deficit may be involved in the development of VH in PD(D).

A Comparison of Treatment-Seeking Behavioral Addiction Patients with and without Parkinson's Disease.

PubMed

Sauvaget, Anne; Jiménez-Murcia, Susana; Fernández-Aranda, Fernando; Granero, Roser; Grall-Bronnec, Marie; Victorri-Vigneau, Caroline; Bulteau, Samuel; Derkinderen, Pascal; Vanelle, Jean M; Hakansson, Anders; Mestre-Bach, Gemma; Steward, Trevor; Menchón, José M

2017-01-01

The administration of dopaminergic medication to treat the symptoms of Parkinson's disease (PD) is associated with addictive behaviors and impulse control disorders. Little is known, however, on how PD patients differ from other patients seeking treatments for behavioral addictions. The aim of this study was to compare the characteristics of behavioral addiction patients with and without PD. N  = 2,460 treatment-seeking men diagnosed with a behavioral addiction were recruited from a university hospital. Sociodemographic, impulsivity [Barratt Impulsiveness Scale (BIS-11)], and personality [Temperament and Character Inventory-Revised (TCI-R)] measures were taken upon admission to outpatient treatment. Patients in the PD group were older and had a higher prevalence of mood disorders than patients without PD. In terms of personality characteristics and impulsivity traits, PD patients appeared to present a more functional profile than PD-free patients with a behavioral addiction. Our results suggest that PD patients with a behavioral addiction could be more difficult to detect than their PD-free counterparts in behavioral addiction clinical setting due to their reduced levels of impulsivity and more standard personality traits. As a whole, this suggests that PD patients with a behavioral addiction may have different needs from PD-free behavioral addiction patients and that they could potentially benefit from targeted interventions.

A Comparison of Treatment-Seeking Behavioral Addiction Patients with and without Parkinson’s Disease

PubMed Central

Sauvaget, Anne; Jiménez-Murcia, Susana; Fernández-Aranda, Fernando; Granero, Roser; Grall-Bronnec, Marie; Victorri-Vigneau, Caroline; Bulteau, Samuel; Derkinderen, Pascal; Vanelle, Jean M.; Hakansson, Anders; Mestre-Bach, Gemma; Steward, Trevor; Menchón, José M.

2017-01-01

The administration of dopaminergic medication to treat the symptoms of Parkinson’s disease (PD) is associated with addictive behaviors and impulse control disorders. Little is known, however, on how PD patients differ from other patients seeking treatments for behavioral addictions. The aim of this study was to compare the characteristics of behavioral addiction patients with and without PD. N = 2,460 treatment-seeking men diagnosed with a behavioral addiction were recruited from a university hospital. Sociodemographic, impulsivity [Barratt Impulsiveness Scale (BIS-11)], and personality [Temperament and Character Inventory-Revised (TCI-R)] measures were taken upon admission to outpatient treatment. Patients in the PD group were older and had a higher prevalence of mood disorders than patients without PD. In terms of personality characteristics and impulsivity traits, PD patients appeared to present a more functional profile than PD-free patients with a behavioral addiction. Our results suggest that PD patients with a behavioral addiction could be more difficult to detect than their PD-free counterparts in behavioral addiction clinical setting due to their reduced levels of impulsivity and more standard personality traits. As a whole, this suggests that PD patients with a behavioral addiction may have different needs from PD-free behavioral addiction patients and that they could potentially benefit from targeted interventions. PMID:29163234

Evaluation of non-motor symptoms and their impact on quality of life in patients with Parkinson’s disease, Isfahan, Iran

PubMed Central

Salari, Mehri; Chitsaz, Ahmad; Etemadifar, Masoud; Najafi, Mohammad Reza; Mirmosayyeb, Omid; Bemanalizadeh, Maryam; Panahi, Fatemeh; Mirzajani, Hosna

2017-01-01

Background: Parkinson’s disease (PD) is diagnosed on the basis of motor symptoms, but non-motor symptoms (NMS) have high prevalence in PD and often antecede motor symptoms for years and cause severe disability. This study was conducted to determine the prevalence of NMS in patients with PD. Methods: This cross-sectional study was performed in Isfahan, Iran, on patients with PD. The prevalence of NMS was evaluated by the NMS questionnaire, the NMS scale, and Parkinson's disease questionnaire-39 (PDQ-39). The Mini-Mental Status Examination (MMSE) was used for assessing cognition. Results: A total of 81 patients, including 60 men and 21 women, were recruited for this study. The prevalence of NMS was 100%, and the most commonly reported symptom was fatigue (87.7%); there was a strong correlation between NMS and the quality of life (QOL) of patients with PD (P < 0.001). Conclusion: This study showed that NMS are highly prevalent in the PD population and adversely affect QOL in these patients. Early diagnosis and treatment can improve QOL and can help in disability management of patients with PD. PMID:29114366

Factors influencing the development of early- or late-onset Parkinson's disease in a cohort of South African patients.

PubMed

van der Merwe, Celia; Haylett, William; Harvey, Justin; Lombard, Debbie; Bardien, Soraya; Carr, Jonathan

2012-10-01

Neurodegenerative disorders such as Parkinson's disease (PD) contribute significantly to global disease burden. PD can be categorised into early-onset PD (EOPD) with an age at onset (AAO) of ≤50 years and late-onset PD (LOPD) with an AAO of 50 years. To identify factors influencing EOPD and LOPD development in a group of patients in South Africa (SA). A total of 397 unrelated PD patients were recruited from the Movement Disorders Clinic at Tygerberg Hospital and via the Parkinson's Association of SA. Patient demographic and environmental data were recorded and associations with PD onset (EOPD v. LOPD) were analysed with a Pearson's Chi-squared test. The English- and Afrikaans-speaking (Afrikaner) white patients were analysed separately. Logistic regression analysis showed that ethnicity (p<0.001) and family history (p=0.004) were independently associated with AAO of PD. Average AAO was younger in black, coloured and Afrikaner patients than English-speaking white patients. A positive family history of PD, seen in 31.1% of LOPD patients, was associated with a younger AAO in the study population. These associations may be attributed to specific genetic and/or environmental risk factors that increase PD susceptibility and influence the clinical course of the disorder. More studies on PD in the unique SA populations are required to provide novel insights into mechanisms underlying this debilitating condition.

Olfaction in Parkin carriers in Chinese patients with Parkinson disease.

PubMed

Wang, Ying; Wu, Jian-Jun; Liu, Feng-Tao; Chen, Kui; Chen, Chen; Luo, Su-Shan; Wang, Yi-Xuan; Li, Da-Ke; Guan, Rong-Yuan; Yang, Yu-Jie; An, Yu; Wang, Jian; Sun, Yi-Min

2017-05-01

Olfactory identification was reported to be better among PD (Parkinson disease) patients with Parkin mutations, but previous studies didn't eliminate the interference of other PD related genes on olfaction, and whether olfaction of Parkin mutations patients was better in Chinese population was still unknown. To assess olfaction function among PD patients with Parkin mutations in Chinese population. A total of 226 PD patients with a positive family history or an early-onset age (<50 years) were enrolled for genetic testing of PD related genes by target sequencing and multiple ligation-dependent probe amplification. The clinical data including olfactory function test were investigated. Linear regression was performed to adjust for the covariates between all groups. There were 68 patients found having a negative result in PD genetic testing and 43 patients carrying homozygous or compound heterozygous Parkin mutations. Among them, 49 PD panel negative patients and 33 PD- Parkin patients had results of olfactory assessment. PD -Parkin patients performed significantly better on the Sniffin' Sticks tests than panel negative patients (8.0 ± 1.7 vs. 5.7 ± 1.9, p  <   .001), but still worse compared to healthy controls (9.4 ± 1.5, p  =   .003). These differences persisted after adjusting for confounders. Among Chinese population, PD -Parkin patients had relatively preserved olfaction compared to PD panel negative patients after eliminating the interference of other PD related genes, but were still worse than healthy controls.

Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP): Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis.

PubMed

Birtas Atesoglu, Elif; Tarkun, Pinar; Demirsoy, Esra Terzi; Geduk, Ayfer; Mehtap, Ozgur; Batman, Adnan; Kaya, Fatih; Cekmen, Mustafa Baki; Gulbas, Zafer; Hacıhanefioglu, Abdullah

2016-04-01

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP. © The Author(s) 2014.

Prevalence and hematological indicators of G6PD deficiency in malaria-infected patients.

PubMed

Kotepui, Manas; Uthaisar, Kwuntida; PhunPhuech, Bhukdee; Phiwklam, Nuoil

2016-04-25

This study aimed to evaluate the prevalence and alteration of hematological parameters in malaria patients with a glucose-6-phosphate dehydrogenase (G6PD) deficiency, in the western region of Thailand, an endemic region for malaria. Data about patients with malaria hospitalized between 2013 and 2015 were collected. Clinical and sociodemographic characteristics such as age and gender, diagnosis on admission, and parasitological results were mined from medical records of the laboratory unit of the Phop Phra Hospital in Tak Province, Thailand. Venous blood samples were collected at the time of admission to hospital to determine G6PD deficiency by fluorescence spot test and detect malaria parasites by thick and thin film examination. Other data such as complete blood count and parasite density were also collected and analyzed. Among the 245 malaria cases, 28 (11.4 %) were diagnosed as Plasmodium falciparum infections and 217 cases (88.6 %) were diagnosed as P. vivax infections. Seventeen (6.9 %) patients had a G6PD deficiency and 228 (93.1 %) patients did not have a G6PD deficiency. Prevalence of male patients with G6PD deficiency was higher than that of female patients (P < 0.05, OR = 5.167). Among the patients with a G6PD deficiency, two (11.8 %) were infected with P. falciparum, while the remaining were infected with P. vivax. Malaria patients with a G6PD deficiency have higher monocyte counts (0.6 × 10(3)/μL) than those without a G6PD deficiency (0.33 × 10(3)/μL) (P < 0.05, OR = 5.167). Univariate and multivariate analyses also confirmed that malaria patients with a G6PD deficiency have high monocyte counts. The association between G6PD status and monocyte counts was independent of age, gender, nationality, Plasmodium species, and parasite density (P < 0.005). This study showed a prevalence of G6PD deficiency in a malaria-endemic area. This study also supported the assertion that patients with G6PD-deficient red blood cells had no protection against the P. falciparum infection. In addition, malaria patients with a G6PD deficiency had higher monocyte counts than those without a G6PD deficiency. These findings will help to recognize and diagnose malaria patients with a G6PD deficiency, as well as to identify the risks and protective factors against malaria in endemic areas.

Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis

PubMed Central

2014-01-01

Introduction A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognized phenomenon of T cell exhaustion is mediated in part by PD-1 effects on T cells. This study tested the ability of anti-PD-1 and anti-PD-L1 antibodies to prevent apoptosis and improve lymphocyte function in septic patients. Methods Blood was obtained from 43 septic and 15 non-septic critically-ill patients. Effects of anti-PD-1, anti-PD-L1, or isotype-control antibody on lymphocyte apoptosis and interferon gamma (IFN-γ) and interleukin-2 (IL-2) production were quantitated by flow cytometry. Results Lymphocytes from septic patients produced decreased IFN-γ and IL-2 and had increased CD8 T cell expression of PD-1 and decreased PD-L1 expression compared to non-septic patients (P<0.05). Monocytes from septic patients had increased PD-L1 and decreased HLA-DR expression compared to non-septic patients (P<0.01). CD8 T cell expression of PD-1 increased over time in ICU as PD-L1, IFN-γ, and IL2 decreased. In addition, donors with the highest CD8 PD-1 expression together with the lowest CD8 PD-L1 expression also had lower levels of HLA-DR expression in monocytes, and an increased rate of secondary infections, suggestive of a more immune exhausted phenotype. Treatment of cells from septic patients with anti-PD-1 or anti-PD-L1 antibody decreased apoptosis and increased IFN-γ and IL-2 production in septic patients; (P<0.01). The percentage of CD4 T cells that were PD-1 positive correlated with the degree of cellular apoptosis (P<0.01). Conclusions In vitro blockade of the PD-1:PD-L1 pathway decreases apoptosis and improves immune cell function in septic patients. The current results together with multiple positive studies of anti-PD-1 and anti-PD-L1 in animal models of bacterial and fungal infections and the relative safety profile of anti-PD-1/anti-PD-L1 in human oncology trials to date strongly support the initiation of clinical trials testing these antibodies in sepsis, a disorder with a high mortality. PMID:24387680

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study.

PubMed

Kalbe, Elke; Rehberg, Sarah Petra; Heber, Ines; Kronenbuerger, Martin; Schulz, Jörg B; Storch, Alexander; Linse, Katharina; Schneider, Christine; Gräber, Susanne; Liepelt-Scarfone, Inga; Berg, Daniela; Dams, Judith; Balzer-Geldsetzer, Monika; Hilker, Rüdiger; Oberschmidt, Carola; Witt, Karsten; Schmidt, Nele; Mollenhauer, Brit; Trenkwalder, Claudia; Spottke, Annika; Roeske, Sandra; Wittchen, Hans-Ulrich; Riedel, Oliver; Dodel, Richard

2016-10-01

Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Association of Thiazolidinedione with a Lower Risk of Parkinson's Disease in a Population with Newly-Diagnosed Diabetes Mellitus.

PubMed

Lin, Hsiu-Li; Lin, Hsiu-Chen; Tseng, Yuan-Fu; Chao, Jane Chen-Jui; Hsu, Chien-Yeh

2018-06-11

We investigated the association of thiazolidinedione and its dose effect with the risk of Parkinson's disease (PD) in patients with diabetes mellitus (DM). This study enrolled 38,521 patients with newly-diagnosed DM between 2001 and 2013 and compared them to matched subjects without DM. The hazard ratios (HRs) for PD were compared between the thiazolidinedione-treated and non-thiazolidinedione-treated groups of the study cohort, and between subgroups who received different cumulative dosages of thiazolidinedione. We observed 544 (1.4%) patients with PD during the follow up of median duration of 6.2 years in patients with newly-diagnosed DM who had a higher risk for PD than patients without DM (HR = 1.150). In the study cohort, the risk of PD was significantly lower in the thiazolidinedione-treated group (HR = 0.399) compared to the non-thiazolidinedione-treated group. Thiazolidinedione reduced the risk of PD in a dose-dependent manner, with HRs ranging from 0.613 to 0.081 with defined daily doses of 0-90 to > 720, respectively. Thiazolidinedione use was associated with a significantly reduced risk of PD in patients with newly-diagnosed DM. Further studies to elucidate the common mechanism of PD and DM may provide novel therapies for these two diseases.

Parkinson's patients' executive profile and goals they set for improvement: Why is cognitive rehabilitation not common practice?

PubMed

Vlagsma, T T; Koerts, J; Fasotti, L; Tucha, O; van Laar, T; Dijkstra, H; Spikman, J M

2016-01-01

Impairments in executive functions (EF) are the core cognitive impairment in patients with Parkinson's disease (PD). Surprisingly, cognitive rehabilitation is not routinely offered to patients with PD. However, in patients with acquired brain injury (ABI), cognitive rehabilitation, in particular strategic executive training, is common practice and has been shown to be effective. In this study, we determined whether PD patients have different needs and aims with regard to strategic executive training than ABI patients, and whether possible differences might be a reason for not offering this kind of cognitive rehabilitation programme to patients with PD. Patients' needs and aims were operationalised by individually set goals, which were classified into domains of EF and daily life. In addition, patients with PD and ABI were compared on their cognitive, in particular EF, profile. Overall, PD patients' goals and cognitive profile were similar to those of patients with ABI. Therefore, based on the findings of this study, there is no reason to assume that strategic executive training cannot be part of standard therapy in PD. However, when strategic executive training is applied in clinical practice, disease-specific characteristics need to be taken into account.

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

PubMed

Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi; Korbo, Lise; Friberg, Lars; Jennum, Poul

2016-06-15

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ((123)I-FP-CIT SPECT), neurological examination, and polysomnography. iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. (123)I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to (123)I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. © 2016 American Academy of Sleep Medicine.

Effect of Dopamine Therapy on Nonverbal Affect Burst Recognition in Parkinson's Disease

PubMed Central

Péron, Julie; Grandjean, Didier; Drapier, Sophie; Vérin, Marc

2014-01-01

Background Parkinson's disease (PD) provides a model for investigating the involvement of the basal ganglia and mesolimbic dopaminergic system in the recognition of emotions from voices (i.e., emotional prosody). Although previous studies of emotional prosody recognition in PD have reported evidence of impairment, none of them compared PD patients at different stages of the disease, or ON and OFF dopamine replacement therapy, making it difficult to determine whether their impairment was due to general cognitive deterioration or to a more specific dopaminergic deficit. Methods We explored the involvement of the dopaminergic pathways in the recognition of nonverbal affect bursts (onomatopoeias) in 15 newly diagnosed PD patients in the early stages of the disease, 15 PD patients in the advanced stages of the disease and 15 healthy controls. The early PD group was studied in two conditions: ON and OFF dopaminergic therapy. Results Results showed that the early PD patients performed more poorly in the ON condition than in the OFF one, for overall emotion recognition, as well as for the recognition of anger, disgust and fear. Additionally, for anger, the early PD ON patients performed more poorly than controls. For overall emotion recognition, both advanced PD patients and early PD ON patients performed more poorly than controls. Analysis of continuous ratings on target and nontarget visual analog scales confirmed these patterns of results, showing a systematic emotional bias in both the advanced PD and early PD ON (but not OFF) patients compared with controls. Conclusions These results i) confirm the involvement of the dopaminergic pathways and basal ganglia in emotional prosody recognition, and ii) suggest a possibly deleterious effect of dopatherapy on affective abilities in the early stages of PD. PMID:24651759

Depression and Parkinson disease: prevalence, temporal relationship, and determinants.

PubMed

Yapici Eser, Hale; Bora, Hatice Ayşe; Kuruoğlu, Aslı

2017-04-18

Comorbidity of depression in Parkinson disease (PD) is a major factor that changes patients' quality of life. However, the neurobiological and sociodemographic risk factors for this comorbidity are not well studied. In this study, we aimed to define the prevalence, temporal relationship, and psychosocial and clinical determinants of depression comorbid with PD. Fifty-five PD patients were evaluated with SCID, a data form that assessed sociodemographic and PD-related variables, UPDRS III, HAM-D, HAM-A, MMSE, and the Apathy Evaluation Scale. Depression (lifetime: 45.5%, last month: 25.5%, before PD: 20%) was the most frequent psychiatric diagnosis. The major determinants of depression in the last month and depression before PD were early onset of PD and young age. Patients on pramipexole treatment were less likely to be diagnosed with depression in the last month. Other sociodemographic and PD-related variables were not significantly different for lifetime, last month, and pre-PD depression diagnosis compared to their counterparts. Depression is prevalent both before and after patient gets a PD diagnosis. Depression is not only the result of PD-related life changes but it is also a preceding factor that may decrease the age of PD onset.

Prevalence of Cognitive Impairment Among Peritoneal Dialysis Patients, Impact on Peritonitis and Role of Assisted Dialysis.

PubMed

Shea, Yat Fung; Lam, Man Fai; Lee, Mi Suen Connie; Mok, Ming Yee Maggie; Lui, Sing-Leung; Yip, Terence P S; Lo, Wai Kei; Chu, Leung Wing; Chan, Tak-Mao

2016-01-01

♦ Chronic renal failure and aging are suggested as risk factors for cognitive impairment (CI). We studied the prevalence of CI among peritoneal dialysis (PD) patients using Montreal Cognitive Assessment (MoCA), its impact on PD-related peritonitis in the first year, and the potential role of assisted PD. ♦ One hundred fourteen patients were newly started on PD between February 2011 and July 2013. Montreal Cognitive Assessment was performed in the absence of acute illness. Data on patient characteristics including demographics, comorbidities, blood parameters, dialysis adequacy, presence of helpers, medications, and the number PD-related infections were collected. ♦ The age of studied patients was 59±15.0 years, and 47% were female. The prevalence of CI was 28.9%. Patients older than 65 years old (odds ratio [OR] 4.88, confidence interval [CI] 1.79 - 13.28 p = 0.002) and with an education of primary level or below (OR 4.08, CI 1.30 - 12.81, p = 0.016) were independent risk factors for CI in multivariate analysis. Patients with PD-related peritonitis were significantly older (p < 0.001) and more likely to have CI as defined by MoCA (p = 0.035). After adjustment for age, however, CI was not a significant independent risk factor for PD-related peritonitis among self-care PD patients (OR 2.20, CI 0.65 - 7.44, p = 0.20). When we compared patients with MoCA-defined CI receiving self-care and assisted PD, there were no statistically significant differences between the 2 groups in terms of age, MoCA scores, or comorbidities. There were also no statistically significant differences in 1-year outcome of PD-related peritonitis rates or exit-site infections. ♦ Cognitive impairment is common among local PD patients. Even with CI, peritonitis rate in self-care PD with adequate training is similar to CI patients on assisted PD. Copyright © 2016 International Society for Peritoneal Dialysis.

Effectiveness of anti-PD-1/PD-L1 antibodies in urothelial carcinoma patients with different PD-L1 expression levels: a meta-analysis.

PubMed

Liu, Junqi; Zhang, Chuanfeng; Hu, Jiegang; Tian, Qing; Wang, Xin; Gu, Hao; Zhang, Song; Zhao, Di; Fan, Ruitai

2018-02-23

Urothelial carcinoma ranks the ninth among malignant cancers. We conducted this study to identify which patients could benefit more from the treatment of programmed death-1 (PD-1)/programmed death-ligand1 (PD-L1) inhibitors. We performed literature searches, combined data from qualified literature and performed comparative analyses on the effectiveness of anti-PD-1/PD-L1 antibodies in patients with different PD-L1 expression levels. We divided patients into three groups according to the percentages of PD-L1-positive cells, namely the low- PD-L1 (PD-L1 < 1%), the medium-PD-L1 (PD-L1 ≥ 1 and < 5%) and the high-PD-L1 (PD-L1 ≥ 5%) groups. We found that the high-PD-L1 group responded significantly better than other groups (P = 0.0003, ORs = 0.45, 95%CI: 0.29-071; P = 0.0009, ORs = 0.43, 95%CI: 0.25-0.73, for low-PD-L1 and medium-PD-L1 groups, respectively), while the latter two groups responded similarly (P = 0.90, ORs = 1.06, 95%CI: 0.62-1.83) to both PD-1 and PD-L1 inhibitors. Furthermore, we found that the medium-PD-L1 and high-PD-L1 groups responded similarly to PD-1/ PD-L1 inhibitors (P = 0.65, ORs = 1.11, 95%CI: 0.69-1.77), while the low-PD-L1 group responded better to PD-1 inhibitors than PD-L1 inhibitors (P = 0.046, ORs = 1.92, 95%CI: 0.98-3.89). Our results suggest that PD-L1 positive patients should be defined as those with ≥ 5% or greaterPD-L1-positive cells. PD-1 antibodies performed better only in the low-group patients, likely because they could block the interactions of PD-1 with both PD-L1 and PD-L2.

Comparing the Incidence of Falls/Fractures in Parkinson's Disease Patients in the US Population.

PubMed

Kalilani, Linda; Asgharnejad, Mahnaz; Palokangas, Tuire; Durgin, Tracy

2016-01-01

Patients with Parkinson's disease (PD) may experience falls and/or fractures as a result of disease symptoms. There are limited data available from long-term studies estimating the incidence of falls/fractures in patients with PD. The objective was to compare the incidence rate of falls/fractures in PD patients with non-PD patients in a US population. This was a retrospective study using a US-based claims database (Truven Health MarketScan®) that compared the incidence rate of falls/fractures in PD subjects with non-PD subjects. The study period included the 12 months prior to index date (defined as earliest PD diagnosis [International Classification of Diseases, Ninth Revision, Clinical Modification code 332.0]) and a postindex period to the end of data availability. Fractures were defined by inpatient/outpatient claims as a principal or secondary diagnosis and accompanying procedure codes during the postindex period. Incidence rates and 95% CIs for falls/fractures were calculated as the number of events per 10,000 person-years of follow-up using negative binomial or Poisson regression models. Twenty-eight thousand two hundred and eighty PD subjects were matched to non-PD subjects for the analysis (mean [SD] age, 71.4 [11.8] years; 53% male). A higher incidence rate (adjusted for comorbidities and medications) of all fall/fracture cases and by fall and fracture types was observed for PD subjects versus non-PD subjects; the overall adjusted incidence rate ratio comparing PD to non-PD subjects was 2.05; 95% CI, 1.88-2.24. The incidence rate of falls/fractures was significantly higher in subjects with PD compared with non-PD subjects in a US population.

Childhood Traumatic Experiences, Dissociative Symptoms, and Dissociative Disorder Comorbidity Among Patients With Panic Disorder: A Preliminary Study.

PubMed

Ural, Cenk; Belli, Hasan; Akbudak, Mahir; Tabo, Abdulkadir

2015-01-01

This study assessed childhood trauma history, dissociative symptoms, and dissociative disorder comorbidity in patients with panic disorder (PD). A total of 92 psychotropic drug-naive patients with PD, recruited from outpatient clinics in the psychiatry department of a Turkish hospital, were involved in the study. Participants were assessed using the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D), Dissociation Questionnaire, Panic and Agoraphobia Scale, Panic Disorder Severity Scale, and Childhood Trauma Questionnaire. Of the patients with PD, 18 (19%) had a comorbid dissociative disorder diagnosis on screening with the SCID-D. The most prevalent disorders were dissociative disorder not otherwise specified, dissociative amnesia, and depersonalization disorders. Patients with a high degree of dissociation symptoms and dissociative disorder comorbidity had more severe PD than those without (p < .05). All of the childhood trauma subscales used were correlated with the severity of symptoms of dissociation and PD. Among all of the subscales, the strongest relationship was with childhood emotional abuse. Logistic regression analysis showed that emotional abuse and severity of PD were independently associated with dissociative disorder. In our study, a significant proportion of the patients with PD had concurrent diagnoses of dissociative disorder. We conclude that the predominance of PD symptoms at admission should not lead the clinician to overlook the underlying dissociative process and associated traumatic experiences among these patients.

Effect of dialysis modality on frailty phenotype, disability, and health-related quality of life in maintenance dialysis patients

PubMed Central

Kang, Seok Hui; Do, Jun Young; Lee, So-Young; Kim, Jun Chul

2017-01-01

Background Health-related quality of life (HRQoL) surveys are needed to evaluate regional and ethnic specificies. The aim of the present study was to evaluate the differences in HRQoL, frailty, and disability according to dialysis modality in the Korean population. Patients and methods We enrolled relatively stable maintenance dialysis patients. A total of 1,616 patients were recruited into our study. The demographic and laboratory data collected at enrollment included age, sex, comorbidities, frailty, disability, and HRQoL scales. Results A total of 1,250 and 366 participants underwent hemodialysis (HD) and peritoneal dialysis (PD), respectively. The numbers of participants with pre-frailty and frailty were 578 (46.2%) and 422 (33.8%) in HD patients, and 165 (45.1%) and 137 (37.4%) in PD patients, respectively (P = 0.349). Participants with a disability included 195 (15.6%) HD patients and 109 (29.8%) PD patients (P < 0.001). On multivariate analysis, the mean physical component scale (PCS) and mental component scale (MCS), symptom/problems, and sleep scores were higher in HD patients than in PD patients. Cox regression analyses showed that an increased PCS in both HD and PD patients was positively associated with patient survival and first hospitalization–free survival. An increased MCS in both HD and PD patients was positively associated with first hospitalization–free survival only. Conclusion There was no significant difference in frailty between patients treated with the two dialysis modalities; however, disability was more common in PD patients than in HD patients. The MCS and PCS were more favorable in HD patients than in PD patients. Symptom/problems, sleep, quality of social interaction, and social support were more favorable in HD patients than in PD patients; however, patient satisfaction and dialysis staff encouragement were more favorable in PD patients than in HD patients. PMID:28467472

Mood and neural correlates of excessive daytime sleepiness in Parkinson's disease.

PubMed

Wen, M-C; Chan, L L; Tan, L C S; Tan, E K

2017-08-01

For patients with Parkinson's disease (PD), excessive daytime sleepiness (PD-EDS) is a debilitating non-motor symptom and may be affected by mood symptoms, especially depression and anxiety. Few neuroimaging works have attempted to identify the neural features of PD-EDS, but various findings were reported. The purpose of this study was to systematically review the literature on mood and neuroimaging correlates of PD-EDS. A MEDLINE, PubMed, EMBASE, and PsycInfo search for peer-reviewed original research articles on depression, anxiety, and neuroimaging in PD-EDS identified 26 studies on depression, nine on anxiety, and eight on neuroimaging. Half of the studies reported greater depression in PD-EDS-positive patients compared with PD-EDS-negative patients. There was a significantly positive correlation between depression and PD-EDS. Limited studies on anxiety in PD-EDS suggested a weak correlation between anxiety and EDS. For depression and anxiety, the effect sizes were medium when EDS was subjectively measured, but became small when EDS was objective measured. Current neuroimaging studies generally suggested diminished neural structural and functional features (eg, brain volume, white matter integrity as indicated by fractional anisotropy, and cerebral metabolism) in patients with PD-EDS. Future studies should apply objective and subjective measures of mood symptoms and EDS and improve the neuroimaging methodology via using multimodal techniques and whole-brain analysis to provide new clues on the mood and neural correlates of PD-EDS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Swallowing impairment and pulmonary dysfunction in Parkinson's disease: the silent threats.

PubMed

Monteiro, Larissa; Souza-Machado, Adelmir; Pinho, Patrícia; Sampaio, Marília; Nóbrega, Ana Caline; Melo, Ailton

2014-04-15

Swallowing disorders and respiratory impairment are frequent in Parkinson's disease (PD) patients, and aspiration pneumonia remains the leading cause of death among these subjects. The objective of this study was to investigate whether there is an association between pulmonary impairment and swallowing dysfunction in PD patients. A cross-sectional study with a comparison group was conducted with PD patients. Subjects were submitted to demographic questionnaires and underwent spirometric and videofluorographic assessments. Significance level was considered at 95% (p<0.05). Among 35 PD patients, 40% presented with swallowing complaints. However, 22% of the clinically asymptomatic patients presented airway food penetration when submitted to videofluoroscopy. In 20% of PD patients material entered the airways and there was contact with the vocal folds in 7%. However, there was an efficient cleaning with residue deglutition in almost all patients. No penetration/aspiration was detected among the controls. Respiratory parameters were below the normal predicted values in PD patients when compared to the healthy controls. These data suggest an association between pulmonary dysfunction and swallowing impairment in PD patients; even in patients without swallowing complaints, impaired pulmonary function can be detected. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of dialysis modality on frailty phenotype, disability, and health-related quality of life in maintenance dialysis patients.

PubMed

Kang, Seok Hui; Do, Jun Young; Lee, So-Young; Kim, Jun Chul

2017-01-01

Health-related quality of life (HRQoL) surveys are needed to evaluate regional and ethnic specificies. The aim of the present study was to evaluate the differences in HRQoL, frailty, and disability according to dialysis modality in the Korean population. We enrolled relatively stable maintenance dialysis patients. A total of 1,616 patients were recruited into our study. The demographic and laboratory data collected at enrollment included age, sex, comorbidities, frailty, disability, and HRQoL scales. A total of 1,250 and 366 participants underwent hemodialysis (HD) and peritoneal dialysis (PD), respectively. The numbers of participants with pre-frailty and frailty were 578 (46.2%) and 422 (33.8%) in HD patients, and 165 (45.1%) and 137 (37.4%) in PD patients, respectively (P = 0.349). Participants with a disability included 195 (15.6%) HD patients and 109 (29.8%) PD patients (P < 0.001). On multivariate analysis, the mean physical component scale (PCS) and mental component scale (MCS), symptom/problems, and sleep scores were higher in HD patients than in PD patients. Cox regression analyses showed that an increased PCS in both HD and PD patients was positively associated with patient survival and first hospitalization-free survival. An increased MCS in both HD and PD patients was positively associated with first hospitalization-free survival only. There was no significant difference in frailty between patients treated with the two dialysis modalities; however, disability was more common in PD patients than in HD patients. The MCS and PCS were more favorable in HD patients than in PD patients. Symptom/problems, sleep, quality of social interaction, and social support were more favorable in HD patients than in PD patients; however, patient satisfaction and dialysis staff encouragement were more favorable in PD patients than in HD patients.

Influence of Deep Breathing on Heart Rate Variability in Parkinson's Disease: Co-relation with Severity of Disease and Non-Motor Symptom Scale Score.

PubMed

Bidikar, Mukta Pritam; Jagtap, Gayatri J; Chakor, Rahul T

2014-07-01

Dysautonomia and non-motor symptoms (NMS) in Parkinson's disease (PD) are frequent, disabling and reduce quality of life of patient. There is a paucity of studies on autonomic dysfunction in PD in Indian population. The study aimed to evaluate autonomic dysfunction in PD patients and co-relate the findings with severity of PD and Non-Motor Symptoms Scale (NMSS) score. We evaluated autonomic function in 30 diagnosed patients of PD (age 55-70 years) and 30 healthy age-matched controls by 3 min deep breathing test (DBT). NMSS was used to identify non-motor symptoms and Hoehn and Yahr (HY) Scale to grade severity of PD. The DBT findings were co-related with severity of PD (HY staging) and NMSS score. DBT was found to be abnormal in 40% while it was on borderline in 33.3% of PD patients. There was a statistically significant difference (p<0.01) between patients and control group for the DBT. NMS were reported across all the stages of PD but with variable frequency and severity for individual symptom. A negative co-relation was found between results of deep breathing test and clinical severity of disease and NMSS score. Abnormalities of autonomic function and NMS were integral and present across all the stages of PD patients. Early recognition and treatment of these may decrease morbidity and improve quality of life of PD patients.

Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma.

PubMed

Liu, Chao-Qun; Xu, Jing; Zhou, Zhong-Guo; Jin, Li-Lian; Yu, Xing-Juan; Xiao, Gang; Lin, Jie; Zhuang, Shi-Mei; Zhang, Yao-Jun; Zheng, Limin

2018-06-20

Recent clinical studies have suggested that programmed death ligand 1 (PD-L1) expression in a tumour could be a potential biomarker for PD-L1/PD-1 blockade therapies. To better characterise PD-L1 expression in hepatocellular carcinoma (HCC), we analysed its expression patterns in 453 HCC patients by double staining for CD68 and PD-L1 using the Tyramide Signal Amplification Systems combined with immunohistochemistry. We also investigated its correlation with clinical features, prognosis and immune status. The results showed that PD-L1 expression on tumour cells (TCs) was negatively associated with patients' overall survival (OS; P = 0.001) and relapse-free survival (RFS; P = 0.006); however, PD-L1 expression on macrophages (Mφs) was positively correlated with OS (P = 0.017). Multivariate analysis revealed that PD-L1 expression on TCs and Mφs were both independent prognostic factors for OS (hazard ratio (HR) = 1.168, P = 0.004 for TC-PD-L1; HR = 0.708, P = 0.003 for Mφ-PD-L1). Further studies showed that Mφ-PD-L1 + tumours exhibited an activated immune microenvironment, with high levels of CD8 + T-cell infiltration and immune-related gene expression. Our study provided a novel methodology to evaluate PD-L1 expression in the tumour microenvironment, which might help to select patients who would benefit from anti-PD-1/PD-L1 immunotherapies.

Obsessive compulsive personality disorder and Parkinson's disease.

PubMed

Nicoletti, Alessandra; Luca, Antonina; Raciti, Loredana; Contrafatto, Donatella; Bruno, Elisa; Dibilio, Valeria; Sciacca, Giorgia; Mostile, Giovanni; Petralia, Antonio; Zappia, Mario

2013-01-01

To evaluate the frequency of personality disorders in Parkinson's disease (PD) patients and in a group of healthy controls. Patients affected by PD diagnosed according to the United Kingdom Parkinson's disease Society Brain Bank diagnostic criteria and a group of healthy controls were enrolled in the study. PD patients with cognitive impairment were excluded from the study. Structured Clinical Interview for Personality Disorders-II (SCID-II) has been performed to evaluate the presence of personality disorders. Presence of personality disorders, diagnosed according to the DSM-IV, was confirmed by a psychiatric interview. Clinical and pharmacological data were also recorded using a standardized questionnaire. 100 PD patients (57 men; mean age 59.0 ± 10.2 years) and 100 healthy subjects (52 men; mean age 58.1 ± 11.4 years) were enrolled in the study. The most common personality disorder was the obsessive-compulsive personality disorder diagnosed in 40 PD patients and in 10 controls subjects (p-value<0.0001) followed by the depressive personality disorder recorded in 14 PD patients and 4 control subjects (p-value 0.02). Obsessive-compulsive personality disorder was also found in 8 out of 16 de novo PD patients with a short disease duration. PD patients presented a high frequency of obsessive-compulsive personality disorder that does not seem to be related with both disease duration and dopaminergic therapy.

Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients.

PubMed

Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda; Fábián, Katalin; Pipek, Orsolya; Vágvölgyi, Attila; Agócs, László; Fillinger, János; Kajdácsi, Zita; Tímár, József; Döme, Balázs; Szállási, Zoltán; Moldvay, Judit

2018-04-19

While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. We determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy. PD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin-gemcitabine combination (p = 0.020), while in the carboplatin-paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy. This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.

Risk factors of periodontal disease in maintenance hemodialysis patients

PubMed Central

Hou, Yue; Wang, Xin; Zhang, Cong-Xiao; Wei, Yu-Dan; Jiang, Li-Li; Zhu, Xiao-Yu; Du, Yu-Jun

2017-01-01

Abstract To explore the characteristics and relevant risk factors of periodontal disease (PD) among hemodialysis patients. Uremic patients on maintenance hemodialysis from November 2015 to March 2016 were retrospectively reviewed. Patients were divided into a PD group and a non-PD group. Demographic and laboratory data were collected and analyzed. In all, 136 uremic patients (79 males and 57 females, aged 50.8 ± 15.3 years) on maintenance hemodialysis were included in this study. The incidence of PD increased with age. Hemodialysis patients most likely developed PD if they were male, smokers, or diabetic (P = .009, <.001, and <.001, respectively). Patients brushing their teeth twice daily had significantly less chance of developing PD as compared with those only brushing once daily (P < .001). Hemodialysis patients in the PD group had significantly higher levels of total cholesterol, high-sensitivity C-reactive protein, fasting blood glucose, and peripheral white blood cell counts, compared with the non-PD group (all P < .001). Logistic regression analysis revealed that diabetes, total cholesterol, high-sensitivity C-reactive protein, and peripheral white blood cell count were independent risk factors for developing PD, whereas teeth brushing twice daily and serum calcium were favorable factors for maintenance hemodialysis patients against PD. Identification of risk factors provides a theoretical basis for prevention and improvement of PD among maintenance hemodialysis patients. PMID:28858105

A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non-Small-Cell Lung Cancer Patients.

PubMed

Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Shimokawa, Mototsugu; Kozuma, Yuka; Matsubara, Taichi; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Shoji, Fumihiro; Oda, Yoshinao; Maehara, Yoshihiko

2017-09-01

Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with anti-PD-1 therapy currently the standard treatment for non-small-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC. We examined PD-L1 expression in NSCLC using the clone SP142 of POPLAR and OAK studies. PD-L1 expression in 499 surgically resected NSCLC patients was evaluated using immunohistochemistry using SP142. We set cutoff values as 1%, 5%, 10%, and 50%. The samples from 189 (37.9%), 119 (23.8%), 71 (14.2%), and 39 (7.8%) patients were positive for PD-L1 expression at cutoff values of 1%, 5%, 10%, and 50%, respectively. Fisher exact tests showed that PD-L1 positivity was significantly associated with male sex, smoking, advanced stage, the presence of vascular invasion, squamous cell carcinoma, and wild type epidermal growth factor receptor gene mutation status at all cutoff values. Univariate and multivariate survival analyses revealed that PD-L1-positive patients had a worse prognosis than PD-L1-negative patients only at the 1% cutoff value. Forest plot analyses showed that the 1% cutoff provided a more sensitive value for the prediction of postoperative prognosis. PD-L1 expression varied greatly according to different cutoff values. This study might be a useful reference to understand the results of POPLAR and OAK studies and to select patients likely to benefit from atezolizumab. Copyright © 2017 Elsevier Inc. All rights reserved.

Interference from retrieval cues in Parkinson's disease.

PubMed

Crescentini, Cristiano; Marin, Dario; Del Missier, Fabio; Biasutti, Emanuele; Shallice, Tim

2011-11-01

Existing studies on memory interference in Parkinson's disease (PD) patients have provided mixed results and it is unknown whether PD patients have problems in overcoming interference from retrieval cues. We investigated this issue by using a part-list cuing paradigm. In this paradigm, after the study of a list of items, the presentation of some of these items as retrieval cues hinders the recall of the remaining ones. We tested PD patients' (n = 19) and control participants' (n = 16) episodic memory in the presence and absence of part-list cues, using initial-letter probes, and following either weak or strong serial associative encoding of list items. Both PD patients and control participants showed a comparable and significant part-list cuing effect after weak associative encoding (13% vs. 12% decrease in retrieval in part-list cuing vs. no part-list cuing -control- conditions in PD patients and control participants, respectively), denoting a similar effect of cue-driven interference in the two populations when a serial retrieval strategy is hard to develop. However, only PD patients showed a significant part-list cuing effect after strong associative encoding (20% vs. 5% decrease in retrieval in patients and controls, respectively). When encoding promotes the development of an effective serial retrieval strategy, the presentation of part-list cues has a specifically disruptive effect in PD patients. This indicates problems in strategic retrieval, probably related to PD patients' increased tendency to rely on external cues. Findings in control conditions suggest that less effective encoding may have contributed to PD patients' memory performance.

Impact of IPDE-SQ personality disorders on the healthcare and societal costs of fibromyalgia patients: a cross-sectional study.

PubMed

Gumà-Uriel, Laura; Peñarrubia-María, M Teresa; Cerdà-Lafont, Marta; Cunillera-Puertolas, Oriol; Almeda-Ortega, Jesús; Fernández-Vergel, Rita; García-Campayo, Javier; Luciano, Juan V

2016-06-01

Data is lacking on comorbid personality disorders (PD) and fibromyalgia syndrome (FMS) in terms of prevalence, and associated healthcare and societal costs. The main aim of this study was to assess the prevalence of PD in FMS patients and to analyse whether the presence of comorbid PD is related to worse functional impairment and greater healthcare (medical visits, drug consumption, and medical tests) and societal costs. A cross-sectional study was performed using the baseline data of 216 FMS patients participating in a randomized, controlled trial carried out in three primary health care centres situated in the region of Barcelona, Spain. Measurement instruments included the International Personality Disorder Examination - Screening Questionnaire (IPDE-SQ), the Fibromyalgia Impact Questionnaire (FIQ), the Client Service Receipt Inventory (CSRI), and a socio-demographic questionnaire. Most patients (65 %) had a potential PD according to the IPDE-SQ. The most prevalent PD were the avoidant (41.4 %), obsessive-compulsive (33.1 %), and borderline (27 %). We found statistically significant differences in functional impairment (FIQ scores) between FMS patients with potential PD vs non-PD (59.2 vs 51.1; p < 0.001). Multivariate regression analyses revealed that higher FIQ total scores and the presence of potential PD were related to more healthcare costs (primary and specialised care visits). As expected, PD are frequent comorbid conditions in patients with FMS. Our results suggest that the screening of comorbid PD in patients with FMS might be recommendable in order to detect potential frequent attenders to primary and specialised care.

Study of telomere length and different markers of oxidative stress in patients with Parkinson's disease.

PubMed

Watfa, G; Dragonas, C; Brosche, T; Dittrich, R; Sieber, C C; Alecu, C; Benetos, A; Nzietchueng, R

2011-04-01

Many studies have shown that short telomere length (TL) is associated with high oxidative stress and various age-related diseases. Parkinson's disease (PD) is an age-related disease, and although its pathogenic mechanism is uncertain, oxidative stress is believed to be implicated in this pathology. The aim of this case-control study was to assess both TL and the different markers of oxidative stress in elderly patients with PD compared to age control subjects. 20 PD patients and 15 age-matched controls, >65 years were studied. TL was measured by Southern blotting from DNA samples extracted from white blood cells. Superoxide dismutase (SOD) activity and plasma levels of total glutathione and protein carbonyls were determined. There was a trend for lower TL in PD patients: 6.06 ± 0.81 kb in PD versus 6.45 ± 0.73 kb in controls (p = 0.08). No significant difference was found between the two groups in terms of oxidative stress markers. In controls, age was the main determinant of telomere shortening (r = -0.547; p = 0.03) whereas, in PD patients, telomere shortening was mainly dependent on plasmatic concentrations of carbonyl proteins (r= -0.544; p=0.044). In PD patients, a negative association was observed between plasma carbonyl protein levels and SOD activity (r= -0.622, p=0.004). In PD, TL is shorter in presence of high oxidative stress as measured by carbonyl protein levels. The absence of telomere attrition with age among patients with PD could reflect a telomere regulation by mechanisms other than age.

Impairments of Speech Fluency in Lewy Body Spectrum Disorder

ERIC Educational Resources Information Center

Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Gunawardena, Delani; Morgan, Brianna; Boller, Ashley; Siderowf, Andrew; Grossman, Murray

2012-01-01

Few studies have examined connected speech in demented and non-demented patients with Parkinson's disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured…

Parkinson's disease psychosis: symptoms, management, and economic burden.

PubMed

Hermanowicz, Neal; Edwards, Kari

2015-08-01

Parkinson’s disease psychosis (PDP) is a costly,debilitating condition that generally develops several years after diagnosis of Parkinson’s disease (PD).PD is the second-most common neurodegenerative disease, and it imposes a significant burden on the healthcare system. Non-motor symptoms commonly manifest in PD, contributing to the severity of a patient’s disability. The neuropsychiatric symptoms that are common in PD can be a significant source of distress to patients and caregivers. Recent studies have shown that more than 50% of patients with PD will develop psychosis at some time over the course of the disease. The responsibility for caring for a person with PDP frequently falls on family members. Caregiver distress is frequently predicted when patients with PD have symptoms of psychosis.Hallucinations and delusions are independent predictors of nursing home placement for patients with PDP. The authors sought to examine total healthcare expenditures among patients with PDP compared with patients with PD without psychosis.All costs were higher for patients with PDP than for those with PD without psychosis and all-Medicare cohorts, with the highest cost differentials found in long-term care costs ($31,178 for PDP vs $14,461 forPD without psychosis), skilled nursing facility costs($6601 for PDP vs $2067 for PD without psychosis),and inpatient costs ($10,125 for PDP vs $6024 for PD without psychosis). Patients with PDP spent an average of 179 days in long-term care, compared with 83 days for patients with PD without psychosis. As expected, long-term care utilization and expenditures were significantly higher for patients with PDP than for patients with PD without psychosis. Reducing long-term care utilization by patients with PDP may significantly lower the overall economic burden associated with PDP.

Encapsulating Peritoneal Sclerosis in Peritoneal Dialysis Patients After Kidney Transplantation.

PubMed

Ayar, Y; Ersoy, A; Ocakoglu, G; Gullulu, E; Kagızmanlı, H; Yıldız, A; Oruc, A; Yavuz, M; Gullulu, M; Dilek, K

Encapsulating peritoneal sclerosis (EPS) is a serious complication for patients with chronic kidney disease (CKD) who were treated with long-term peritoneal dialysis (PD). The risk of EPS was increased after kidney transplantation. In our study we evaluated risk factors for EPS patients after kidney transplantation who were treated before with PD. In our study, between January 2008 and August 2015, 47 PD patients (12 had EPS) who underwent kidney transplantation were analyzed. Age, gender, time of PD treatment, human leukocyte antigen (HLA) matching, cold ischemia time, kidney function (serum urea, creatinine, etc), comorbidities, immunosuppressive therapy, clinical features, and outcomes of PD patients were retrospectively evaluated in both groups. Mean age was 42 (range, 25-60) years in EPS patients, versus 43 (range, 22-77) years without EPS (P = .798). Distribution of gender was similar in both groups (P = .154). The C-reactive protein levels (P < .001), number of patients with peritonitis (P = .001), length of time on PD (P < .001), and serum ferritin levels (P = .020) were higher in EPS patients. The immunosuppressive therapy was changed; tamoxifen and steroids were used after diagnosis in EPS patients. HLA matching was higher in the non-EPS group (P = .006). EPS was more often seen in patients who were treated with continuous ambulatory peritoneal dialysis (CAPD; 75%; P = .036). EPS was more often detected in cadaveric transplant recipients (83.3%; P = .024). High peritoneal transmittance rate was more identified in EPS (+) patients (P = .001). EPS was more often seen in patients who were treated with icodextrin-based regimens in PD before transplantation (91.7%; P = .037). The length of time on PD and high ferritin levels increased EPS 1.08 and 1.01, respectively (P = .036 and .049, respectively), in multivariate analysis. The length of time on PD, type of PD, PD regimens with icodextrin, episodes of peritonitis, and peritoneal transmittance in patients with CKD affect the development of EPS after transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors.

PubMed

Chovanec, Michal; Cierna, Zuzana; Miskovska, Viera; Machalekova, Katarina; Svetlovska, Daniela; Kalavska, Katarina; Rejlekova, Katarina; Spanik, Stanislav; Kajo, Karol; Babal, Pavel; Mardiak, Jozef; Mego, Michal

2017-03-28

Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative in a small subgroup of patients. Previously, we showed that PD-L1 overexpression is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes (TILs) are prognostic in different types of cancer. This study aimed to evaluate the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs. PD-L1 positive TILs were found significantly more often in seminomas (95.9% of patients) and embryonal carcinomas (91.0%) compared to yolk sac tumors (60.0%), choriocarcinomas (54.5%) or teratomas (35.7%) (All p < 0.05). TGCTs patients with high infiltration of PD-L1 positive TILs (HS ≥ 160) had significantly better progression-free survival (HR = 0.17, 95% CI 0.09 - 0.31, p = 0.0006) and overall survival (HR = 0.08, 95% CI 0.04 - 0.16, p = 0.001) opposite to patients with lower expression of PD-L1 (HS < 150). PD-1 expressing TILs were not prognostic in TGCTs. Surgical specimens from 240 patients with primary TGCTs were included into this translational study. The PD-1 and PD-L1 expression on tumor and TILs were detected by immunohistochemistry using anti-PD-1 and anti-PD-L1 monoclonal antibody. Scoring was performed semiquantitatively by weighted histoscore (HS) method. The prognostic value of PD-L1 expressing TILs in TGCTs was demonstrated for the first time.

Survival analysis: comparing peritoneal dialysis and hemodialysis in Taiwan.

PubMed

Huang, Chiu-Ching; Cheng, Kuang-Fu; Wu, Hong-Dar Isaac

2008-06-01

Comparisons of survival in patients on peritoneal dialysis (PD) and on hemodialysis (HD) have been conducted in many Western countries, but publications on this subject in Asian populations are scarce. The present study estimated the survival and the relative mortality hazard for HD and PD patients in Taiwan. Incident end-stage renal disease patients reported to the Taiwan Renal Registry during 1995 - 2002 were included in the study. Patients had to be 20 years of age or older and had to have survived for the first 90 days on dialysis. A total of 45,820 incident HD and 2,809 incident PD patients formed the study population. Patients on PD were treated mainly with traditional glucose-based solutions. Using an intent-to-treat analysis, the Cox proportional hazards (CPH) model was applied to identify the factors that predict survival by treatment modality. Subgroup analyses were conducted by stratifying patients according to sex, comorbidity, age, and diabetes status. Kaplan-Meier estimates were used to explore the survival of HD and PD patients. Adjustments were implemented using the CPH model. The overall 1-year, 2-year, 3-year, 5-year and 10-year survival rates for PD patients were 89.8%, 77.6%, 67.6%, 55.5%, and 35% respectively. The equivalent survival rates for HD patients were 87.5%, 76.6%, 68.1%, 54.3%, and 33.8%. The differences were not statistically significant (p = 0.125). The CPH analysis stratified by diabetes status and age revealed that PD patients 55 years of age or younger and nondiabetic had a lower mortality ratio (MR) of 0.94. But the MR increased to 1.31 for nondiabetic patients older than 55. The MR for PD versus HD further increased to 1.72 for diabetic patients 55 years of age or younger, and to 1.99 for diabetic patients older than 55. After adjusting for both demographic and clinical case-mix differences, PD and HD patients were observed to have similar long-term survival. Subgroup analyses revealed that, among diabetic patients and patients older than 55, those on HD experienced better survival than did those on PD.

Differentiating Patients with Parkinson's Disease from Normal Controls Using Gray Matter in the Cerebellum.

PubMed

Zeng, Ling-Li; Xie, Liang; Shen, Hui; Luo, Zhiguo; Fang, Peng; Hou, Yanan; Tang, Beisha; Wu, Tao; Hu, Dewen

2017-02-01

Parkinson's disease (PD) is one of the most common neurodegenerative disorders in the world. Previous studies have focused on the basal ganglia and cerebral cortices. To date, the cerebellum has not been systematically investigated in patients with PD. In the current study, 45 probable PD patients and 40 age- and gender-matched healthy controls underwent structural magnetic resonance imaging, and we used support vector machines combining with voxel-based morphometry to explore the cerebellar structural changes in the probable PD patients relative to healthy controls. The results revealed that the gray matter alterations were primarily located within the cerebellar Crus I, implying a possible important role of this region in PD. Furthermore, the gray matter alterations in the cerebellum could differentiate the probable PD patients from healthy controls with accuracies of more than 95 % (p < 0.001, permutation test) via cross-validation, suggesting the potential of analyzing the cerebellum in the clinical diagnosis of PD.

Personality and Parkinson's disease: A meta-analysis.

PubMed

Santangelo, Gabriella; Garramone, Federica; Baiano, Chiara; D'Iorio, Alfonsina; Piscopo, Fausta; Raimo, Simona; Vitale, Carmine

2018-04-01

Personality changes are considered pre-motor features of Parkinson's disease (PD). Cross-sectional studies revealed that PD patients were more introvert, apprehensive, and cautious than healthy subjects (HS), whereas other studies failed to disclose these behavioural traits. Some studies found mixed results concerning Novelty Seeking (NS) and Harm Avoidance (HA) profiles in PD patients. To better clarify the personality profile in PD we performed a meta-analysis on studies exploring such topic according to both Cloninger's Psychobiological Model (PM) and Big Five Model (BFM) METHODS: The meta-analysis included 17 studies evaluating the personality in PD patients compared with HS. The outcomes were the dimensions of the temperament and character of the PM and personality traits of BFM. Effect sizes from data reported in the primary studies were computed using Hedges'g unbiased approach. Heterogeneity among the studies and publication bias were assessed. Meta-regressions were conducted with age at evaluation, gender, schooling, and type of personality trait tools as moderators. As for PM, PD patients scored higher on HA and lower on NS than HS. No difference was found on Reward Dependence, Perseverance/Persistence and on character level. As for BFM, higher levels of Neuroticism, but lower levels of Openness and Extraversion were associated with PD. The personality profile in PD is characterized by high Neuroticism and HA, and by low Openness, Extraversion and NS. The personality profile delineated in the present study on PD patients seems to reflect the premorbid one and might contribute to development and persistence of affective disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Altered Pharyngeal Muscles in Parkinson Disease

PubMed Central

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Samanta, Johan E.; Beach, Thomas G.

2012-01-01

Dysphagia (impaired swallowing) is common in Parkinson disease (PD) patients and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor (PC) and cricopharyngeal (CP) sphincter muscles in postmortem specimens from 8 PD and 4 age-matched control patients. Pharyngeal muscles in PD patients exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, the PD patients with dysphagia had a higher percentage of atrophic myofibers vs. with those without dysphagia and controls. The fast-to-slow fiber type transition is consistent with abnormalities in swallowing, slow movement of food and increased tone in the CP sphincter in PD patients. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in PD patients. PMID:22588389

Pain Correlates with Sleep Disturbances in Parkinson's Disease Patients.

PubMed

Fu, Yun-Ting; Mao, Cheng-Jie; Ma, Li-Jing; Zhang, Hui-Jun; Wang, Yi; Li, Jie; Huang, Jun-Ying; Liu, Jun-Yi; Liu, Chun-Feng

2018-01-01

Both sleep disorders and pain decrease quality of life in patients with Parkinson's disease (PD). However, little is known about the relationship between objective sleep disturbances and pain in patients with PD. This study aimed to (1) examine the clinical characteristics of pain in PD patients and (2) explore the correlation between pain and sleep disturbances in PD patients. Parkinson's disease patients (N = 144) underwent extensive clinical evaluations of motor and nonmotor symptoms and characteristics of pain. Overnight video-polysomnography was also conducted. Clinical characteristics and sleep parameters were compared between PD patients with or without pain. Pain was reported by 75 patients (52.1%), with 49 (65.3%) reporting pain of at least moderate severity. PD patients with pain were older and had longer disease duration, more severe PD symptoms as assessed by Hoehn and Yahr stage and the Unified Parkinson's Disease Rating Scale, and higher L-dopa equivalent daily dose compared with PD patients without pain. PD patients with pain also showed significantly decreased sleep efficiency (57.06% ± 15.84% vs. 73.80% ± 12.00%, P < 0.001), increased nonrapid eye movement stage 1 (N1) sleep (33.38% ± 19.32% vs. 17.84% ± 8.48%, P < 0.001), and decreased rapid eye movement sleep (12.76% ± 8.24% vs. 16.06% ± 6.53%, P = 0.009). Binary logistic regression analysis revealed that poorer activities of daily living, depressed mood, higher percentage of N1 sleep, and lower sleep efficiency were independent predictors of pain in patients with PD. Musculoskeletal pain is the most common type of pain in patients with PD. Disrupted sleep continuity, altered sleep architecture, depressed mood, and compromised activities of daily living may be associated with pain in patients with PD. © 2017 World Institute of Pain.

Pathological Gambling in Parkinson's disease patients: Dopaminergic medication or personality traits fault?

PubMed

Brusa, L; Pavino, V; Massimetti, M C; Ceravolo, R; Stefani, S; Stanzione, P

2016-07-15

Impulse control disorders (ICDs) are clinically relevant in Parkinson disease (PD) patients, with an established association with PD medication. Aim of our study was to study whether the increased frequency of pathological gambling (PG), reported in subgroups of PD patients, is related to specific personality tracts additional to dopaminergic medications. Thirty-seven PD patients with a personal history of PG where enrolled. Twenty one PD patients, matched for disease and dopaminergic therapy, never experiencing PG, were enrolled as controls. All subjects were tested with the Minnesota Multiphasic Inventory Personality scales (MMPI-2). Our data showed that PD group with PG exhibited significantly higher mean values of the three validity scales in comparison to the non-PG-PD group, demonstrating an higher tendency to lie. Content scales showed a significant increase of cynicism and bizarre ideation scales score in the PG-PD group, not exhibiting pathological values at the validity scales, (p: 0.02) in comparison to non-PG PD patients. According to our results, PG seems to be associated with precise personality tracts. Personality profiles of cluster A personality disturbances - Axys 2 according with DSM-5 TR (paranoid type) at MMPI-2 might be a warning index helpful in selecting dopaminergic treatment, to avoid subsequent ICDs appearance. Copyright © 2016 Elsevier B.V. All rights reserved.

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma.

PubMed

Fang, Xia; Xiu, Bing; Yang, Zhizhang; Qiu, Weizhe; Zhang, Long; Zhang, Suxia; Wu, Yunjin; Zhu, Xuyou; Chen, Xue; Xie, Suhong; Yi, Xianghua; Liang, Aibin; Zeng, Yu

2017-04-01

Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan-Meier curves with log rank test, and Cox's proportional hazards regression model.PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients' gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1 TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients' survival time. Besides, PD-1 expression, patients' age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance.PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.

Effluent CA 125 concentration in chronic peritoneal dialysis patients: influence of PD duration, peritoneal transport and PD regimen.

PubMed

Fusshöller, Andreas; Grabensee, Bernd; Plum, Jörg

2003-01-01

In terms of the integrity of the peritoneal membrane in peritoneal dialysis (PD), the peritoneal mesothelial cells play a pivotal role since its monolayer constitutes the first line of the peritoneal membrane. Cancer antigen 125 (CA 125) is released by peritoneal mesothelial cells and correlates with the mesothelial cell mass in PD. Since its effluent concentration is easy to determine in chronic PD patients, CA 125 serves as an in vivo marker of biocompatibility. We performed a cross-sectional study to investigate the relation between PD duration, peritoneal transport and the PD regimen (CAPD/CCPD) on effluent CA 125 concentration in 22 chronic PD patients. We compared long-term (>6 months) with short-term PD treatment, patients with high small solute transport properties (MTAC >11 ml/min, d/p ratio of creatinine >0.72) to patients with low small solute transport and CAPD with APD patients. A peritoneal equilibration test was performed with 1.36% glucose. Dialysate/plasma (D/P) ratio and mass transfer area coefficient (MTAC) of creatinine were calculated and the 4-hour effluent concentration of CA 125 was determined. CA 125 tended to be lower in the long-term PD patients and also in APD patients, but statistical significance was missing. Effluent CA 125 was significantly increased in patients with an MTAC of creatinine >11 ml/min (40.2 +/- 11.2 vs. 20.7 +/- 1.2 U/ml) and in patients with a d/p ratio of creatinine >0.72 (48.2 +/- 11.0 vs. 21.6 +/- 1.6 U/ml). CA 125 and the d/p ratio of creatinine were positively correlated (r = 0.68). The positive correlation of CA 125 with peritoneal small solute transport especially in the early phase of PD treatment indicates an initial correlation of the mesothelial cell mass with the peritoneal surface area. A direct relation between the CA 125 concentration and peritoneal transport is unlikely. In our study the CA 125 effluent concentration tended to be lower in long-term PD patients and also in APD patients, possibly indicating a cell depletory influence of the conventional PD fluid. Copyright 2003 S. Karger AG, Basel

Differential performance on tasks of affective processing and decision-making in patients with Panic Disorder and Panic Disorder with comorbid Major Depressive Disorder.

PubMed

Kaplan, Johanna S; Erickson, Kristine; Luckenbaugh, David A; Weiland-Fiedler, Petra; Geraci, Marilla; Sahakian, Barbara J; Charney, Dennis; Drevets, Wayne C; Neumeister, Alexander

2006-10-01

Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychological function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological functioning in patients with PD and PD + MDD by focusing on tasks that assess attention, psychomotor speed, executive function, decision-making, and affective processing. Twenty-two unmedicated patients with PD, eleven of whom had a secondary diagnosis of MDD, were compared to twenty-two healthy controls, matched for gender, age, and intelligence on tasks of attention, memory, psychomotor speed, executive function, decision-making, and affective processing from the Cambridge Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and Affective Go/No-go Task. Relative to matched healthy controls, patients with PD + MDD displayed an attentional bias toward negatively-valenced verbal stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of memory and visual discrimination compared to their controls. In contrast, no group differences were found for PD patients relative to matched control subjects. The sample size was limited, however, all patients were drug-free at the time of testing. The PD + MDD patients demonstrated deficits on a task involving visual discrimination and working memory, and an attentional bias towards negatively-valenced stimuli. In addition, patients with comorbid depression provided qualitatively different responses in the areas of affective and decision-making processes.

Dysphagia in Parkinson's disease.

PubMed

Hisashi, Shinobu; Fukumitsu, Ryoko; Ishida, Mitsuyo; Nodera, Atsuko; Otani, Takahiro; Maruoka, Takahiro; Nakamura, Kazumi; Izumi, Yuishin; Kaji, Ryuji; Nishida, Yoshihiko

2016-08-31

Although dysphagia is an important symptom associated with prognosis in patients with Parkinson's disease (PD), dysphagia tends to be overlooked until swallowing difficulties reach an advanced phase. We assessed dysphagia with videofluoroscopic examination of swallowing in 31 patients with mainly mild or moderate PD. Swallowing problems were observed in the pharyngeal phase in 28 patients, oral phase in 19 patients, esophageal phase in 15 patients, and oral preparatory phase in 1 patient. Therefore, dysphagia in the pharyngeal phase was observed in almost all patients with mild or moderate PD. In contrast, no dysfunction was detected in most patients when screening was conducted via questionnaire or other methods. Assessment of clinical parameters in the present study suggests that latent swallowing dysfunction may be present even in the early disease stage in PD. A future prospective study to follow swallowing functions in a pre-symptomatic phase in PD would be fruitful to find whether swallowing dysfunction is one of the prodromal symptoms.

Health policies on dialysis modality selection: a nationwide population cohort study

PubMed Central

Lin, Yi-Chun; Lin, Yen-Chung; Kao, Chih-Chin; Chen, Hsi-Hsien; Hsu, Chih-Cheng; Wu, Mai-Szu

2017-01-01

Objectives In Taiwan, peritoneal dialysis (PD) and haemodialysis are fully accessible to patients with end-stage renal disease. However, the usage of PD is considered low in Taiwan. Since 2005, 4 major policies have been implemented by Taiwan's Ministry of Health and Welfare, namely a multidisciplinary predialysis care programme and usage increasing the PD incidence as a key performance indicator (KPI) for hospital accreditation, both of which were implemented in 2006; reimbursement of the glucose-free dialysate, icodextrin that was implemented in 2007; and insurance reimbursement for renting automated PD machines that was implemented in 2008. The aim of this study was to analyse the associations between the PD promotional policies and the actual PD selection rates. Setting We analysed data within the Taiwan Renal Registry Data System from 2006 to 2013, focusing on the PD incidence in relation to the timings of the 4 PD promotional policies; then we stratified the results according to age, sex and the presence of diabetes mellitus. Participants From 2006 to 2013, 115 565 patients were enrolled in this study. The mean (SD) age of patients on PD was 54.6 (15.7) years. Results During the time frame in which the 4 PD promotional policies were implemented, the PD incidence increased from 12.8% in 2006 to 15.1% in 2009. The PD incidence started to decline in 2010 (13.8%) when the hospital accreditation policy was repealed. The 3 remaining policies were weakly associated with the PD incidence. The observational analysis determined that the patients' ages, sexes and diabetes mellitus incidence rates were relatively stable from 2006 to 2013. Conclusions Of the 4 health policies intended to promote PD usage, using increasing the PD incidence as a KPI for hospital accreditation had the strongest association with the PD incidence. PMID:28077410

Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study.

PubMed

Hagag, Adel A; Badraia, Ibrahim M; Elfarargy, Mohamed S; Abd Elmageed, Mohamed M; Abo-Ali, Ehab A

2018-02-13

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide that causes a spectrum of diseases including neonatal hyperbilirubinemia, acute and chronic hemolysis after exposure to oxidative stress. This five years retrospective study was carried out to study the demographic, clinical and laboratory data of 1000 patients with G6PD deficiency anemia registered in Hematology Unit, Pediatric Department, Tanta University Hospital. Data were collected from patient's files, from November 2011 to November 2016, using the pre-designed questionnaires to obtain the complete history, clinical presentation and laboratory investigations including the complete blood count, red blood cells morphology, liver and renal functions and quantitative assay of G6PD enzyme activity by spectrophotometric method. Males were more commonly affected than females (932 males versus 68 females). The highest prevalence of hemolytic crisis in G6PD deficiency patients was found within the age group of 1-3 years (920 patients; 92%) with mean age of the first presentation of 22.8±15.54 months. Patients presented mainly with pallor (1000 patients; 100%), dark red urine (896 patients; 89.6%) and jaundice (878 patients; 87.8%) after 24-72 hours of exposure to the precipitating factors (mean: 36±17.73 hours). Diets were the most common precipitating factor of hemolysis in patients with G6PD deficiency (834 patients; 83.4% of studied cases) especially fava beans (326 patients; 32.6%) and falafel (194 patients; 19.4%) which were the most common precipitating food products causing hemolysis followed by chick pea (108 patients; 10.8%), broad bean (76 patients; 7.6%), green pea (44 patients; 4.4%), pea nuts (38 patients; 3.8%), lentil (28 patients; 2.8%), and lastly black eyed peas (20 patients; 2 %). Infections were the 2nd most common cause of hemolysis (124 patients; 12.4%) including pneumonia (34 patients; 3.4%), tonsillitis (32 patients; 3.2%), typhoid fever (28 patients; 2.8%), hepatitis A (18 patients; 1.8%) and urinary tract infection (12 patients; 1.2%). Drugs were the least common cause of hemolysis (42 patients; 4.2%) including diclofenac sodium (24 patients; 2.4%), ibuprofen (8 patients; 0.8%), acetylsalicylic acid (4 patients; 0.4%), co-trimoxazole (4 patients; 0.4%) and nitrofurantion (2 patients; 0.2%). There was normocytic normochromic anemia with reticulocytosis and Heinz bodies in pre-transfusion complete blood picture in all studied cases. G6PD assay show marked decrease in enzyme level at time of presentation in all cases with the commonest G6PD enzyme level of 3-4 U/gm Hb (592 patients; 59.2%). G6PD deficiency anemia presented mainly with pallor, dark red urine and jaundice after exposure to certain diets, drugs and diseases and therefore patients with G6PD deficiency should avoid exposure to these precipitating factors of hemolysis. We can also recommend large neonatal screening programs to detect cases of G6PD deficiency before the occurrence of acute hemolysis and molecular studies to detect G6PD enzyme variant in Egypt. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Clinical Activity of PD-1/PD-L1 inhibitors in Metastatic Non-Clear Cell Renal Cell Carcinoma.

PubMed

McKay, Rana R; Bossé, Dominick; Xie, Wanling; Wankowicz, Stephanie A M; Flaifel, Abdallah; Brandao, Raphael; Lalani, Aly-Khan; Martini, Dylan J; Wei, Xiao X; Braun, David A; Van Allen, Eliezer M; Castellano, Daniel; de Velasco, Guillermo; Wells, J Connor; Heng, Daniel Y C; Fay, Andre P; Schutz, Fabio A; Hsu, JoAnn; Pal, Sumanta Kumar; Lee, Jae-Lyun; Hsieh, James; Harshman, Lauren C; Signoretti, Sabina; Motzer, Robert J; Feldman, Darren R; Choueiri, Toni K

2018-05-10

Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non-clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation is limited. In this multicenter analysis, we explored the efficacy of PD-1/PD-L1 inhibitors in patients with nccRCC or sarcomatoid/rhabdoid differentiation. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate. Secondary endpoints include time-to-treatment failure (TTF), overall survival (OS), and biomarker correlates. Forty-three patients were included: papillary (n = 14; 33%), chromophobe (n = 10; 23%), unclassified (n = 9; 21%), translocation (n = 3; 7%), and ccRCC with sarcomatoid differentiation (n = 7, 16%). Of those 43 patients, 11 patients (26%) had sarcomatoid and/or rhabdoid differentiation (n = 7 with ccRCC; n = 4 nccRCC). Overall, eight patients (19%) objectively responded, including four patients (13%) who received PD-1/PD-L1 monotherapy. Responses were observed in patients with ccRCC with sarcomatoid and/or rhabdoid differentiation (n = 3/7, 43%), translocation RCC (n = 1/3, 33%), and papillary RCC (n = 4/14, 29%). The median TTF was 4.0 months (95% confidence interval (CI) 2.8, 5.5) and median OS was 12.9 months (95% CI 7.4, not reached). No specific genomic alteration was associated with clinical benefit. Modest antitumor activity for PD-1/PD-L1 blocking agents was observed in some patients with nccRCC. Further prospective studies are warranted to investigate the efficacy of PD-1/PD-L1 blockade in this heterogeneous patient population. Copyright ©2018, American Association for Cancer Research.

Temperament, character and anxiety sensitivity in panic disorder: a high-risk study.

PubMed

Perna, Giampaolo; di Pasquale, Danila; Grassi, Massimiliano; Vanni, Giovanna; Bellodi, Laura; Caldirola, Daniela

2012-01-01

Adult patients with panic disorder (PD) show high levels of harm avoidance and anxiety sensitivity. Peculiar temperament profiles and high anxiety sensitivity have been proposed as developmental risk factors for PD in adult age. Since familial-genetic influences play a role both in PD and in anxiety sensitivity and temperament profiles, this study aims to investigate the possible association between family history of PD and peculiar temperament-character profiles or high anxiety sensitivity in offspring of patients with PD. Thirty-four children of patients with PD with/without agoraphobia and 30 children of healthy subjects were compared. Temperament and character dimensions and anxiety sensitivity levels of children were obtained by the Junior Temperament and Character Inventory and the Childhood Anxiety Sensitivity Index. Children of patients with PD and children of healthy subjects differed neither in temperament and character dimensions nor in anxiety sensitivity levels. Our results show that family history of PD is not associated with peculiar temperament and character profiles or high anxiety sensitivity in children, suggesting that these factors may not be early expressions of familial vulnerability to PD. Since the sample is small and the study has a cross-sectional design, longitudinal studies in larger samples are warranted to confirm these findings and to clarify the role of anxiety sensitivity and temperament-character dimensions in the development of PD. Copyright © 2012 S. Karger AG, Basel.

Fragmented sleep: an unrevealed problem in peritoneal dialysis patients.

PubMed

Yngman-Uhlin, Pia; Johansson, Anna; Fernström, Anders; Börjeson, Sussanne; Edéll-Gustafsson, Ulla

2011-04-01

The aim of this study was to describe the sleep-wake cycle, sleep quality, fatigue and Health Related Quality of Life (HRQoL) measured with questionnaires, actigraphy and a sleep diary during a one-week period in patients undergoing peritoneal dialysis (PD) treatment at home. A further aim was to explore differences compared with patients with coronary artery disease (CAD) and individuals from the general population. In this study one-week actigraphy registration, four questionnaires (Uppsala Sleep Inventory, SF-36, FACIT-fatigue, International Restless Legs Study Groups' form) and a sleep diary were used. Data from 68 participants and 470 nights were collected. PD patients (n = 28) had more fragmented sleep (p < 0.001) and worse sleep efficiency (SE%) (p < 0.0001) than the CAD (n = 22) and the population (n = 18) groups. Pruritus (57%), restless legs (46%) and fatigue (89%) were prevalent in PD patients. Pruritus correlated with fragmented sleep (r = -0.45, p = 0.01) and SE (r = -0.49, p = 0.01). In HRQoL, the physical component score was decreased in the PD and CAD groups (p < 0.01) compared to the population group. To the authors' knowledge this study is the first to demonstrate that PD patients have deteriorated sleep, with serious fragmentation measured by a one-week actigraphy registration. Further, PD patients exhibit worse sleep quality than CAD patients and individuals in the population. Evaluation of sleep in clinical practice is highly recommended since PD patients are vulnerable individuals with extended self-care responsibilities and at risk for comorbidity secondary to insufficient sleep. Future research on whether PD patients' sleep problems and fatigue can be improved by an individual non-pharmacological intervention programme is required.

Gender-based analysis of cortical thickness and structural connectivity in Parkinson's disease.

PubMed

Yadav, Santosh K; Kathiresan, Nagarajan; Mohan, Suyash; Vasileiou, Georgia; Singh, Anup; Kaura, Deepak; Melhem, Elias R; Gupta, Rakesh K; Wang, Ena; Marincola, Francesco M; Borthakur, Arijitt; Haris, Mohammad

2016-11-01

Parkinson's disease (PD) is a progressive neurological disorder and appears to have gender-specific symptoms. Studies have observed a higher frequency for development of PD in male than in female. In the current study, we evaluated the gender-based changes in cortical thickness and structural connectivity in PD patients. With informed consent, 64 PD (43 males and 21 females) patients, and 46 (12 males and 34 females) age-matched controls underwent clinical assessment including Mini-Mental State Examination (MMSE) and magnetic resonance imaging on a 1.5 Tesla clinical MR scanner. Whole brain high-resolution T1-weighted images were acquired from all subjects and used to measure cortical thickness and structural network connectivity. No significant difference in MMSE score was observed between male and female both in control and PD subjects. Male PD patients showed significantly reduced cortical thickness in multiple brain regions including frontal, parietal, temporal, and occipital lobes as compared with those in female PD patients. The graph theory-based network analysis depicted lower connection strengths, lower clustering coefficients, and altered network hubs in PD male than in PD female. Male-specific cortical thickness changes and altered connectivity in PD patients may derive from behavioral, physiological, environmental, and genetical differences between male and female, and may have significant implications in diagnosing and treating PD among genders.

Multiscale entropy analysis of electroencephalography during sleep in patients with Parkinson disease.

PubMed

Chung, Chen-Chih; Kang, Jiunn-Horng; Yuan, Rey-Yue; Wu, Dean; Chen, Chih-Chung; Chi, Nai-Fang; Chen, Po-Chih; Hu, Chaur-Jong

2013-07-01

Sleep disorders are frequently seen in patients with Parkinson disease (PD), including rapid eye movement (REM) behavior disorder and periodic limb movement disorder. However, knowledge about changes in non-REM sleep in patients with PD is limited. This study explored the characteristics of electroencephalography (EEG) during sleep in patients with PD and non-PD controls. We further conducted multiscale entropy (MSE) analysis to evaluate and compare the complexity of sleep EEG for the 2 groups. There were 9 patients with PD (Hoehn-Yahr stage 1 or 2) and 11 non-PD controls. All participants underwent standard whole-night polysomnography (PSG), which included 23 channels, 6 of which were for EEG. The raw data of the EEG were extracted and subjected to MSE analysis. Patients with PD had a longer sleep onset time and a higher spontaneous EEG arousal index. Sleep stage-specific increased MSE was observed in patients with PD during non-REM sleep. The difference was more marked and significant at higher time scale factors (TSFs). In conclusion, increased biosignal complexity, as revealed by MSE analysis, was found in patients with PD during non-REM sleep at high TSFs. This finding might reflect a compensatory mechanism for early defects in neuronal network control machinery in PD.

"Biocompatible" Neutral pH Low-GDP Peritoneal Dialysis Solutions: Much Ado About Nothing?

PubMed

Misra, Paraish S; Nessim, Sharon J; Perl, Jeffrey

2017-03-01

Adverse outcomes in peritoneal dialysis (PD), including PD related infections, the loss of residual kidney function (RKF), and longitudinal, deleterious changes in peritoneal membrane function continue to limit the long-term success of PD therapy. The observation that these deleterious changes occur upon exposure to conventional glucose-based PD solutions fuels the search for a more biocompatible PD solution. The development of a novel PD solution with a neutral pH, and lower in glucose degradation products (GDPs) compared to its conventional predecessors has been labeled a "biocompatible" solution. While considerable evidence in support of these novel solutions' biocompatibility has emerged from cell culture and animal studies, the clinical benefits as compared to conventional PD solutions are less clear. Neutral pH low GDP (NpHLGDP) PD solutions appear to be effective in reducing infusion pain, but their effects on other clinical endpoints including peritoneal membrane function, preservation of RKF, PD-related infections, and technique and patient survival are less clear. The literature is limited by studies characterized by relatively few patients, short follow-up time, heterogeneity with regards to the novel PD solution type under study, and the different patient populations under study. Nonetheless, the search for a more biocompatible PD solution continues with emerging data on promising non glucose-based solutions. © 2017 Wiley Periodicals, Inc.

Parkinson's disease with mild cognitive impairment: severe cortical thinning antedates dementia.

PubMed

Gasca-Salas, Carmen; García-Lorenzo, Daniel; Garcia-Garcia, David; Clavero, Pedro; Obeso, José A; Lehericy, Stephane; Rodríguez-Oroz, María C

2017-07-14

Mild cognitive impairment (MCI) in Parkinson's disease (PD) is a risk factor for dementia and thus, it is of interest to elucidate if specific patterns of atrophy in PD-MCI patients are associated with a higher risk of developing dementia. We aim to define pattern(s) of regional atrophy in PD-MCI patients who developed dementia during 31 months of follow-up using cortical thickness analysis Twenty-three PD-MCI patients and 18 controls underwent brain MRI and completed a neuropsychological examination at baseline, PD-MCI patients were followed after a 31 month follow-up in order to assess their progression to dementia. At follow up, 8 PD-MCI patients had converted to dementia (PD-MCI converters) whereas 15 remained as PD-MCI (PD-MCI non-converters). All patients were at least 60 years old and suffered PD ≥ 10 years. There were no baseline differences between the two groups of patients in clinical and neuropsychological variables. The cortex of PD-MCI converters was thinner than that of PD-MCI non-converters, bilaterally in the frontal, insula and the left middle temporal areas, also displaying a more widespread pattern of cortical thinning relative to the controls. This study shows that aged and long-term PD patients with MCI who convert to dementia in the short-mid term suffer a thinning of the cortex in several areas (frontal cortex, and middle temporal lobe and insula), even when their cognitive impairment was similar to that of PD-MCI non-converters. Thus, MRI analysis of cortical thickness may represent a useful measure to identify PD-MCI patients at a higher risk of developing dementia.

Programmed Death Cell Ligand 1 (PD-L1) Is Associated With Survival in Stage I Non-Small Cell Lung Cancer.

PubMed

Sepesi, Boris; Cuentas, Edwin Parra; Canales, Jaime Rodriguez; Behrens, Carmen; Correa, Arlene M; Vaporciyan, Ara; Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar; Swisher, Stephen; Wistuba, Ignacio

2017-01-01

Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis. Statistics included recursive partitioning, univariable, multivariable, and Kaplan-Meier analyses. Patients whose tumors expressed <4.7% PD-L1 (N = 87) experienced significantly better overall survival (OS) (P = 0.001) than patients with PD-L1 >4.7% (N = 26). Patients with PD-L1 expression in macrophages <6.3% (N = 24) also experienced significantly better (P = 0.005) OS than patients with >6.3% (N = 89). The best outcomes were observed in patients with low PD-L1 expression in both tumor and macrophages with 5-year OS of 94% (N = 17). Contrarily, patients with high PD-L1 expression in both tumor and macrophages experienced 5-year OS of 20% (N = 19). Low PD-L1 expression in the tumor and in the TIMs was independently associated with survival in multivariable analysis (P = 0.000 and P = 0.030, respectively). Lower PD-L1 % expression in the tumor and in the TIMs seems to be associated with significantly better OS in surgically resected stage I lung cancer. Additional studies are needed to validate PD-L1 as a prognostic biomarker in lung cancer and to study the mechanisms of intratumoral immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

Erectile function profiles in men with Peyronie's disease.

PubMed

Deveci, Serkan; Palese, Michael; Parker, Marilyn; Guhring, Patricia; Mulhall, John P

2006-05-01

In this study we investigated the erectile function status of men presenting with Peyronie's disease. Demographics of patients regarding age, duration of PD, nature of deformity and comorbidities were compared between the patients with PD, with and without erectile dysfunction. Patients with erectile dysfunction underwent dynamic infusion cavernosometry/cavernosography. The hemodynamic profile of patients presenting with combined PD and ED were analyzed and compared between those with onset of ED before and after diagnosis of PD. Of the 222 patients 78 had ED (35%) by self-report at presentation. The mean age of patients with PD and ED was 52 +/- 22 years old. Hypertension (71.5%), hyperlipidemia (60.4%) and smoking (49.2%) were the leading comorbidities in the entire group. Statistically significant differences were found between the groups with and without ED for hypertension (p = 0.02) and cigarette smoking (p = 0.009). Of 222 patients 45 (20%) had ED that predated PD onset (group 1) and 33 (15%) had ED that postdated the onset of PD (group 2). DICC showed normal hemodynamics in 14 of 78 patients (18%), arteriogenic insufficiency in 50 (64%) and corporoveno-occlusive dysfunction in 16 (20%). CVOD was evenly distributed between groups 1 and 2, whereas arteriogenic ED was significantly higher in group 1 (82%). Site specific leak was seen in 4 of 33 (12%), all group 2 patients. Patients in whom ED postdates the onset of PD are more likely to have normal erectile hemodynamics. Site specific leak is an uncommon contributor to PD and is seen only in the patients with PD in whom ED postdated PD onset. The leading vascular etiology of ED in PD is arteriogenic in older patients and those with greater associated comorbidities.

Quality of life in patients on chronic dialysis in South Africa: a comparative mixed methods study.

PubMed

Tannor, Elliot K; Archer, Elize; Kapembwa, Kenneth; van Schalkwyk, Susan C; Davids, M Razeen

2017-01-05

The increasing prevalence of treated end-stage renal disease and low transplant rates in Africa leads to longer durations on dialysis. Dialysis should not only be aimed at prolonging lives but also improve quality of life (QOL). Using mixed methods, we investigated the QOL of patients on chronic haemodialysis (HD) and peritoneal dialysis (PD). We conducted a cross-sectional study at Tygerberg Hospital in Cape Town, South Africa. All the PD patients were being treated with continuous ambulatory peritoneal dialysis. The KDQOL-SF 1.3 questionnaire was used for the quantitative phase of the study. Thereafter, focus-group interviews were conducted by an experienced facilitator in groups of HD and PD patients. Electronic recordings were transcribed verbatim and analysed manually to identify emerging themes. A total of 106 patients completed questionnaires and 36 of them participated in the focus group interviews. There was no difference between PD and HD patients in the overall KDQOL-SF scores. PD patients scored lower with regard to symptoms (P = 0.005), energy/fatigue (P = 0.025) and sleep (P = 0.023) but scored higher for work status (P = 0.005) and dialysis staff encouragement (P = 0.019) than those on HD. Symptoms and complications were verbalised more in the PD patients, with fear of peritonitis keeping some housebound. PD patients were more limited by their treatment modality which impacted on body image, sexual function and social interaction but there were less dietary and occupational limitations. Patients on each modality acknowledged the support received from family and dialysis staff but highlighted the lack of support from government. PD patients had little opportunity for interaction with one another and therefore enjoyed less support from fellow patients. PD patients experienced a heavier symptom burden and greater limitations related to their dialysis modality, especially with regards to social functioning. The mixed-methods approach helped to identify several issues affecting quality of life which are amenable to intervention.

Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset.

PubMed

Nichols, W C; Pankratz, N; Marek, D K; Pauciulo, M W; Elsaesser, V E; Halter, C A; Rudolph, A; Wojcieszek, J; Pfeiffer, R F; Foroud, T

2009-01-27

To characterize sequence variation within the glucocerebrosidase (GBA) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease. We performed a comprehensive study of all GBA exons in one patient with PD from each of 96 PD families, selected based on the family-specific lod scores at the GBA locus. Identified GBA variants were subsequently screened in all 1325 PD cases from 566 multiplex PD families and in 359 controls. Nine different GBA variants, five previously reported, were identified in 21 of the 96 PD cases sequenced. Screening for these variants in the full sample identified 161 variant carriers (12.2%) in 99 different PD families. An unbiased estimate of the frequency of the five previously reported GBA variants in the familial PD sample was 12.6% and in the control sample was 5.3% (odds ratio 2.6; 95% confidence interval 1.5-4.4). Presence of a GBA variant was associated with an earlier age at onset (p = 0.0001). On average, those patients carrying a GBA variant had onset with PD 6.04 years earlier than those without a GBA variant. This study suggests that GBA is a susceptibility gene for familial Parkinson disease (PD) and patients with GBA variants have an earlier age at onset than patients with PD without GBA variants.

Brain iron concentrations in regions of interest and relation with serum iron levels in Parkinson disease.

PubMed

Costa-Mallen, Paola; Gatenby, Christopher; Friend, Sally; Maravilla, Kenneth R; Hu, Shu-Ching; Cain, Kevin C; Agarwal, Pinky; Anzai, Yoshimi

2017-07-15

Brain iron has been previously found elevated in the substantia nigra pars compacta (SNpc), but not in other brain regions, of Parkinson's disease (PD) patients. However, iron in circulation has been recently observed to be lower than normal in PD patients. The regional selectivity of iron deposition in brain as well as the relationship between SNpc brain iron and serum iron within PD patients has not been completely elucidated. In this pilot study we measured brain iron in six regions of interest (ROIs) as well as serum iron and serum ferritin, in 24 PD patients and 27 age- gender-matched controls. Brain iron was measured on magnetic resonance imaging (MRI) with a T2 prime (T2') method. Difference in brain iron deposition between PD cases and controls for the six ROIs were calculated. SNpc/white matter brain iron ratios and SNpc/serum iron ratios were calculated for each study participant, and differences between PD patients and controls were tested. PD patients overall had higher brain iron than controls in the SNpc. PD patients had significantly higher SNpc/white matter brain iron ratios than controls, and significantly higher brain SNpc iron/serum iron ratios than controls. These results indicate that PD patients' iron metabolism is disrupted toward a higher partitioning of iron to the brain SNpc at the expenses of iron in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Hemodialysis and peritoneal dialysis are associated with similar outcomes for end-stage renal disease treatment in Canada.

PubMed

Yeates, Karen; Zhu, Naisu; Vonesh, Edward; Trpeski, Lilyanna; Blake, Peter; Fenton, Stanley

2012-09-01

There were 35 265 patients receiving renal replacement therapy in Canada at the end of 2007 with 11.0% of patients on peritoneal dialysis (PD) and 48.9% on hemodialysis (HD) and a remaining 40.1% living with a functioning kidney transplant. There are no contemporary studies examining PD survival relative to HD in Canada. The objective was to compare survival outcomes for incident patients starting on PD as compared to HD in Canada. Using data from the Canadian Organ Replacement Register, the Cox proportional hazards (PH) model was employed to study survival outcomes for patients initiating PD as compared to HD in Canada from 1991 to 2004 with follow-up to 31 December 2007. Comparisons of outcomes were made between three successive calendar periods: 1991-95, 1996-2000 and 2001-04 with the relative risk of death of incident patients calculated using an intent-to-treat (ITT) analysis with proportional and non-PH models using a piecewise exponential survival model to compare adjusted mortality rates. In the ITT analysis, overall survival for the entire study period favored PD in the first 18 months and HD after 36 months. However, for the 2001-04 cohort, survival favored PD for the first 2 years and thereafter PD and HD were similar. Among female patients > 65 years with diabetes, PD had a 27% higher mortality rate. Overall, HD and PD are associated with similar outcomes for end-stage renal disease treatment in Canada.

Do Parkinson's disease patients disclose their adverse events spontaneously?

PubMed

Perez-Lloret, Santiago; Rey, María Verónica; Fabre, Nelly; Ory, Fabienne; Spampinato, Umberto; Montastruc, Jean-Louis; Rascol, Olivier

2012-05-01

Underreporting of adverse drug reactions is common but has been rarely studied in Parkinson's disease (PD). To compare the prevalence of adverse events (AEs) in relation to antiparkinsonian drugs in PD patients using two different data collection methods: patient's spontaneous reporting versus a predefined investigator-driven structured interview. Secondary objectives were to assess factors related to spontaneous reporting and to compare the rate of AE reporting in PD patients with that of a group of non-parkinsonian post-stroke patients. Cross-sectional study. Ambulatory, cognitively intact PD or post-stroke outpatients. None. Patients were first asked by means of an an open question to disclose any unpleasant effects in connection with their current medications that had occurred during the previous week. Afterwards, a predefined questionnaire listing the most common AEs known to be related to antiparkinsonian drugs was used to question the same patients in a systematic manner about the presence of any AE during the same week. Chronological and semiological criteria were used to classify the reported AEs as "unrelated" or "possibly/plausibly related" to the antiparkinsonian treatment. A total of 203 PD and 52 post-stroke patients of comparable age and sex were recruited. Eighty-five PD and five post-stroke patients reported spontaneously at least one AE (42 vs. 10%, p < 0.01), while 203 PD and 47 post-stroke patients reported at least one AE following the structured questionnaire (100 vs. 90%, p < 0.001). In PD patients, there were a total of 112 spontaneously reported AEs as compared with 1,574 according to the structured questionnaire (7%). Spontaneous disclosure of AEs was associated with experiencing >2 AEs [OR = 1.2 (1.1-3.2)], logistic regression). Seventy-four percent of PD patients had ≥1 AE possibly/plausibly related to antiparkinsonian drugs. Results showed that only 7% of AEs were reported spontaneously by patients, thus underscoring the importance of systematically asking about AEs in PD patients.

Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

PubMed

Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

2013-01-01

Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.

Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

PubMed Central

Bolitho, Samuel J.; Naismith, Sharon L.; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R.; Lewis, Simon J. G.

2013-01-01

Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms. PMID:24278399

Assessment of postural asymmetry in mild to moderate Parkinson's disease.

PubMed

Geurts, A C H; Boonstra, T A; Voermans, N C; Diender, M G; Weerdesteyn, V; Bloem, B R

2011-01-01

Asymmetry of symptoms of Parkinson's disease is clinically most evident for appendicular impairments. For axial impairments such as freezing of gait, asymmetry is less obvious. To date, asymmetries in balance control in PD patients have seldom been studied. Therefore, in this study we investigated whether postural control can be asymmetrically affected in mild to moderate PD patients. Seventeen PD patients were instructed to stand as still and symmetrically as possible on a dual force-plate during two trials. Dynamic postural asymmetry was assessed by comparing the centre-of-pressure velocities between both legs. Results showed that four patients (24%) had dynamic postural asymmetry, even after correcting for weight-bearing asymmetry. Hence, this study suggests that postural control can be asymmetrical in early PD. However, future studies should investigate the prevalence of dynamic postural asymmetry, in a larger group of PD patients. It should also be further investigated whether this approach can be used as a tool to support the initial diagnosis or monitor disease progression, or as an outcome measure for interventions aimed at improving balance in PD. Copyright © 2010 Elsevier B.V. All rights reserved.

The sensitivity of the sole of the foot in patients with Morbus Parkinson.

PubMed

Prätorius, B; Kimmeskamp, S; Milani, T L

2003-08-07

The sensory input of the foot has an important influence on balance. In patients with Morbus Parkinson (PD-patients) balance control is often impaired. Therefore, the aim of this study was to quantify the sensitivity of the plantar foot in PD-patients. Five sites of the plantar foot were examined in 24 PD-patients and in 20 controls using Semmes-Weinstein Monofilaments for touch pressure and a vibration-exciter (30 Hz) for vibration. The results show significantly higher thresholds in PD-patients. For each tested location (except the heel) the thresholds are at least twice as high as in controls. Moreover, this study proved the correlation between motor and somatosensory systems: the stronger the motor deficiencies in PD-patients (Unified Parkinson's Disease Rating System score) the higher the sensitivity thresholds for vibration. In conclusion, reduced sensitivity of the plantar foot may contribute to impaired balance control.

Metabolomics study on primary dysmenorrhea patients during the luteal regression stage based on ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry

PubMed Central

Fang, Ling; Gu, Caiyun; Liu, Xinyu; Xie, Jiabin; Hou, Zhiguo; Tian, Meng; Yin, Jia; Li, Aizhu; Li, Yubo

2017-01-01

Primary dysmenorrhea (PD) is a common gynecological disorder which, while not life-threatening, severely affects the quality of life of women. Most patients with PD suffer ovarian hormone imbalances caused by uterine contraction, which results in dysmenorrhea. PD patients may also suffer from increases in estrogen levels caused by increased levels of prostaglandin synthesis and release during luteal regression and early menstruation. Although PD pathogenesis has been previously reported on, these studies only examined the menstrual period and neglected the importance of the luteal regression stage. Therefore, the present study used urine metabolomics to examine changes in endogenous substances and detect urine biomarkers for PD during luteal regression. Ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was used to create metabolomic profiles for 36 patients with PD and 27 healthy controls. Principal component analysis and partial least squares discriminate analysis were used to investigate the metabolic alterations associated with PD. Ten biomarkers for PD were identified, including ornithine, dihydrocortisol, histidine, citrulline, sphinganine, phytosphingosine, progesterone, 17-hydroxyprogesterone, androstenedione, and 15-keto-prostaglandin F2α. The specificity and sensitivity of these biomarkers was assessed based on the area under the curve of receiver operator characteristic curves, which can be used to distinguish patients with PD from healthy controls. These results provide novel targets for the treatment of PD. PMID:28098892

Personality disorder moderates outcome in short- and long-term group analytic psychotherapy: A randomized clinical trial.

PubMed

Lorentzen, Steinar; Ruud, Torleif; Fjeldstad, Anette; Høglend, Per A

2015-06-01

In a randomized clinical trial, short- and long-term psychodynamic group psychotherapy (STG and LTG, respectively) schedules were equally effective for the 'typical' patient during a 3-year study period. Although several studies have reported good effects for patients with personality disorders (PD) in diverse forms of psychotherapy, the significance of treatment duration is unclear. Therefore, we tested the hypothesis that PD patients would improve more during and after LTG than STG. A randomized, longitudinal, prospective study contrasting the outcomes during and after short- and long-term dynamic group psychotherapies. One hundred and sixty-seven outpatients with mood disorders, anxiety disorders, or PD were randomized to STG or LTG (respectively, 20 or 80 weekly sessions of 90 min each). Outcome measures are as follows: symptoms (SCL-90-R), interpersonal problems (IIP-C), and psychosocial functioning (GAF split version: GAF-Symptom and GAF-Function). PD pathology (number of PD criteria items) was selected a priori as a putative moderator of treatment effects. Change during the 3-year study period was assessed using linear mixed models. The study was registered at ClinicalTrials.gov as NCT 00021417. Our hypothesis was supported, as patients with PD improved significantly more regarding all outcome variables in LTG than STG. For patients without PD, the rate of change was similar across 3 years; however, the rate of change in symptoms and interpersonal problems was higher in STG during the first 6 months. The effectiveness of LTG is higher for patients with co-morbid PD. Patients without PD do not appear to experience additional gain from LTG. Clinical implications: LTG demonstrates better effectiveness than STG for patients with personality disorder co-morbidity (PD). Patients without PD do not appear to experience additional gain from attending LTG. Correct initial allocation to treatment duration may prevent disruptive breaks in relationships and lead to both human and economic cost savings. Limitations: Trials on mixed diagnostic samples may limit the ability to fully assess change for specific diagnostic groups. Therapists were unable to select patients and compose their own groups. Although this condition might increase the generalizability of the results, it may also have restricted the therapists and the clinical situation inadvertently. © 2014 The British Psychological Society.

Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials.

PubMed

O'Connor, Jeremy M; Fessele, Kristen L; Steiner, Jean; Seidl-Rathkopf, Kathi; Carson, Kenneth R; Nussbaum, Nathan C; Yin, Emily S; Adelson, Kerin B; Presley, Carolyn J; Chiang, Anne C; Ross, Joseph S; Abernethy, Amy P; Gross, Cary P

2018-05-10

The US Food and Drug Administration (FDA) is increasing its pace of approvals for novel cancer therapeutics, including for immune checkpoint inhibitors of programmed cell death 1 protein (anti-PD-1 agents). However, little is known about how quickly anti-PD-1 agents reach eligible patients in practice or whether such patients differ from those studied in clinical trials that lead to FDA approval (pivotal clinical trials). To assess the speed with which anti-PD-1 agents reached eligible patients in practice and to compare the ages of patients treated in clinical practice with the ages of those treated in pivotal clinical trials. This retrospective cohort study, performed from January 1, 2011, through August 31, 2016, included patients from the Flatiron Health Network who were eligible for anti-PD-1 treatment of selected cancer types, which included melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). Cumulative proportions of eligible patients receiving anti-PD-1 treatment and their age distributions. The study identified 3089 patients who were eligible for anti-PD-1 treatment (median age, 66 [interquartile range, 56-75] years for patients with melanoma, 66 [interquartile range, 58-72] years for patients with RCC, and 67 [interquartile range, 59-74] years for patients with NSCLC; 1742 male [56.4%] and 1347 [43.6%] female; 2066 [66.9%] white). Of these patients, 2123 (68.7%) received anti-PD-1 treatment, including 439 eligible patients with melanoma (79.1%), 1417 eligible patients with NSCLC (65.6%), and 267 eligible patients with RCC (71.2%). Within 4 months after FDA approval, greater than 60% of eligible patients in each cohort had received anti-PD-1 treatment. Overall, similar proportions of older and younger patients received anti-PD-1 treatment during the first 9 months after FDA approval. However, there were significant differences in age between clinical trial participants and patients receiving anti-PD-1 treatment in clinical practice, with more patients being older than 65 years in clinical practice (range, 327 of 1365 [60.6%] to 46 of 72 [63.9%]) than in pivotal clinical trials (range, 38 of 120 [31.7%] to 223 of 544 [41.0%]; all P < .001). Anti-PD-1 agents rapidly reached patients in clinical practice, and patients treated in clinical practice differed significantly from patients treated in pivotal clinical trials. Future actions are needed to ensure that rapid adoption occurs on the basis of representative trial evidence.

Tremor pattern differentiates drug-induced resting tremor from Parkinson disease.

PubMed

Nisticò, R; Fratto, A; Vescio, B; Arabia, G; Sciacca, G; Morelli, M; Labate, A; Salsone, M; Novellino, F; Nicoletti, A; Petralia, A; Gambardella, A; Zappia, M; Quattrone, A

2016-04-01

DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD. This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. Rest tremor amplitude was higher in PD patients than in rDIP patients (p < 0.001), while frequency and burst duration were higher in rDIP than in PD (p < 0.001, p < 0.003, respectively). Resting tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p < 0.001). DAT-SPECT was normal in rDIP patients while it was markedly abnormal in patients with PD. In the absence of DAT-SPECT, the pattern of resting tremor can be considered a useful investigation for differentiating rDIP from PD. Copyright © 2016. Published by Elsevier Ltd.

Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients

PubMed Central

Politis, Marios; Wu, Kit; Loane, Clare; Brooks, David J.; Kiferle, Lorenzo; Turkheimer, Federico E.; Bain, Peter; Molloy, Sophie; Piccini, Paola

2014-01-01

Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson’s disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD. PMID:24531549

Quality of Life and Physical Function in Older Patients on Dialysis: A Comparison of Assisted Peritoneal Dialysis with Hemodialysis

PubMed Central

Iyasere, Osasuyi U.; Johansson, Lina; Huson, Les; Smee, Joanna; Maxwell, Alexander P.; Farrington, Ken; Davenport, Andrew

2016-01-01

Background and objectives In-center hemodialysis (HD) is often the default dialysis modality for older patients. Few centers use assisted peritoneal dialysis (PD), which enables treatment at home. This observational study compared quality of life (QoL) and physical function between older patients on assisted PD and HD. Design, setting, participants, & measurements Patients on assisted PD who were >60 years old and on dialysis for >3 months were recruited and matched to patients on HD (needing hospital transport) by age, sex, diabetes, dialysis vintage, ethnicity, and index of deprivation. Frailty was assessed using the Clinical Frailty Scale. QoL assessments included Hospital Anxiety and Depression Scale (HADS), Short Form-12, Palliative Outcomes Symptom Scale (renal), Illness Intrusiveness Rating Scale, and Renal Treatment Satisfaction Questionnaire (RTSQ). Physical function was evaluated by Barthel Score and timed up and go test. Results In total, 251 patients (129 PD and 122 HD) were recruited. In unadjusted analysis, patients on assisted PD had a higher prevalence of possible depression (HADS>8; PD=38.8%; HD=23.8%; P=0.05) and higher HADS depression score (median: PD=6; HD=5; P=0.05) but higher RTSQ scores (median: PD=55; HD=51; P<0.01). In a generalized linear regression model adjusting for age, sex, comorbidity, dialysis vintage, and frailty, assisted PD continued to be associated with higher RTSQ scores (P=0.04) but not with other QoL measures. Conclusions There are no differences in measures of QoL and physical function between older patients on assisted PD and comparable patients on HD, except for treatment satisfaction, which is higher in patients on PD. Assisted PD should be considered as an alternative to HD for older patients, allowing them to make their preferred choices. PMID:26712808

To rise and to fall: functional connectivity in cognitively normal and cognitively impaired patients with Parkinson's disease.

PubMed

Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan

2015-04-01

Cognitive decline is a burdensome extra-motor symptom associated with Parkinson's disease (PD). This study aimed at investigating intrinsic functional connectivity (iFC) of the brain in cognitively unimpaired (PD-CU) and impaired PD patients (PD-CI) compared with age-matched healthy controls. "Resting-state" functional magnetic resonance imaging was acquired in 53 subjects, that is, 14 PD-CU patients, 17 PD-CI patients, and 22 control subjects. Cognition and cognitive status for patient classification were assessed using detailed neuropsychological testing. In PD-CU patients versus controls, we demonstrated significantly increased iFC (hyperconnectivity) presenting as network expansions in cortical, limbic, and basal ganglia-thalamic areas. Significantly, decreased iFC in PD-CI patients compared with control subjects was observed, predominantly between major nodes of the default mode network. In conclusion, the increased iFC might be the initial manifestation of altered brain function preceding cognitive deficits. Hyperconnectivity could be an adaptive (compensatory) mechanism by recruiting additional resources to maintain normal cognitive performance. As PD-related pathology progresses, functional disruptions within the default mode networks seem to be considerably associated with cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression of PD-1 on peripheral blood Treg cells is related to the diagnosis, prognosis and treatment of T cell non-Hodgkin lymphoma.

PubMed

Zuo, Mengxuan; Shen, Haorui; Yin, Jingjing; Wang, Wei; Zhang, Yan; Zhou, Dao-Bin; Zhang, Wei

2018-05-24

The aim of study was to explore the PD-1 expression on Treg cells and its association with T-NHL. 137 patients newly diagnosed with T-NHL and 115 healthy controls were enrolled. The expression level of PD-1 was measured by flow cytometry at the time of diagnose and 3-8 course of treatment. Median fluorescence intensity (MFI) of PD-1 on Treg cells in T-NHL patients was significantly higher than that in healthy controls (P < 0.001). MFI of PD-1 in medium/high-risk T-NHL patients were higher than that in low-risk patients (P < 0.05). After treatment with Chidamide combined with chemotherapy, MFI of PD-1 significantly decreased (P < 0.05). In patients with high PD-1 expression (percentage>19.6% and MFI > 580), EFS was significantly lower than patients with low PD-1 expression (percentage<19.6% and MFI < 580). The PD-1expression on peripheral blood Treg cells of T-NHL patients is related to the diagnosis, prognosis and treatment of disease. Copyright © 2018. Published by Elsevier Ltd.

Iowa Gambling Task Performance in Parkinson Disease Patients with Impulse Control Disorders.

PubMed

Biars, Julia W; Johnson, Nicole L; Nespeca, Michelle; Busch, Robyn M; Kubu, Cynthia S; Floden, Darlene P

2018-04-27

A subgroup of patients with Parkinson disease (PD) develops impulse control disorders (ICD) associated with their dopamine replacement therapy. Patients and their families may be reluctant to report ICD symptoms or unaware these symptoms are related to PD medication, which can make detecting an ICD difficult for clinicians. Ideally, a behavioral measure that is sensitive to ICD could be employed to ensure that patients with these behaviors are identified and treated. The Iowa Gambling Task (IGT), a standardized decision-making task, has proven sensitive in other populations with impulse control problems. We hypothesized that the IGT would differentiate between PD patients with and without ICD. We compared IGT performance and disease variables in 24 PD patients with ICD and 24 PD patients without ICD. Patient groups were matched in terms of age, sex, and duration of PD. There were no significant differences in IGT scores between PD groups. IGT performance declined with increasing age, but the majority of patients performed within normal limits based on published age- and education-corrected normative data. The IGT did not distinguish between PD patients with and without ICD. Increasing age negatively impacted performance in both groups. Other studies have found that IGT performance may decline in normal aging. Our results suggest that the IGT lacks the sensitivity and specificity needed to differentiate between age-related deficits and disruption in frontal-subcortical circuits underlying ICD associated with PD medications. Therefore, the IGT is not an appropriate behavioral measure for ICD in PD patients.

White matter correlates of anxiety sensitivity in panic disorder.

PubMed

Kim, Min-Kyoung; Kim, Borah; Kiu Choi, Tai; Lee, Sang-Hyuk

2017-01-01

Anxiety sensitivity (AS) refers to a fear of anxiety-related sensations and is a dispositional variable especially elevated in patients with panic disorder (PD). Although several functional imaging studies of AS in patients with PD have suggested the presence of altered neural activity in paralimbic areas such as the insula, no study has investigated white matter (WM) alterations in patients with PD in relation to AS. The objective of this study was to investigate the WM correlates of AS in patients with PD. One-hundred and twelve right-handed patients with PD and 48 healthy control (HC) subjects were enrolled in this study. The Anxiety Sensitivity Inventory-Revised (ASI-R), the Panic Disorder Severity Scale (PDSS), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were administered. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis. Among the patients with PD, the ASI-R total scores were significantly correlated with the fractional anisotropy values of the WM regions near the insula, the splenium of the corpus callosum, the tapetum, the fornix/stria terminalis, the posterior limb of the internal capsule, the retrolenticular part of the internal capsule, the posterior thalamic radiation, the sagittal striatum, and the posterior corona radiata located in temporo-parieto-limbic regions and are involved in interoceptive processing (p<0.01; threshold-free cluster enhancement [TFCE]-corrected). These WM regions were also significantly correlated with the APPQ interoceptive avoidance subscale and BDI scores in patients with PD (p<0.01, TFCE-corrected). Correlation analysis among the HC subjects revealed no significant findings. There has been no comparative study on the structural neural correlates of AS in PD. The current study suggests that the WM correlates of AS in patients with PD may be associated with the insula and the adjacent temporo-parieto-limbic WM regions, which may play important roles in interoceptive processing in the brain and in depression in PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Alterations in regional homogeneity of resting-state brain activity in fatigue of Parkinson's disease.

PubMed

Li, Junyi; Yuan, Yongsheng; Wang, Min; Zhang, Jiejin; Zhang, Li; Jiang, Siming; Ding, Jian; Zhang, Kezhong

2017-10-01

Fatigue is a common complaint in patients with Parkinson's disease (PD). However, the neural bases of fatigue in PD remain uncertain. In this cross-sectional study, our aim was to study the change of the local brain function in PD patients with fatigue. Among 49 patients with PD, 17 of them had fatigue and the remaining 32 patients without fatigue, and 25 age- and gender-matched healthy controls were enrolled. All subjects were evaluated with Fatigue Severity Scale (FSS) and had a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The fMRI images were analyzed using regional homogeneity (ReHo) to study the change of the local brain function. ReHo analysis controlling for gray matter volume, age, gender, and education showed decreased ReHo in the left anterior cingulate cortex (ACC) and the right superior frontal gyrus (dorsolateral part), and increased ReHo in the left postcentral gyrus and the right inferior frontal gyrus (orbital and triangular part), compared PD-F with PD-NF; In PD patients, the regional activity in the left ACC and the right superior frontal gyrus (dorsolateral part) was negatively correlated with the FSS scores, while that in the left postcentral gyrus, the right inferior frontal gyrus (orbital and triangular part) was positively correlated with the FSS scores. This study demonstrates that brain areas including frontal, postcentral and ACC regions indicative of sensory, motor, and cognitive systems are involved in fatigue in PD patients.

White matter microstructure damage in tremor-dominant Parkinson's disease patients.

PubMed

Luo, ChunYan; Song, Wei; Chen, Qin; Yang, Jing; Gong, QiYong; Shang, Hui-Fang

2017-07-01

Resting tremor is one of the cardinal motor features of Parkinson's disease (PD). Several lines of evidence suggest resting tremor may have different underlying pathophysiological processes from those of bradykinesia and rigidity. The current study aims to identify white matter microstructural abnormalities associated with resting tremor in PD. We recruited 60 patients with PD (30 with tremor-dominant PD and 30 with nontremor-dominant PD) and 26 normal controls. All participants underwent clinical assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate white matter integrity across the entire white matter tract skeleton. Compared with both healthy controls and the nontremor-dominant PD patients, the tremor-dominant PD patients were characterized by increased mean diffusivity (MD) and axial diffusivity (AD) along multiple white matter tracts, mainly involving the cerebello-thalamo-cortical (CTC) pathway. The mean AD value in clusters with significant difference was correlated with resting tremor score in the tremor-dominant PD patients. There was no significant difference between the nontremor-dominant PD patients and controls. Our results support the notion that resting tremor in PD is a distinct condition in which significant microstructural white matter changes exist and provide evidence for the involvement of the CTC in tremor genesis of PD.

Risk for femoral fractures in Parkinson's disease patients with and without severe functional impairment.

PubMed

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Impaired balance is a major problem in patients with idiopathic Parkinson's disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28-2.98) than in women (HR = 1.79; 95%-CI: 1.66-1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment.

Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1.

PubMed

Champiat, Stéphane; Dercle, Laurent; Ammari, Samy; Massard, Christophe; Hollebecque, Antoine; Postel-Vinay, Sophie; Chaput, Nathalie; Eggermont, Alexander; Marabelle, Aurélien; Soria, Jean-Charles; Ferté, Charles

2017-04-15

Purpose: While immune checkpoint inhibitors are disrupting the management of patients with cancer, anecdotal occurrences of rapid progression (i.e., hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs. The prevalence, the natural history, and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown. Experimental Design: Medical records from all patients ( N = 218) prospectively treated in Gustave Roussy by anti-PD-1/PD-L1 within phase I clinical trials were analyzed. The tumor growth rate (TGR) prior ("REFERENCE"; REF) and upon ("EXPERIMENTAL"; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR, clinicopathologic characteristics, and overall survival (OS) were computed. Results: HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 131 evaluable patients, 12 patients (9%) were considered as having HPD. HPD was not associated with higher tumor burden at baseline, nor with any specific tumor type. At progression, patients with HPD had a lower rate of new lesions than patients with disease progression without HPD ( P < 0.05). HPD is associated with a higher age ( P < 0.05) and a worse outcome (overall survival). Interestingly, REF TGR (before treatment) was inversely correlated with response to anti-PD-1/PD-L1 ( P < 0.05) therapy. Conclusions: A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1. This observation raises some concerns about treating elderly patients (>65 years old) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon. Clin Cancer Res; 23(8); 1920-8. ©2016 AACR See related commentary by Sharon, p. 1879 . ©2016 American Association for Cancer Research.

Peritoneal dialysis for older people: overcoming the barriers.

PubMed

Brown, E A

2008-04-01

The proportion of older dialysis patients on peritoneal dialysis (PD) is considerably lower than that of younger patients. This is despite the fact that clinical outcome studies show that older patients cope at least as well as younger patients with PD, and that many older patients do not cope well with hemodialysis (HD). Barriers to PD include medical and social factors, physician bias, late referral, and education not tailored to the needs of older patients. The development of assisted PD can overcome some of the barriers and enable frail older patients to have home-based dialysis treatment.

PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients.

PubMed

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Dietrich, Dimo

2017-01-01

This study evaluates promoter methylation of the programmed cell death ligand 1 (PD-L1) as a biomarker in a cohort of 383 colorectal cancer patients. PD-L1 methylation (m PD-L1 ) was inversely correlated with PD-L1 mRNA expression ( p = 0.001) and was associated with significantly shorter overall survival (OS, p = 0.003) and recurrence-free survival (RFS, p < 0.001). In age-stratified multivariate Cox proportional hazards analyses including sex, tumor, nodal, distant metastasis categories, microsatellite instability (MSI)-status, and PD-L1 mRNA, m PD-L1 is classified as an independent prognostic factor (OS: p = 0.030; RFS: p < 0.001). Further studies are needed to evaluate PD-L1 methylation as a biomarker for response prediction of immunotherapies targeting the PD-1/PD-L1 axis.

Speech rate in Parkinson's disease: A controlled study.

PubMed

Martínez-Sánchez, F; Meilán, J J G; Carro, J; Gómez Íñiguez, C; Millian-Morell, L; Pujante Valverde, I M; López-Alburquerque, T; López, D E

2016-09-01

Speech disturbances will affect most patients with Parkinson's disease (PD) over the course of the disease. The origin and severity of these symptoms are of clinical and diagnostic interest. To evaluate the clinical pattern of speech impairment in PD patients and identify significant differences in speech rate and articulation compared to control subjects. Speech rate and articulation in a reading task were measured using an automatic analytical method. A total of 39 PD patients in the 'on' state and 45 age-and sex-matched asymptomatic controls participated in the study. None of the patients experienced dyskinesias or motor fluctuations during the test. The patients with PD displayed a significant reduction in speech and articulation rates; there were no significant correlations between the studied speech parameters and patient characteristics such as L-dopa dose, duration of the disorder, age, and UPDRS III scores and Hoehn & Yahr scales. Patients with PD show a characteristic pattern of declining speech rate. These results suggest that in PD, disfluencies are the result of the movement disorder affecting the physiology of speech production systems. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Factors Associated with the Choice of Peritoneal Dialysis in Patients with End-Stage Renal Disease.

PubMed

Chiang, Pei-Chun; Hou, Jia-Jeng; Jong, Ing-Ching; Hung, Peir-Haur; Hsiao, Chih-Yen; Ma, Tsung-Liang; Hsu, Yueh-Han

2016-01-01

The purpose of this study was to analyze the factors associated with receiving peritoneal dialysis (PD) in patients with incident end-stage renal disease (ESRD) in a hospital in Southern Taiwan. The study included all consecutive patients with incident ESRD who participated in a multidisciplinary predialysis education (MPE) program and started their first dialysis therapy between January 1, 2008, and June 30, 2013, in the study hospital. We provided small group teaching sessions to advanced CKD patients and their family to enhance understanding of various dialysis modalities. Multivariate logistic regression models were used to analyze the association of patient characteristics with the chosen dialysis modality. Of the 656 patients, 524 (80%) chose hemodialysis and 132 chose PD. Our data showed that young age, high education level, and high scores of activities of daily living (ADLs) were positively associated with PD treatment. Patients who received small group teaching sessions had higher percentages of PD treatment (30.5% versus 19.5%; P = 0.108) and preparedness for dialysis (61.1% versus 46.6%; P = 0.090). Young age, high education level, and high ADL score were positively associated with choosing PD. Early creation of vascular access may be a barrier for PD.

Effects of task structure on category priming in patients with Parkinson's disease and in healthy individuals.

PubMed

Brown, Gregory G; Brown, Sandra J; Christenson, Gina; Williams, Rebecca E; Kindermann, Sandra S; Loftis, Christopher; Olsen, Ryan; Siple, Patricia; Shults, Clifford; Gorell, Jay M

2002-05-01

Lexical decision tasks have been used to study both shifts of attention and semantic processing in Parkinson's Disease (PD). Whereas other laboratories have reported normal levels of semantic priming among PD patients, our laboratory has reported abnormally large levels. In this study, two experiments were performed to determine the influence of task structure on the extent of semantic priming during lexical decision-making and pronunciation tasks among PD patients and neurologically healthy controls. In Experiment 1, the effect of Prime Dominance (the ratio of category to neutral trials) on lexical decision-making was studied. Although equal numbers of word and nonword trials were presented, half of the PD patients and controls were studied under Category Prime Dominance (category : neutral prime ratio of 2:1) and half were studied under Neutral Prime Dominance (category : neutral prime ratio of 1:2). In Experiment 2, PD and control participants were studied on lexical decision-making and pronunciation tasks where twice as many words as nonword trials were presented, consistent with other studies from our laboratory. In Experiment 1, we found no group differences in the magnitude of priming and no effect of Prime Dominance. Moreover, the findings were similar in pattern and magnitude to results published by Neely (1977). In Experiment 2, we observed larger priming effects among PD patients than among controls, but only on the lexical decision (LD) task. These results support the hypothesis that abnormally large category-priming effects appear in LD studies of PD patients when the number of word trials exceeds the number of nonword trials. Furthermore, increased lexical priming in PD appears to be due to processes operating during the decision-making period that follows presentation of the lexical target.

Predictive model for falling in Parkinson disease patients.

PubMed

Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Montesinos, Rosa; Castro-Suarez, Sheila; Cuenca-Alfaro, Jose; Cortijo, Patricia

2016-12-01

Falls are a common complication of advancing Parkinson's disease (PD). Although numerous risk factors are known, reliable predictors of future falls are still lacking. The aim of this study was to develop a multivariate model to predict falling in PD patients. Prospective cohort with forty-nine PD patients. The area under the receiver-operating characteristic curve (AUC) was calculated to evaluate predictive performance of the purposed multivariate model. The median of PD duration and UPDRS-III score in the cohort was 6 years and 24 points, respectively. Falls occurred in 18 PD patients (30%). Predictive factors for falling identified by univariate analysis were age, PD duration, physical activity, and scores of UPDRS motor, FOG, ACE, IFS, PFAQ and GDS ( p -value < 0.001), as well as fear of falling score ( p -value = 0.04). The final multivariate model (PD duration, FOG, ACE, and physical activity) showed an AUC = 0.9282 (correctly classified = 89.83%; sensitivity = 92.68%; specificity = 83.33%). This study showed that our multivariate model have a high performance to predict falling in a sample of PD patients.

33 Years of Peritoneal Dialysis-Associated Peritonitis: A Single-Center Study in Japan.

PubMed

Nakao, Masatsugu; Yamamoto, Izumi; Maruyama, Yukio; Nakashima, Akio; Matsuo, Nanae; Tanno, Yudo; Ohkido, Ichiro; Ikeda, Masato; Yamamoto, Hiroyasu; Yokoyama, Keitaro; Yokoo, Takashi

2016-02-01

Peritoneal dialysis-associated peritonitis (PD-associated peritonitis) could influence the outcome of PD patients, including technique survival. Although the use of the twin-bag system has decreased the incidence of peritonitis, the effects of biocompatible PD solutions are controversial. Additionally, since both infection-causing microorganisms and antimicrobial therapies have changed over time, the duration of treatment of peritonitis (the duration of peritonitis) seems to have changed. The study included 527 patients who received PD between January 1980 and December 2012 at a single center. We divided patients undergoing PD into three groups according to the type of PD system used, namely single-bag and conventional PD solutions (S+C group, N = 145), twin-bag and conventional PD solutions (T+C group, N = 171) and twin-bag and biocompatible PD solutions (T+B group, N = 211), and analyzed PD-associated peritonitis incidences. Incidences of PD-associated peritonitis (times per patient-months) and peritonitis-free time were 1/59.4, 1/70.6 and 1/103.1, and 52, 97, and 100 months for the S+C, T+C and T+B groups, respectively. The duration of peritonitis, has thus, become dramatically shorter in recent years. Streptococcus sp. were associated with shortest and fungi with longest durations of peritonitis. Staphylococcus sp. and Pseudomonas aeruginosa were predominant in the S+C group. The twin-bag system has made a greater contribution to reductions in PD-associated peritonitis than biocompatible PD solutions. Furthermore, changes in microorganisms, antimicrobial therapies, patient education and improved PD system devices have presumably affected the reduction in the duration of peritonitis. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Plasma antioxidant status and motor features in de novo Chinese Parkinson's disease patients.

PubMed

Yuan, Yongsheng; Tong, Qing; Zhang, Li; Jiang, Siming; Zhou, Hong; Zhang, Rui; Zhang, Shu; Xu, Qinrong; Li, Daqian; Zhou, Xiaobin; Ding, Jian; Zhang, Kezhong

2016-01-01

This study aimed to explore plasma antioxidant status in de novo Chinese Parkinson's disease (PD) patients and investigate its relationship with specific motor features of PD. Sixty-four de novo Chinese PD patients and 40 age- and sex-matched healthy controls were recruited. Each motor feature of PD patients was assessed by unified Parkinson's disease rating scale. Plasma antioxidant status, including plasma level of glutathione (GSH) and plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), was detected using enzyme-linked immunosorbent assay. The relationship between the plasma antioxidant status and motor features of PD was evaluated by Spearman's coefficient. Plasma GSH level and plasma activities of GSH-Px, CAT and SOD of PD patients were lower than those of healthy controls. Moreover, the declining activity of plasma CAT was related with the increasing mean postural instability and gait disorder (PIGD) score and growing age. In contrast, the severity of tremor was positively correlated with plasma SOD activity. Our study demonstrates that the plasma antioxidant status is impaired in de novo Chinese PD patients. The complex relationship between the plasma antioxidant status and different motor features indicates that the antioxidant mechanisms underlying tremor and PIGD of PD may be different.

Periocular dermatitis: a report of 401 patients.

PubMed

Temesvári, E; Pónyai, G; Németh, I; Hidvégi, B; Sas, A; Kárpáti, S

2009-02-01

Periocular contact dermatitis may appear as contact conjunctivitis, contact allergic and/or irritative eyelid and periorbital dermatitis, or a combination of these symptoms. The clinical symptoms may be induced by several environmental and therapeutic contact allergens. The aim of the present study was to map the eliciting contact allergens in 401 patients with periocular dermatitis (PD) by patch testing with environmental and ophthalmic contact allergens. Following the methodics of international requirements, 401 patients were tested with contact allergens of the standard environmental series, 133 of 401 patients with the Brial ophthalmic basic and supplementary series as well. Contact hypersensitivity was detected in 34.4% of the patients. Highest prevalence was seen in cases of PD without other symptoms (51.18%), in patients of PD associated with ophthalmic complaints (OC; 30.4%), and PD associated with atopic dermatitis (AD; 27.9%). In the subgroup of PD associated with seborrhoea (S) and rosacea (R), contact hypersensitivity was confirmed in 17.6%. Most frequent sensitisers were nickel sulphate (in 8.9% of the tested 401 patients), fragrance mix I (4.5%), balsam of Peru (4.0%), paraphenylendiamine (PPD) (3.7%), and thiomersal (3.5%). By testing ophthalmic allergens, contact hypersensitivity was observed in nine patients (6.7% of the tested 133 patients). The most common confirmed ophthalmic allergens were cocamidopropyl betaine, idoxuridine, phenylephrine hydrochloride, Na chromoglycinate, and papaine. Patients with symptoms of PD were tested from 1996 to 2006. The occurence of contact hypersensitivity in PD patients was in present study 34.4%. A relatively high occurrence was seen in cases of PD without other symptoms, in PD + OC and in PD + AD patients. The predominance of environmental contact allergens was remarkable: most frequent sensitizers were nickel sulphate, fragrance mix I, balsam of Peru, thiomersal, and PPD. The prevalence of contact hypersensitivity to ophthalmic allergens did not exceed l.5%.

Hydration and nutritional status in patients on home-dialysis-A single centre study.

PubMed

Li, Janet S C; Chan, John Y H; Tai, Mandy M Y; Wong, So M; Pang, S M; Lam, Fanny Y F; Chu, Carmen H M; Ching, Chris S Y; Wong, Joseph H S; Chak, W L

2018-04-17

Over-hydration (OH) and malnutrition are prevalent among patients on dialysis therapy. The prevalence of OH and malnutrition as well as the risk factors associated with OH and malnutrition in our patients on home peritoneal dialysis (PD) and home haemodialysis (HD) are examined. This was a cross-sectional study. The hydration and nutritional status of the study groups were assessed by a Body Composition Monitor. Patients who were stable on home dialysis therapy for over one year were invited to participate. Univariate and multivariate analyses were performed to identify associated factors and determine the predictors of OH and malnutrition, respectively. Eighty-eight patients (41 PD and 47 home HD) were recruited. A 32.95% of our patients on home dialysis therapy were in OH status. There was a significance difference in the prevalence of hydration status between patients on PD and home HD (p = 0.014), as overhydration was more common in patients on PD than home HD (46.34 vs. 21.28%). Dehydration was more common in patients on home HD than PD (29.79 vs. 9.76%). Male gender, decreasing haemoglobin level and presence of diabetes mellitus (DM) were risk factors of OH on multivariable analysis. There was no significance difference in the prevalence of malnutrition between patients on PD and home HD (p = 0.27). Increasing Fat Tissue Index (FTI), height and patients on PD therapy were at higher risk of malnutrition. OH and malnutrition were prevalent patients on home dialysis therapy. © 2018 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Comparison of frequency, risk factors, and time course of postoperative delirium in octogenarians after transcatheter aortic valve implantation versus surgical aortic valve replacement.

PubMed

Eide, Leslie S P; Ranhoff, Anette H; Fridlund, Bengt; Haaverstad, Rune; Hufthammer, Karl Ove; Kuiper, Karel K J; Nordrehaug, Jan Erik; Norekvål, Tone M

2015-03-15

Postoperative delirium (PD) after transcatheter aortic valve implantation (TAVI) remains to be explored. We sought to (1) determine the incidence of PD in octogenarians who underwent TAVI or surgical aortic valve replacement (SAVR), (2) identify its risk factors, and (3) describe possible differences in the onset and course of PD between treatment groups. A prospective cohort study of consecutive patients aged ≥80 years with severe aortic stenosis who underwent elective TAVI or SAVR (N = 143) was conducted. The incidence of PD was assessed for 5 days using the Confusion Assessment Method (CAM). Risk factors for PD were studied with logistic regression. Patients treated with TAVI were older (p ≤0.001), had lower cognitive scores (p = 0.007), and more co-morbidities (p = 0.003). Despite this, significantly fewer (p = 0.013) patients treated with TAVI (44%) experienced PD compared to patients treated with SAVR (66%). Undergoing SAVR (p = 0.02) and having lower cognitive function (p = 0.03) emerged as risk factors for PD, whereas gender, activities of daily living, frailty, atrial fibrillation, and postoperative use of opioids and anxiolytics did not. Patients treated with TAVI and without PD during the first 2 postoperative days were unlikely to experience PD on subsequent days. The onset of PD after SAVR could occur at any time during the postoperative evaluation. In conclusion, SAVR in octogenarian patients with aortic stenosis might be considered as a predisposing factor for PD. Our data also suggest that the onset of PD was more unpredictable after SAVR. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Alterations of erythrocyte rheology and cellular susceptibility in end stage renal disease: Effects of peritoneal dialysis.

PubMed

Ertan, Nesrin Zeynep; Bozfakioglu, Semra; Ugurel, Elif; Sinan, Mukaddes; Yalcin, Ozlem

2017-01-01

In this study, we investigated the effects of peritoneal dialysis on hemorheological and hematological parameters and their relations with oxidant and antioxidant status of uremic patients. Hemorheological parameters (erythrocyte deformability, erythrocyte aggregation, osmotic deformability, blood and plasma viscosity) were measured in patients with renal insufficiency undergoing peritoneal dialysis (PD) and volunteers. Erythrocyte deformability, osmotic deformability and aggregation in both autologous plasma and 3% dextran 70 were measured by laser diffraction ektacytometry. Enzyme activities of glutathione peroxidase, superoxide dismutase and catalase were studied in erythrocytes; lipid peroxidation was studied by measuring the amount of malondialdehyde in both erythrocytes and plasma samples. Blood viscosity at native hematocrit was significantly lower in PD patients at all measured shear rates compared to controls, but it was high in PD patients at corrected (45%) hematocrit. Erythrocyte deformability did not show any difference between the two groups. Osmotic deformability was significantly lower in PD patients compared to controls. Aggregation index values were significantly high in PD patients in plasma Catalase and glutathione peroxidase activities in erythrocytes were decreased in PD patients whereas superoxide dismutase activity was increased compared to controls. Malondialdehyde was significantly increased in erythrocytes and plasma samples of PD patients which also shows correlations with aggregation parameters. It has been concluded that erythrocytes in PD patients are more prone to aggregation and this tendency could be influenced by lipid peroxidation activity in patient's plasma. These results imply that uremic conditions, loss of plasma proteins and an increased risk of oxidative stress because of decreasing levels of antioxidant enzymes affect erythrocyte rheology during peritoneal dialysis. This level of distortion may have crucial effects, impairing the blood flow dynamics and causing inadequate microcirculatory perfusion.

Alterations of Brain Structural Network in Parkinson's Disease With and Without Rapid Eye Movement Sleep Behavior Disorder.

PubMed

Guo, Tao; Guan, Xiaojun; Zeng, Qiaoling; Xuan, Min; Gu, Quanquan; Huang, Peiyu; Xu, Xiaojun; Zhang, Minming

2018-01-01

Rapid eye movement sleep behavior disorder (RBD) has a strong association with alpha synucleinpathies such as Parkinson's disease (PD) and PD patients with RBD tend to have a poorer prognosis. However, we still know little about the pathogenesis of RBD in PD. Therefore, we aim to detect the alterations of structural correlation network (SCN) in PD patients with and without RBD. A total of 191 PD patients, including 51 patients with possible RBD (pRBD) and 140 patients with non-possible RBD, and 76 normal controls were included in the present study. Structural brain networks were constructed by thresholding gray matter volume correlation matrices of 116 regions and analyzed using graph theoretical approaches. There was no difference in global properties among the three groups. Significant enhanced regional nodal measures in limbic system, frontal-temporal regions, and occipital regions and decreased nodal measures in cerebellum were found in PD patients with pRBD (PD-pRBD) compared with PD patients without pRBD. Besides, nodes in frontal lobe, temporal lobe, and limbic system were served as hubs in both two PD groups, and PD-pRBD exhibited additionally recruited hubs in limbic regions. Based on the SCN analysis, we found PD-pRBD exhibited a reorganization of nodal properties as well as the remapping of the hub distribution in whole brain especially in limbic system, which may shed light to the pathophysiology of PD with RBD.

Computing the variations in the self-similar properties of the various gait intervals in Parkinson disease patients.

PubMed

Manjeri Keloth, Sana; Arjunan, Sridhar P; Kumar, Dinesh

2017-07-01

This study has investigated the stride, swing, stance and double support intervals of gait for Parkinson's disease (PD) patients with different levels of severity. Self-similar properties of the gait signal were analyzed to investigate the changes in the gait pattern of the healthy and PD patients. To understand the self-similar property, detrended fluctuation analysis was performed. The analysis shows that the PD patients have less defined gait when compared to healthy. The study also shows that among the stance and swing phase of stride interval, the self-similarity is less for swing interval when compared to the stance interval of gait and decreases with the severity of gait. Also, PD patients show decreased self-similar patterns in double support interval of gait. This suggest that there are less rhythmic gait intervals and a sense of urgency to remain in support phase of gait by the PD patients.

Review of the influence of pigment dispersion and exfoliation glaucoma diagnosis on intraocular pressure in clinical trials evaluating primary open-angle glaucoma and ocular hypertension.

PubMed

Stewart, William C; DeMill, D L; Wirostko, Barbara M; Nelson, Lindsay A; Stewart, Jeanette A

2013-08-01

To evaluate published, randomized, prospective, parallel clinical trials utilizing currently approved glaucoma medications to determine what influence, if any, pigment dispersion (PD) or exfoliation glaucoma (XFG) patients had on the intraocular pressure. A review of clinical trial articles evaluating currently used topical glaucoma medicines. Articles were published between January 1995 and April 2011. If the articles met the inclusion/exclusion criteria, they were analyzed for PD and XFG. Twenty-four articles were included, containing 49 treatment arms that included PD or XFG patients. The range of PD patients was 0% to 4.5%, with a mean of 1.5±0.9%, and for XFG patients 0% to 6.3%, with a mean of 2.2±2.1%. The treatment arms with PD showed a difference in the intraocular pressures (IOPs), for all studies analyzed together, for the baseline IOPs between clinical trials that did and did not include PD patients (8 AM IOPs: with PD 26.5±0.9 mm Hg and without PD 25.8±1.3 mm Hg, P=0.024; and diurnal curve mean IOPs: with PD 25.3±1.1 mm Hg and without PD 24.5±1.3 mm Hg, P=0.024). The XFG treatment arms showed that there was a difference in the IOPs for all studies analyzed together for diurnal baseline IOPs between clinical trials that did and did not include XFG patients (with XFG 25.2±1.2 mm Hg and without XFG 24.3±1.0 mm Hg, P=0.016). Trial designs for prospective, parallel, glaucoma clinical studies that are performed in the United States generally can include PD and XFG patients with only a small impact on the IOP and a low number of such subjects enrolled.

A study of chemokines, chemokine receptors and interleukin-6 in patients with panic disorder, personality disorders and their co-morbidity.

PubMed

Ogłodek, Ewa A; Szota, Anna M; Just, Marek J; Szromek, Adam R; Araszkiewicz, Aleksander

2016-08-01

Stress may induce inflammatory changes in the immune system and activate pro-inflammatory cytokines and their receptors by activating the hypothalamic-pituitary-adrenal axis. 460 hospitalized patients with panic disorders (PD) and/or personality disorders (P) were studied. The study group comprised subjects with PD, avoidant personality disorder (APD), borderline personality disorder (BPD), obsessive-compulsive personality disorder (OCPD), and concomitant (PD+APD; PD+BPD; PD+OCPD). Each study group consisted of 60 subjects (30 females and 30 males). The control group included 20 females and 20 males without any history of mental disorder. ELISA was used to assess the levels of chemokines: CCL-5/RANTES (regulated on activation, normal T-cell expressed and secreted), CXCL-12/SDF-1 (stromal derived factor), their receptors CXCR-5 (C-C chemokine receptor type-5), CXCR-4 (chemokine C-X-C motif receptor-4), and IL-6. Statistically significant differences in the levels of CCL-5 and CCR-5 were revealed between all study groups. The greatest differences were found between the groups with PD+OCPD and PD+APD. Moreover, concomitance of PD with P significantly increased the level of chemokines and their receptors in all study groups versus the subjects with P alone. The results of the study show differences between the groups. To be specific, inflammatory markers were more elevated in the study groups than the controls. Therefore, chemokines and chemokine receptors may be used as inflammatory markers in patients with PD co-existent with P to indicate disease severity. PD was found to be a factor in maintaining inflammatory activity in the immune system in patients with P. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Increased suicide risk and clinical correlates of suicide among patients with Parkinson's disease.

PubMed

Lee, Taeyeop; Lee, Hochang Benjamin; Ahn, Myung Hee; Kim, Juyeon; Kim, Mi Sun; Chung, Sun Ju; Hong, Jin Pyo

2016-11-01

Parkinson's disease (PD) is a debilitating, neurodegenerative condition frequently complicated by psychiatric symptoms. Patients with PD may be at higher risk for suicide than the general population, but previous estimates are limited and conflicting. The aim of this study is to estimate the suicide rate based on the clinical case registry and to identify risk factors for suicide among patients diagnosed with PD. The target sample consisted of 4362 patients diagnosed with PD who were evaluated at a general hospital in Seoul, South Korea, from 1996 to 2012. The standardized mortality ratio for suicide among PD patients was estimated. In order to identify the clinical correlates of suicide, case-control study was conducted based on retrospective chart review. The 29 suicide cases (age: 62.3 ± 13.7 years; females: 34.5%) were matched with 116 non-suicide controls (age: 63.5 ± 9.2 years; females 56.9%) by the year of initial PD evaluation. The SMR for suicide in PD patients was 1.99 (95% CI 1.33-2.85). Mean duration from time of initial diagnosis to suicide among cases was 6.1 ± 3.5 years. Case-control analysis revealed that male, initial extremity of motor symptom onset, history of depressive disorder, delusion, any psychiatric disorder, and higher L-dopa dosage were significantly associated with suicide among PD patients. Other PD-related variables such as UPDRS motor score were not significantly associated with death by suicide. Suicide risk in PD patients is approximately 2 times higher than that in the general population. Psychiatric disorders, and also L-dopa medication need further attention with respect to suicide. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of programmed cell death protein 1 (PD-1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma.

PubMed

Kim, Kyu Seo; Sekar, Rishi R; Patil, Dattatraya; Dimarco, Michelle A; Kissick, Haydn T; Bilen, Mehmet A; Osunkoya, Adeboye O; Master, Viraj A

2018-01-01

Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have shown activity in patients with advanced renal cell carcinoma (RCC). However, the role of PD-1 expression in tumor-infiltrating lymphocytes (TILs) as a biomarker for poor outcome is not clear. In this study, we evaluated the prognostic value of TIL PD-1 expression in patients with clear cell RCC (ccRCC). 82 patients who underwent nephrectomy for localized or metastatic ccRCC and followed up for at least four years were searched from our database and retrospectively enrolled. Their fixed primary tumor specimens were stained with anti-PD-1 (NAT105). The specimens were classified as negative or positive for PD-1 expression, and the positive specimens were further scored in 10% increments. 37 (45.12%) patients were negative (<1% stained), 26 (31.71%) patients were low (<10 and 10%), and 19 (23.17%) patients were high (20-50%) for PD-1 expression. The prognostic value of TIL PD-1 expression was evaluated by univariate Cox proportional hazards regression on overall and recurrence-free survivals. Higher TIL PD-1 expression was not associated with increased risk of death (P = 0.336) or with increased risk of recurrence (P = 0.572). Higher primary tumor stage was associated with increased risk of recurrence (P = 0.003), and higher Fuhrman nuclear grade was associated with increased risk of death (P <0.001) and with increased risk of recurrence (P <0.001). Our study shows that TIL PD-1 expression by immunohistochemistry (IHC) does not correlate with poor clinical outcome in patients with ccRCC and is inferior to established prognosticating tools.

Body mass index in Parkinson's disease: a meta-analysis.

PubMed

van der Marck, Marjolein A; Dicke, Heleen C; Uc, Ergun Y; Kentin, Zippora H A; Borm, George F; Bloem, Bastiaan R; Overeem, Sebastiaan; Munneke, Marten

2012-03-01

Prior work suggested that patients with Parkinson's disease (PD) have a lower Body Mass Index (BMI) than controls, but evidence is inconclusive. We therefore conducted a meta-analysis on BMI in PD. We searched MEDLINE, EMBASE, Cinahl and Scopus to identify cohort studies on BMI in PD, published before February 2011. Studies that reported mean BMI for PD patients and healthy controls were eligible. Twelve studies were included, with a total of 871 patients and 736 controls (in three studies controls consisted of subjects from other published studies). Our primary aim was to assess differences in BMI between patients and controls; this was analyzed with random effects meta-analysis. Our secondary aim was to evaluate the relation with disease severity (Hoehn and Yahr stage) and disease duration, using random effects meta-regression. PD patients had a significantly lower BMI than controls (overall effect 1.73, 95% CI 1.11-2.35, P<0.001). Pooled data of seven studies showed that patients with Hoehn and Yahr stage 3 had a lower BMI than patients with stage 2 (3.9, 95% CI 0.1-7.7, P<0.05). Disease duration was not associated with BMI. Because a low body weight is associated with negative health effects and a poorer prognosis, monitoring weight and nutritional status should be part of PD management. Copyright © 2011. Published by Elsevier Ltd.

Peritonitis in children with automated peritoneal dialysis: a single-center study of a 10-year experience.

PubMed

Dotis, John; Myserlis, Pavlos; Printza, Nikoleta; Stabouli, Stella; Gkogka, Chrysa; Pavlaki, Antigoni; Papachristou, Fotios

2016-08-01

Peritoneal dialysis (PD) constitutes the preferred dialysis modality for children requiring renal replacement therapy with peritonitis being one of the most common complications of PD. This study was performed to evaluate the epidemiology, microbiology, and outcomes of PD-associated peritonitis in Greek children for a 10-year period. A total of 27 patients (16 males) with a mean age 121.8 ± 57.2 months were retrospective analyzed. Patients were on PD therapy for a mean duration of 45.2 ± 26.1 months. We found 23 episodes of PD-associated peritonitis occurred in 9 out of 27 patients (0.23 episodes/patient-year), with four patients experienced two or more peritonitis episodes. Gram-positive bacteria were responsible for 15 (65.2%) peritonitis episodes, with Staphylococcus aureus being the predominant specie isolated in 30.4% of cases. A total of seven episodes of exit-site infections (ESIs) were identified in five patients (0.069 episodes/patient-year) with the most common bacteria isolated being S. aureus (57.4%). Initial antibiotic treatment included intraperitoneal vancomycin plus ceftazidime in the majority of cases (82.6%). At the end of study, 12 (44.4%) patients remained on PD, 11 (41.8%) underwent renal transplantation, 2 (7.4%) shifted to hemodialysis and unfortunately, two patients (7.4%) died. Conclusively, our study revealed a noticeable low peritonitis and ESIs rate as compared to international data and represents the first evaluation of the characteristics and outcomes of peritonitis in the Greek pediatric PD population.

Falls in ambulatory non-demented patients with Parkinson's disease.

PubMed

Rascol, Olivier; Perez-Lloret, Santiago; Damier, Philippe; Delval, Arnaud; Derkinderen, Pascal; Destée, Alain; Meissner, Wassilios G; Tison, Francois; Negre-Pages, Laurence

2015-10-01

This study aimed at determining the prevalence of falling in PD patients, to assess generic and disease-specific clinical and pharmacological factors, relationship with health-related quality of life (HR-QoL) and changes in falls from OFF to ON in patients with motor fluctuations. Six-hundred and eighty-three PD patients of the COPARK survey were evaluated (11 had missing data and were excluded from the analysis). Patients with falls were identified as those with a UPDRS Item 13 ≥ 1 in the ON condition. All patients were assessed in a standardized manner [demographics, treatments, Unified PD Rating Scale (UPDRS), Hospital Anxiety and Depression Scale, Pittsburg questionnaire and HR-QoL scales (SF36, PDQ39)]. Falling was reported by 108/672 (16%) PD patients during the ON state and prevalence increased according to PD severity, from 5% in Hoehn and Yahr stage 1-60% in stage 4. Falling was significantly related to lower HR-QoL. Falling correlated with (1) generic factors such as female gender, age at the end of academic studies and diuretics consumption, (2) motor PD-specific factors including disease severity, frozen gait, difficulties when arising from a chair, dyskinesia and higher levodopa daily equivalent dose and (3) non-motor PD-specific factors such as orthostatic hypotension and hallucinations. Falling was more frequent in OFF than in ON in 48/74 (64%) patients with motor fluctuations and remained unchanged in 27 patients (36%). In summary, falling affected a significant proportion of PD patients, especially in advanced stages. It was associated with a variety of generic and PD-specific factors and was related to reduced HR-QoL.

The efficacy of a neonatal screening programme in decreasing the hospitalization rate of patients with G6PD deficiency in southern Iran.

PubMed

Cohan, Nader; Karimi, Mehran; Khalili, Amir Hossein; Falahzadeh, Mohammad Hossein; Samadi, Behrang; Mahdavi, Mohammad Reza

2010-01-01

To investigate whether a neonatal screening programme for G6PD deficiency has decreased hospitalization for acute haemolytic attack in the Fars province of southern Iran. A total of 850 patients registered with G6PD deficiency were included in the study. Variables including age, sex, time and cause of hospitalization, cause of haemolytic crisis, positive history of blood transfusion, G6PD enzyme deficiency, blood urea nitrogen (BUN) and creatinine were recorded based on a standard questionnaire. All patients were analysed for G6PD enzyme level based on a quantitative test. Five hundred and fifty-three patients were hospitalized before the introduction of the neonatal screening programme (2001-2004) and 297 afterwards (2005-2008). Of those patients hospitalized after the introduction of the screening programme, 237 were wrongly classified as normal and 60 were recorded as having G6PD enzyme deficiency by the neonatal screening programme. The main causes of haemolytic crisis in G6PD-deficient patients were fava bean consumption (88.2%), underlying infection (10.9%) and drugs (0.8%). Our study showed the effectiveness of the neonatal screening programme in decreasing the hospitalization rate.

Pneumatic balloon dilation in pediatric achalasia: efficacy and factors predicting outcome at a single tertiary pediatric gastroenterology center.

PubMed

Di Nardo, Giovanni; Rossi, Paolo; Oliva, Salvatore; Aloi, Marina; Cozzi, Denis A; Frediani, Simone; Redler, Adriano; Mallardo, Saverio; Ferrari, Federica; Cucchiara, Salvatore

2012-11-01

The use of pneumatic dilation (PD) is well established in adults with achalasia; however, it is less commonly used in children. To evaluate the efficacy of PD in pediatric achalasia and to define predictive factors for its treatment failure. Single-center, prospective cohort study. Academic tertiary referral center. Twenty-four patients with achalasia were enrolled from January 2004 to November 2009 and were followed for a median of 6 years. PD was performed with the patients under general anesthesia. Efficacy and safety of PD. Follow-up was performed by using the Eckardt score, barium swallow contrast studies, and esophageal manometry at baseline; 1, 3, and 6 months after dilation; and every year thereafter. A Cox regression model was used to identify independent predictors of failure after the first PD. The PD success rate was 67%. In 8 patients, the first PD failed, but the parents of one patient refused a second PD and requested surgery. Of the 7 patients who underwent repeated treatment, the second PD failed in 3 (43%). Overall, only 3 of the 24 patients underwent surgery (overall success rate after a maximum of 3 PDs was 87%). Multivariate analysis showed that only older age was independently associated with a higher probability of the procedure success (hazard ratio [HR] 0.66; 95% CI, 0.45-0.97). Small sample size, single-center study. PD is a safe and effective technique in the management of pediatric achalasia. Young age is an independent negative predictive factor for successful clinical outcome. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Role of habenula and amygdala dysfunction in Parkinson disease patients with punding.

PubMed

Markovic, Vladana; Agosta, Federica; Canu, Elisa; Inuggi, Alberto; Petrovic, Igor; Stankovic, Iva; Imperiale, Francesca; Stojkovic, Tanja; Kostic, Vladimir S; Filippi, Massimo

2017-06-06

To assess whether a functional dysregulation of the habenula and amygdala, as modulators of the reward brain circuit, contributes to Parkinson disease (PD) punding. Structural and resting-state functional MRI were obtained from 22 patients with PD punding, 30 patients with PD without any impulsive-compulsive behavior (ICB) matched for disease stage and duration, motor impairment, and cognitive status, and 30 healthy controls. Resting-state functional connectivity of the habenula and amygdala bilaterally was assessed using a seed-based approach. Habenula and amygdala volumes and cortical thickness measures were obtained. Compared to both healthy controls and PD cases without any ICB (PD-no ICB), PD-punding patients showed higher functional connectivity of habenula and amygdala with thalamus and striatum bilaterally, and lower connectivity between bilateral habenula and left frontal and precentral cortices. In PD-punding relative to PD-no ICB patients, a lower functional connectivity between right amygdala and hippocampus was also observed. Habenula and amygdala volumes were not different among groups. PD-punding patients showed a cortical thinning of the left superior frontal and precentral gyri and right middle temporal gyrus and isthmus cingulate compared to healthy controls, and of the right inferior frontal gyrus compared to both controls and PD-no ICB patients. A breakdown of the connectivity among the crucial nodes of the reward circuit (i.e., habenula, amygdala, basal ganglia, frontal cortex) might be a contributory factor to punding in PD. This study provides potential instruments to detect and monitor punding in patients with PD. © 2017 American Academy of Neurology.

Laryngeal electromyography as a diagnostic tool for Parkinson's disease.

PubMed

Zarzur, Ana P; Duprat, André de Campos; Cataldo, Berenice O; Ciampi, Daniel; Fonoff, Erich

2014-03-01

To study the laryngeal electromyography pattern in patients with Parkinson's disease (PD) and vocal complaints at different stages of the disease. Cross-sectional cohort study. Ninety-four adults with PD and vocal complaints at different stages of the disease (according to the Hoehn and Yahr scale) underwent laryngeal electromyography. Tremors were not detected on laryngeal electromyography of the cricothyroid and thyroarytenoid muscles even in patients with clinical tremor. Laryngeal electromyography hypercontractility during voice rest was the typical result observed in 91.5% of patients regardless of disease severity. Gender and age of subjects did not correlate with laryngeal electromyography results. Patients with PD presented spontaneous intrinsic laryngeal muscle activity during voice rest, regardless of disease severity. This study was significant because it reported on the use of laryngeal electromyography in a large number of patients with PD and vocal complaints grouped according to PD severity. The patterns observed suggest that laryngeal electromyography is a valuable diagnostic tool for PD even at early phases of the disease. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Circulating and tumor-infiltrating Tim-3 in patients with colorectal cancer

PubMed Central

Gao, Quanli; Yuan, Peng; Zhao, Peng; Yuan, Huijuan; Fan, Huijie; Li, Tiepeng; Qin, Peng; Han, Lu; Fang, Weijia; Suo, Zhenhe

2015-01-01

T-cell exhaustion represents a progressive loss of T-cell function. The inhibitory receptor PD-1 is known to negatively regulate CD8+ T cell responses directed against tumor antigen, but the blockades of PD-1 pathway didn't show the objective responses in patients with colorectal cancer (CRC). Thus, further exploring the molecular mechanism responsible for inducing T-cell dysfunction in CRC patients may reveal effective strategies for immune therapy. This study aims to characterize co-inhibitory receptors on T cells in CRC patients to identify novel targets for immunotherapy. In this study, peripheral blood samples from 20 healthy controls and 54 consented CRC patients, and tumor and matched paraneoplastic tissues from 7 patients with advanced CRC, subjected to multicolor flow cytometric analysis of the expression of PD-1 and Tim-3 receptors on CD8+ T cells. It was found that CRC patients presented with significantly higher levels of circulating Tim-3+PD-1+CD8+ T cells compared to the healthy controls (medians of 3.12% and 1.99%, respectively, p = 0.0403). A similar increase of Tim-3+PD-1+CD8+ T cells was also observed in the tumor tissues compared to paraneoplastic tussues. Tim-3+PD-1+CD8+ T cells in tumor tissues produced even less cytokine than that in paraneoplastic tissues. Functional ex vivo experiments showed that Tim-3+PD-1+CD8+ T cells produced significantly less IFN-γ than Tim-3−PD-1−CD8+ T cells, followed by Tim-3+PD-1−CD8+ T cells, and Tim-3−PD-1+CD8+ T cells, indicating a stronger inhibition of IFN-γ production of Tim-3+CD8+ T cells. It is also found in this study that Tim-3+PD-1+CD8+ T cell increase in circulation was correlated with clinical cancer stage but not histologic grade and serum concentrations of cancer biomarker CEA. Our results indicate that upregulation of the inhibitory receptor Tim-3 may restrict T cell responses in CRC patients, and therefore blockage of Tim-3 and thus restoring T cell responses may be a potential therapeutic approach for CRC patients. PMID:26008981

Progressive deficit in isolated pontine infarction: the association with etiological subtype, lesion topography and outcome.

PubMed

Gökçal, Elif; Niftaliyev, Elvin; Baran, Gözde; Deniz, Çiğdem; Asil, Talip

2017-09-01

It is important to predict progressive deficit (PD) in isolated pontine infarction, a relatively common problem of clinical stroke practice. Traditionally, lacunar infarctions are known with their progressive course. However, few studies have analyzed the branch atheromatous disease subtype as a subtype of lacunar infarction, separately. There are also conflicting results regarding the relationship with the topography of lesion and PD. In this study, we classified etiological subtypes and lesion topography in isolated pontine infarction and aimed to investigate the association of etiological subtypes, lesion topography and clinical outcome with PD. We analyzed demographics, laboratory parameters, and risk factors of 120 patients having isolated pontine infarction and admitted within 24 h retrospectively. PD was defined as an increase in the National Institutes of Health Stroke scale ≥2 units in 5 days after onset. Patients were classified as following: large artery disease (LAA), basilar artery branch disease (BABD) and small vessel disease (SVD). Upper, middle and lower pontine infarcts were identified longitudinally. Functional outcome at 3 months was determined according to modified Rankin scores. Of 120 patients, 41.7% of the patients were classified as BABD, 30.8% as SVD and 27.5% as LAA. 23 patients (19.2%) exhibited PD. PD was significantly more frequent in patient with BABD (p 0.006). PD was numerically higher in patients with lower pontine infarction. PD was associated with BABD and poor functional outcome. It is important to discriminate the BABD neuroradiologically from other stroke subtypes to predict PD which is associated with poor functional outcome in patients with isolated pontine infarctions.

Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease

PubMed Central

Evatt, Marian L.; DeLong, Mahlon R.; Khazai, Natasha; Rosen, Ami; Triche, Shirley; Tangpricha, Vin

2009-01-01

Background A role for vitamin D deficiency in Parkinson disease (PD) has recently been proposed. Objective To compare the prevalence of vitamin D deficiency in a research database cohort of patients with PD with the prevalence in age-matched healthy controls and patients with Alzheimer disease (AD). Design Survey study and blinded comparison of plasma 25-hydroxyvitamin D (25[OH]D) concentrations of stored samples in a clinical research database at Emory University School of Medicine. Setting Referral center (PD and AD patients), primary care clinics, and community setting (controls). Participants Participants were recruited into the study between May 1992 and March 2007. Every fifth consecutively enrolled PD patient was selected from the clinical research database. Unrelated AD (n=97) and control (n=99) participants were randomly selected from the database after matching for age, sex, race, APOE genotype, and geographic location. Main Outcome Measures Prevalence of suboptimal vitamin D and mean 25(OH)D concentrations. Results Significantly more patients with PD (55%) had insufficient vitamin D than did controls (36%) or patients with AD (41%; P=.02, χ2 test). The mean (SD) 25(OH)D concentration in the PD cohort was significantly lower than in the AD and control cohorts (31.9 [13.6] ng/mL vs 34.8 [15.4] ng/mL and 37.0 [14.5] ng/mL, respectively; P=.03). Conclusions This report of 25(OH)D concentrations in a predominantly white PD cohort demonstrates a significantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD. These data support a possible role of vitamin D insufficiency in PD. Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of PD. PMID:18852350

Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response.

PubMed

Holmström, Morten Orebo; Riley, Caroline Hasselbalch; Skov, Vibe; Svane, Inge Marie; Hasselbalch, Hans Carl; Andersen, Mads Hald

2018-01-01

The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4 + T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity.

Psychogenic and neural visual-cue response in PD dopamine dysregulation syndrome.

PubMed

Loane, Clare; Wu, Kit; O'Sullivan, Sean S; Lawrence, Andrew D; Woodhead, Zoe; Lees, Andrew J; Piccini, Paola; Politis, Marios

2015-11-01

Dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) patients refers to the compulsive use of dopaminergic replacement therapy and has serious psycho-social consequences. Mechanisms underlying DDS are not clear although has been linked to dysfunctional brain reward networks. With fMRI, we investigate behavioral and neural response to drug-cues in six PD DDS patients and 12 PD control patients in both the ON and OFF medication state. Behavioral measures of liking, wanting and subjectively 'feeling ON medication' were also collected. Behaviorally, PD DDS patients feel less ON and want their drugs more at baseline compared to PD controls. Following drug-cue exposure, PD DDS patients feel significantly more ON medication, which correlates with significant increases in reward related regions. The results demonstrate that exposure to drug-cues increases the subjective feeling of being 'ON' medication which corresponds to dysfunctional activation in reward related regions in PD DDS patients. These findings should be extended in future studies. Visual stimuli being sufficient to elicit behavioral response through neuroadaptations could have direct implications to the management of addictive behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dreaming and cognition in patients with frontotemporal dysfunction.

PubMed

Paiva, Teresa; Bugalho, Paulo; Bentes, Carla

2011-12-01

Individuals with Parkinson's disease (PD) and temporal lobe epilepsy (TLE) have hallucinations and mild cognitive dysfunction. The objective of this work was to study dreams in PD and TLE patients using a common functional model of dream production involving the limbic and paralimbic structures. Dreams were characterised in early-stage PD (19 males) and TLE patients (52) with dream diaries classified by the Hall van de Castle system and were compared with matched controls. In PD, there were significant differences between patients' dreams and those of controls: animals, physical aggression, and a befriender were more common in patients, and aggressor and bodily misfortunes were less common. The dreams of patients with frontal dysfunction showed more aggressive features. TLE patients had lower recall than PD patients and a higher proportion of dreams involving family and familiar settings, lower proportions involving success, and a higher incidence of frontal dysfunction. The dreams of PD and TLE patients share important features. Copyright © 2011. Published by Elsevier Inc.

Peyronie's disease intervention trials: methodological challenges and issues.

PubMed

Müller, Alexander; Mulhall, John P

2009-03-01

Peyronie's Disease (PD) has been studied for more than 260 years since Francois de la Peyronie's description in 1743. Based on the current literature, the prevalence of PD seems 3-9% with an average age of onset in the fifth life decade. Much effort has been spent on developing nonsurgical treatment options to cure or at least prevent disease progression. The recent examination of drug trials for erectile dysfunction has led us to assess PD trial methodology more closely. An Iinternet search on PubMed was performed using MeSH words PD, clinical trials, oral, transdermal, intralesional and shock wave therapy focusing on 26 representing studies published over the last 15 years. Mean Outcome Measures. A comprehensive review of the current literature on nonsurgical treatment options for PD was conducted to address methodological issues and challenges in PD trials highlighting trial design, patient population, and symptom and sign assessment. The majority of the reviewed studies are underpowered and the heterogeneity in the methodological approach and patient assessment between the studies is one of the remarkable findings from our review. Studies should use a uniform means of defining the degree and type of penile deformity and a large enough cohort of patients should be studied for adequate study power. An ideally designed PD intervention trial should comprise: (i) a randomized, placebo-controlled design; (ii) with a PD patient set representative of the general PD population; and (iii) a comprehensive symptom and sign assessment before and at the end of treatment which includes an assessment of at least deformity, pain, and sexual function. A number of challenges exist for the design of PD intervention trials and deciphering the data generated from them. The field would benefit greatly from a consensus statement or guidelines development on the design and conduct of such trials.

Risk Factor Profile in Parkinson's Disease Subtype with REM Sleep Behavior Disorder.

PubMed

Jacobs, Marie L; Dauvilliers, Yves; St Louis, Erik K; McCarter, Stuart J; Romenets, Silvia Rios; Pelletier, Amélie; Cherif, Mahmoud; Gagnon, Jean-François; Postuma, Ronald B

2016-01-01

Numerous large-scale studies have found diverse risk factors for Parkinson's disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep behavior disorder (RBD).In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. To define risk factors for PD in patients with or without associated RBD. In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05-9.223), and to have been regular smokers (OR = 1.96 (1.04-3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07-10.0). The RBD-specific subtype of PD may also have a different risk factor profile.

Barriers to Increasing Use of Peritoneal Dialysis in Bangladesh: A Survey of Patients and Providers.

PubMed

Savla, Dipal; Ahmed, Sweety; Yeates, Karen; Matthew, Anna; Anand, Shuchi

2017-01-01

Despite a lower requirement for technology and equipment than hemodialysis (HD), peritoneal dialysis (PD) is an underutilized modality in low- and middle-income countries (LMICs). Bangladesh has the lowest use of PD in the world (fewer than 2% of prevalent patients). We evaluated nephrologists' attitudes toward PD and examined differences between patients on HD and PD in Dhaka. We asked nephrologists to fill out an English-language questionnaire. Using convenience sampling but targeting both public and private hospitals in Dhaka, we asked trained nurses to administer a Bangla-language questionnaire to patients on HD ( n = 116) and PD ( n = 41). We validated the questionnaires on a sub-sample ( n = 10 for each group). Of the 43 nephrologists surveyed, 27 (63%) had patients on PD. When compared with nephrologists without patients on PD, those with patients on PD were less likely to believe that survival and quality of life on PD was worse than on HD (odds ratio [OR] = 0.21, 95% confidence interval [CI] 0.05 - 0.83 and OR = 0.11, 95% CI 0.02 - 0.67 respectively) but were not more likely to have received training for PD. Nephrologists named cost of PD as the predominant barrier to increasing use of PD, followed by concerns about patient hygiene and lack of trained nurses. Fifty-two HD patients (45%) did not know about a home-based modality. When compared with patients on HD, patients on PD were more likely to have been educated by non-nephrologists about dialysis, to be "forewarned" about the need for dialysis, to be paying fully, and to be living in a permanent home with a non-communal water source. Some barriers to increasing access to PD-i.e., patient living conditions and cost-are unique to LMICs. Our study also highlights that issues encountered in high-income countries-i.e., nephrologists' subjective preference and lack of patient knowledge about an alternate modality to HD-may play a role as well. Copyright © 2017 International Society for Peritoneal Dialysis.

PD-L1 expression is associated with p16INK4A expression in non-oropharyngeal head and neck squamous cell carcinoma

PubMed Central

Chen, San-Chi; Chang, Peter Mu-Hsin; Wang, Hsiao-Jung; Tai, Shyh-Kuan; Chu, Pen-Yuan; Yang, Muh-Hwa

2018-01-01

PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16INK4A expression were determined using immunohistochemistry. Systemic inflammatory factors, including C-reactive protein, serum white blood cell, neutrophil, monocyte and lymphocyte counts were also analyzed. The current study demonstrated that PD-L1 was overexpressed in 32.1% (34/106) and p16INK4A in 20.8% (22/106) of patients. The expression of PD-L1 was associated with p16INK4A expression (P<0.01) but was not associated with levels of systemic inflammatory factors. Tumor stage was determined to be a significant prognostic value (stage I/II vs. III/IV, P=0.03), however, PD-L1, p16INK4A or other clinicopathological factors were not. The current study identified an association between PD-L1 and p16INK4A expression in non-OPHNSCC. This may facilitate the development of anti-PD1/PDL1 therapies to treat patients with head and neck cancer. PMID:29434933

Identification of Mediterranean mutation in Egyptian favism patients.

PubMed

Osman, H G; Zahran, F M; El-Sokkary, A M A; El-Said, A; Sabry, A M

2014-10-01

Identify and screen the G6PD Mediterranean mutation in favism patients by applying a Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR). A total of 114 unrelated Egyptians patients were included in the present study; their ages ranged between (2-9) years with male to female ratio 4.5:1. G6PD activity was determined qualitatively from red cell hemolysate during attack. The G6PD Mediterranean mutation in patients has been identified by ARMS-PCR. G6PD deficiency was detected in 87.7%, (n=100). The frequency of G6PD Mediterranean mutation was (94.7%), (n=108). The association between G6PD deficiency and Mediterranean mutation was a highly significant. Glucose-6-phosphate dehydrogenase Mediterranean mutation is one of the most common mutations causing G6PD deficiency among Egyptian children with favism.

Comparison of peritoneal dialysis and hemodialysis after kidney transplant failure.

PubMed

Kang, G W; Jang, M H; Hwang, E A; Park, S B; Han, S Y

2013-10-01

Patients with a failed kidney transplant represent a unique chronic kidney disease population that is increasing in number and is at high risk of morbidity and mortality. Among transplant-naïve patients, those treated with peritoneal dialysis (PD) show an early survival advantage compared with those treated with hemodialysis (HD). But any advantage of PD after allograft failure is unknown. The aim of this study was to investigate the clinical outcomes of patients with failed allografts according to the type of dialysis modality. We reviewed medical records of patients who initiated dialysis after kidney transplant failure from November 1982 to May 2011. Demographics features, clinical data, and survival outcomes were compared between PD and HD patients who had experienced allograft failure. The 182 patients with failed allografts showed the most common cause to be chronic rejection. The median duration of function before allograft failure was 74.0 months. After allograft failure, 145 (79.7%) patients returned to HD and 37 (20.3%) to PD. Twenty-three patients (12.6%) died over the median 69.1 months duration of follow-up. During the observation period, 16 HD (11%) and 7 PD (8.9%) patients died. The survival rates of PD patients at 1 year were 91.2% and 84.4%, respectively, at 1 and 3 years, and those of HD patients 94.8% and 88.9%. There was no significant difference in the survivals of the 2 groups. The study suggests that the outcome of patients starting PD after kidney transplant failure was similar to those starting HD. Therefore, PD can be regarded to be a good treatment option for patients returning to dialysis after kidney transplant failure. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

The impact of transfer from hemodialysis on peritoneal dialysis technique survival.

PubMed

Nessim, Sharon J; Bargman, Joanne M; Jassal, S Vanita; Oliver, Matthew J; Na, Yingbo; Perl, Jeffrey

2015-01-01

A significant proportion of peritoneal dialysis (PD) patients receive an initial period of hemodialysis (HD) before transitioning to PD ("PD-switch"). We sought to better understand the risks of PD technique failure (TF) and mortality for those patients compared with patients starting with PD as their first dialysis modality ("PD-first"). Using Canadian Organ Replacement Register data, we compared the risk of PD TF between PD-first and PD-switch patients within the first year after HD initiation. In a secondary analysis, the PD-switch patients were stratified into three groups based on timing of the switch from initial HD to PD as follows: 0 - 90 days, 91 - 180 days, and 181 - 365 days. Each group was compared with PD-first patients for risk of PD TF and death. Between 2001 and 2010, 9404 patients initiated PD as their first renal replacement therapy, and 3757 switched from HD to PD. After multivariable adjustment, the risk of PD TF was higher among PD-switch patients than among PD-first patients [adjusted hazard ratio (AHR): 1.37; 95% confidence interval (CI): 1.26 to 1.49], particularly within the first year after the switch from HD to PD (AHR: 1.51; 95% CI: 1.36 to 1.68). There was no association between time on HD within the first year and subsequent risk of PD TF. For all the stratified PD-switch groups, death rates were higher than those for PD-first patients. Compared with patients who start renal replacement therapy with PD, those who transfer from HD to PD within the first year on dialysis experience higher rates of PD TF and death, with the highest risk being observed in the initial year after the switch to PD. Copyright © 2015 International Society for Peritoneal Dialysis.

Diagnosing mild cognitive impairment in Parkinson's disease: which tests perform best in the Italian population?

PubMed

Federico, Angela; Trentin, Michela; Zanette, Giampietro; Mapelli, Daniela; Picelli, Alessandro; Smania, Nicola; Tinazzi, Michele; Tamburin, Stefano

2017-08-01

Mild cognitive impairment (MCI) is common in patients with Parkinson's disease (PD) and should be recognized early because it represents a predictor of PD-related dementia and worse disease course. Diagnostic criteria for PD-related MCI (PD-MCI) have recently been defined by a Movement Disorders Society (MDS) task force. The present study explored which neuropsychological tests perform best for a level II (i.e., comprehensive neuropsychological assessment) diagnosis of PD-MCI according to the MDS task force criteria in Italian-speaking PD patients. To this aim, we assessed a comprehensive 23-item neuropsychological battery, derived the best-performing 10-test battery (i.e., two tests per domain for each of the five cognitive domains), and explored its accuracy for diagnosing PD-MCI in comparison to the full battery in a group of PD patients. A secondary aim was to explore the role of this battery for subtyping PD-MCI according to single-domain vs. multiple-domain involvement. The 10-test battery showed 73% sensitivity and 100% specificity for diagnosing PD-MCI, and 69% sensitivity and 100% specificity for PD-MCI subtyping. In patients older than 70 years, we derived a slightly different 10-test battery with 84% sensitivity and 100% specificity for PD-MCI diagnosis, and 86% sensitivity and 100% specificity for PD-MCI subtyping. These 10-item neuropsychological batteries might represent a good trade-off between diagnostic accuracy and time of application, and their role in PD-MCI diagnosis and subtyping should be further explored in future prospective studies.

Walking economy in people with Parkinson's disease.

PubMed

Christiansen, Cory L; Schenkman, Margaret L; McFann, Kim; Wolfe, Pamela; Kohrt, Wendy M

2009-07-30

Gait dysfunction is an early problem identified by patients with Parkinson's disease (PD). Alterations in gait may result in an increase in the energy cost of walking (i.e., walking economy). The purpose of this study was to determine whether walking economy is atypical in patients with PD when compared with healthy controls. A secondary purpose was to evaluate the associations of age, sex, and level of disease severity with walking economy in patients with PD. The rate of oxygen consumption (VO(2)) and other responses to treadmill walking were compared in 90 patients (64.4 +/- 10.3 years) and 44 controls (64.6 +/- 7.3 years) at several walking speeds. Pearson correlation coefficients (r) were calculated to determine relationships of age, sex, and disease state with walking economy in PD patients. Walking economy was significantly worse in PD patients than in controls at all speeds above 1.0 mph. Across all speeds, VO(2) was 6 to 10% higher in PD patients. Heart rate, minute ventilation, respiratory exchange ratio, and rating of perceived exertion were correspondingly elevated. No significant relationship of age, sex, or UPDRS score with VO(2) was found for patients with PD. The findings suggest that the physiologic stress of daily physical activities is increased in patients with early to mid-stage PD, and this may contribute to the elevated level of fatigue that is characteristic of PD. Copyright 2009 Movement Disorder Society.

Fine Motor Function Skills in Patients with Parkinson Disease with and without Mild Cognitive Impairment.

PubMed

Dahdal, Philippe; Meyer, Antonia; Chaturvedi, Menorca; Nowak, Karolina; Roesch, Anne D; Fuhr, Peter; Gschwandtner, Ute

2016-01-01

The objective of this study was to investigate the relation between impaired fine motor skills in Parkinson disease (PD) patients and their cognitive status, and to determine whether fine motor skills are more impaired in PD patients with mild cognitive impairment (MCI) than in non-MCI patients. Twenty PD MCI and 31 PD non-MCI patients (mean age 66.7 years, range 50-84, 36 males/15 females), all right-handed, took part in a motor performance test battery. Steadiness, precision, dexterity, velocity of arm-hand movements, and velocity of wrist-finger movements were measured and compared across groups and analyzed for confounders (age, sex, education, severity of motor symptoms, and disease duration). Statistical analysis included t tests corrected for multiple testing, and a linear regression with stepwise elimination procedure was used to select significant predictors for fine motor function. PD MCI patients performed significantly worse in precision (p < 0.05), dexterity (p < 0.05), and velocity (arm-hand movements; p < 0.05) compared to PD non-MCI patients. The fine motor function skills were confounded by age. Fine motor skills in PD MCI patients are impaired compared to PD non-MCI patients. Investigating the relation between the fine motor performance and MCI in PD might be a relevant subject for future research. © 2016 S. Karger AG, Basel.

Impact of Personality Disorder Cluster on Depression Outcomes Within Collaborative Care Management Model of Care.

PubMed

George, Merit P; Garrison, Gregory M; Merten, Zachary; Heredia, Dagoberto; Gonzales, Cesar; Angstman, Kurt B

2018-01-01

Previous studies have suggested that having a comorbid personality disorder (PD) along with major depression is associated with poorer depression outcomes relative to those without comorbid PD. However, few studies have examined the influence of specific PD cluster types. The purpose of the current study is to compare depression outcomes between cluster A, cluster B, and cluster C PD patients treated within a collaborative care management (CCM), relative to CCM patients without a PD diagnosis. The overarching goal was to identify cluster types that might confer a worse clinical prognosis. This retrospective chart review study examined 2826 adult patients with depression enrolled in CCM. The cohort was divided into 4 groups based on the presence of a comorbid PD diagnosis (cluster A/nonspecified, cluster B, cluster C, or no PD). Baseline clinical and demographic variables, along with 6-month follow-up Patient Health Questionnaire-9 (PHQ-9) scores were obtained for all groups. Depression remission was defined as a PHQ-9 score <5 at 6 months, and persistent depressive symptoms (PDS) was defined as a PHQ-9 score ≥10 at 6 months. Adjusted odds ratios (AORs) were determined for both remission and PDS using logistic regression modeling for the 6-month PHQ-9 outcome, while retaining all study variables. A total of 59 patients (2.1%) had a cluster A or nonspecified PD diagnosis, 122 patients (4.3%) had a cluster B diagnosis, 35 patients (1.2%) had a cluster C diagnosis, and 2610 patients (92.4%) did not have any PD diagnosis. The presence of a cluster A/nonspecified PD diagnosis was associated with a 62% lower likelihood of remission at 6 months (AOR = 0.38; 95% CI 0.20-0.70). The presence of a cluster B PD diagnosis was associated with a 71% lower likelihood of remission at 6 months (AOR = 0.29; 95% CI 0.18-0.47). Conversely, having a cluster C diagnosis was not associated with a significantly lower likelihood of remission at 6 months (AOR = 0.83; 95% CI 0.42-1.65). Increased odds of having PDS at 6-month follow-up were seen with cluster A/nonspecified PD patients (AOR = 3.35; 95% CI 1.92-5.84) as well as cluster B patients (AOR = 3.66; 95% CI 2.45-5.47). However, cluster C patents did not have significantly increased odds of experiencing persistent depressive symptoms at 6-month follow-up (AOR = 0.95; 95% CI 0.45-2.00). Out of the 3 clusters, the presence of a cluster B PD diagnosis was most significantly associated with poorer depression outcomes at 6-month follow-up, including reduced remission rates and increased risk for PDS. The cluster A/nonspecified PD group also showed poor outcomes; however, the heterogeneity of this subgroup with regard to PD features must be noted. The development of novel targeted interventions for at-risk clusters may be warranted in order to improve outcomes of these patients within the CCM model of care.

Dialysis Modality and Readmission Following Hospital Discharge: A Population-Based Cohort Study.

PubMed

Perl, Jeffrey; McArthur, Eric; Bell, Chaim; Garg, Amit X; Bargman, Joanne M; Chan, Christopher T; Harel, Shai; Li, Lihua; Jain, Arsh K; Nash, Danielle M; Harel, Ziv

2017-07-01

Readmissions following hospital discharge among maintenance dialysis patients are common, potentially modifiable, and costly. Compared with patients receiving in-center hemodialysis (HD), patients receiving peritoneal dialysis (PD) have fewer routine dialysis clinic encounters and as a result may be more susceptible to a hospital readmission following discharge. Population-based retrospective-cohort observational study. Patients treated with maintenance dialysis who were discharged following an acute-care hospitalization during January 1, 2003, to December 31, 2013, across 164 acute-care hospitals in Ontario, Canada. For those with multiple hospitalizations, we randomly selected a single hospitalization as the index hospitalization. Dialysis modality PD or in-center HD. Propensity scores were used to match each patient on PD therapy to 2 patients on in-center HD therapy to ensure that baseline indicators of health were similar between the 2 groups. All-cause 30-day readmission following the index hospital discharge. 28,026 dialysis patients were included in the study. 4,013 PD patients were matched to 8,026 in-center HD patients. Among the matched cohort, 30-day readmission rates were 7.1 (95% CI, 6.6-7.6) per 1,000 person-days for patients on PD therapy and 6.0 (95% CI, 5.7-6.3) per 1,000 person-days for patients on in-center HD therapy. The risk for a 30-day readmission among patients on PD therapy was higher compared with those on in-center HD therapy (adjusted HR, 1.19; 95% CI, 1.08-1.31). The primary results were consistent across several key prespecified subgroups. Lack of information for the frequency of nephrology physician encounters following discharge from the hospital in both the PD and in-center HD cohorts. Limited validation of International Classification of Diseases, Tenth Revision codes. The risk for 30-day readmission is higher for patients on home-based PD compared to in-center HD therapy. Interventions to improve transitions in care between the inpatient and outpatient settings are needed, particularly for patients on PD therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Persian version of frontal assessment battery: Correlations with formal measures of executive functioning and providing normative data for Persian population.

PubMed

Asaadi, Sina; Ashrafi, Farzad; Omidbeigi, Mahmoud; Nasiri, Zahra; Pakdaman, Hossein; Amini-Harandi, Ali

2016-01-05

Cognitive impairment in patients with Parkinson's disease (PD) mainly involves executive function (EF). The frontal assessment battery (FAB) is an efficient tool for the assessment of EFs. The aims of this study were to determine the validity and reliability of the psychometric properties of the Persian version of FAB and assess its correlation with formal measures of EFs to provide normative data for the Persian version of FAB in patients with PD. The study recruited 149 healthy participants and 49 patients with idiopathic PD. In PD patients, FAB results were compared to their performance on EF tests. Reliability analysis involved test-retest reliability and internal consistency, whereas validity analysis involved convergent validity approach. FAB scores compared in normal controls and in PD patients matched for age, education, and Mini-Mental State Examination (MMSE) score. In PD patients, FAB scores were significantly decreased compared to normal controls, and correlated with Stroop test and Wisconsin Card Sorting Test (WCST). In healthy subjects, FAB scores varied according to the age, education, and MMSE. In the FAB subtest analysis, the performances of PD patients were worse than the healthy participants on similarities, fluency tasks, and Luria's motor series. Persian version of FAB could be used as a reliable scale for the assessment of frontal lobe functions in Iranian patients with PD. Furthermore, normative data provided for the Persian version of this test improve the accuracy and confidence in the clinical application of the FAB.

Personality Traits in Panic Disorder Patients With and Without Comorbidities.

PubMed

Zugliani, Morena M; Martin-Santos, Rocio; Nardi, Antonio Egidio; Freire, Rafael Christophe

2017-11-01

Panic disorder (PD) is often correlated with high neuroticism and low extraversion. This study aims to ascertain whether PD patients differ from healthy controls in regard to personality traits and determine if these traits are correlated with comorbid disorders, anxiety, and depression symptoms. Personality traits of 69 PD patients and 42 controls were compared using the Maudsley Personality Inventory. In PD patients, comorbidities, anxiety, and depression symptoms were also evaluated. PD patients showed higher neuroticism and lower extraversion compared with healthy controls. Patients without comorbidities presented similar results to controls, whereas those with comorbidities presented higher neuroticism and lower extraversion scores. PD per se may be unrelated to deviant personality traits, although comorbidities with major depressive disorder and agoraphobia are probably associated with high neuroticism and low extraversion. These traits show a strong correlation with the accumulation and severity of these disorders.

Risk for Femoral Fractures in Parkinson’s Disease Patients with and without Severe Functional Impairment

PubMed Central

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Background Impaired balance is a major problem in patients with idiopathic Parkinson’s disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Methods Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Results Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28–2.98) than in women (HR = 1.79; 95%-CI: 1.66–1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. Conclusion The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment. PMID:24853110

Competency to consent to medical treatment in cognitively impaired patients with Parkinson's disease.

PubMed

Dymek, M P; Atchison, P; Harrell, L; Marson, D C

2001-01-09

To investigate capacity to consent to medical treatment (competency) in cognitively impaired patients with PD. Although competency has been studied empirically in patients with cortical dementia (AD), no empirical studies have examined competency in patients with PD or other subcortical neurodegenerative disorders. Patients with PD with cognitive impairment (n = 20) and older controls (n = 20) were compared using a standardized competency measure (Capacity to Consent to Treatment Instrument [CCTI]) and neuropsychological test measures. The CCTI tests competency performance and assigns outcomes (capable, marginally capable, incapable) under four different legal standards (LS). Patients with PD performed below controls on the four LS: capacity to evidence a treatment choice (LS1) (p < 0.03), capacity to appreciate consequences of a treatment choice (LS3) (p < 0.03), capacity to provide rational reasons for a treatment choice (LS4) (p < 0.0001), and capacity to understand the treatment situation and choices (LS5) (p < 0.0001). With respect to competency outcomes, patients with PD demonstrated increasing compromise (marginally capable or incapable outcomes) across the four standards: LS1 (25%), LS3 (45%), LS4 (55%), and LS5 (80%). In the PD group, simple measures of executive function (the Executive Interview) and to a lesser extent memory/orientation (Dementia Rating Scale, Memory subscale) were key predictors of competency performance and outcome on the LS. Cognitively impaired patients with PD are likely to have impaired consent capacity, and are at risk of losing competency over the course of their neurodegenerative illness. Patients with PD have particular difficulty meeting more stringent, clinically relevant competency standards that tap reasoning skills and comprehension of treatment information. Executive dysfunction appears to be a primary neurocognitive mechanism for competency loss in PD.

Grade and location of power Doppler are predictive of damage progression in rheumatoid arthritis patients in clinical remission by anti-tumour necrosis factor α.

PubMed

Raffeiner, Bernd; Grisan, Enrico; Botsios, Costantino; Stramare, Roberto; Rizzo, Gaia; Bernardi, Livio; Punzi, Leonardo; Ometto, Francesca; Doria, Andrea

2017-08-01

To investigate power Doppler (PD) signal, grade and location and their association with radiographic progression in RA patients in remission. A prospective observational study was conducted in 125 consecutive RA patients in stable 28-joint DAS (DAS28) remission (⩾6 months) achieved on anti-TNF-α. At baseline, patients in stable remission underwent radiographic and US examination of the wrists and MCP, PIP and MTP joints. Semi-quantitative PD scoring (0-3) was recorded. We scored PD according to two locations: capsular or within synovial tissue without bone contact (location 1) and with bone contact or penetrating bone cortex (location 2). Radiographic progression was evaluated at the 1 year follow-up and defined as a change in van der Heijde-modified total Sharp score >0. Risk ratios (RRs) of radiographic progression according to presence, grade and location of PD were calculated. Four patients were excluded because of missing data. At baseline, 59/121 (48.7%) patients had a PD signal in one or more joints. PD location 2 was found in 74.6% patients (44/59). At the 1 year follow-up, 17/121 patients experienced radiographic progression: all had PD signal in one or more joints at baseline (RR 2.47, P < 0.0001). Radiographic progression was associated with the following baseline US features: PD grade 2 (RR 4.58, P < 0.01), PD grade 3 (RR 3.49, P < 0.05), total PD score ⩾2 (sum of all PD scores) (RR 3.19, P < 0.0001) and PD location 2 (RR 3.49, P < 0.0001). Higher PD grades and PD in contact with/or penetrating bone are associated with radiographic progression in patients in DAS28 remission. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma

PubMed Central

Fang, Xia; Xiu, Bing; Yang, Zhizhang; Qiu, Weizhe; Zhang, Long; Zhang, Suxia; Wu, Yunjin; Zhu, Xuyou; Chen, Xue; Xie, Suhong; Yi, Xianghua; Liang, Aibin; Zeng, Yu

2017-01-01

Abstract Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear. Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan–Meier curves with log rank test, and Cox's proportional hazards regression model. PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients’ gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1+ TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients’ survival time. Besides, PD-1 expression, patients’ age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance. PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients. PMID:28403071

The Association of Musculoskeletal Pain with Bone Mineral Density in Patients with Parkinson's Disease.

PubMed

Choi, Seong-Min; Kim, Byeong C; Jung, Hyun-Jung; Yoon, Geum-Jin; Kang, Kyung Wook; Choi, Kang-Ho; Lee, Seung-Han; Park, Man-Seok; Kim, Myeong-Kyu; Cho, Ki-Hyun

2017-01-01

Pain and osteoporosis are common in Parkinson's disease (PD), and lower bone mineral density (BMD) or osteoporosis may be associated with an increased risk of reporting to have pain in the general population. The aim of this study was to determine whether there is an association between the pain subtypes and the BMD in patients with PD. We included 162 PD patients. Pain was assessed using the patients' descriptions, a structured interview, a detailed neurologic examination, and the Visual Analogue Scale. BMD was measured using dual energy X-ray absorptiometry scans. Of the 162 PD patients, 120 had chronic pain, while 42 reported no pain. The most prevalent type of pain was musculoskeletal, followed by radicular/neuropathic, dystonic, and central. PD patients with musculoskeletal pain had a lower BMD than PD patients without pain. Multivariate regression analysis showed that the low BMD of the lumbar spine, hip, and femoral neck were related to old age, female gender, low MBI, and the presence of musculoskeletal pain. PD patients with musculoskeletal pain have low BMD and are at risk for developing osteoporosis. If a PD patient has musculoskeletal pain and other risk factors related to low BMD, clinicians should consider screening for osteoporosis. © 2017 S. Karger AG, Basel.

Impaired frontal lobe functions in patients with Parkinson's disease and psychosis.

PubMed

Thota, Naveen; Lenka, Abhishek; George, Lija; Hegde, Shantala; Arumugham, Shyam Sundar; Prasad, Shweta; Stezin, Albert; Kamble, Nitish; Yadav, Ravi; Pal, Pramod Kumar

2017-12-01

Patients with Parkinson's disease (PD) may develop several non-motor symptoms (NMS). Psychosis is one of the debilitating NMS of PD. The neurobiology of psychosis is not fully understood. This study aims to compare the frontal lobe functions of PD patients with and without psychosis using the Frontal Assessment Battery (FAB). This study included 69 patients with PD; 34 with psychosis (PD-P) and 35 without psychosis (PD-NP). Mini Mental Status Examination (MMSE) was used to screen for cognitive impairment. Unified Parkinson's disease Rating scale part-III (UPDRS-III) was used to measure the severity and Hoehn and Yahr score (H&Y) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB. The PD-P and PD-NP groups were comparable for age (58.7±8.4 vs 55.7±8.2, p=0.14), age at onset of symptoms (51.4±8.1 vs 50.0±8.8, p=0.48), gender distribution (men: 88%vs 80%, p=0.51), MMSE (28.2±1.9 vs 28.7±1.2 p=0.12), levodopa equivalent dose/day (736.0±376.3 vs 625.2±332.2, p=0.19), UPDRS-III OFF-score (36.7±8.8 vs 35.4±13.2, p=0.64), UPDRS-III ON-score (13.2±5.4 vs 12.4±6.6, p=0.44) and H&Y stage (2.3±0.3 vs 2.3±0.3, p=0.07). PD-P group had lower total FAB score compared to PD-NP group (13.9±2.2 vs 16.5±1.8, p<0.01). On the FAB, PD-P group had lower scores compared to PD-NP in lexical fluency (FAB-2), programming (FAB-3), sensitivity to interference (FAB-4) and inhibitory control (FAB-5). Patients with PD-P had significant frontal lobe dysfunction compared to PD-NP. FAB may be a simple and useful bedside tool to assess frontal dysfunction in patients with PD in a busy neurological set up. Copyright © 2017 Elsevier B.V. All rights reserved.

Driving in Parkinson's disease: mobility, accidents, and sudden onset of sleep at the wheel.

PubMed

Meindorfner, Charlotte; Körner, Yvonne; Möller, Jens Carsten; Stiasny-Kolster, Karin; Oertel, Wolfgang Hermann; Krüger, Hans-Peter

2005-07-01

Only few studies have addressed driving ability in Parkinson's disease (PD) to date. However, studies investigating accident proneness of PD patients are urgently needed in the light of motor disability in PD and--particularly--the report of "sleep attacks" at the wheel. We sent a questionnaire about sudden onset of sleep (SOS) and driving behavior to 12,000 PD patients. Subsequently, of 6,620 complete data sets, 361 patients were interviewed by phone. A total of 82% of those 6,620 patients held a driving license, and 60% of them still participated in traffic. Of the patients holding a driving license, 15% had been involved in and 11% had caused at least one accident during the past 5 years. The risk of causing accidents was significantly increased for patients who felt moderately impaired by PD, had an increased Epworth Sleepiness Scale (ESS) score, and had experienced SOS while driving. Sleep attacks at the wheel usually occurred in easy driving situations and resulted in typical fatigue-related accidents. Those having retired from driving had a more advanced (subjective) disease severity, higher age, more frequently female gender, an increased ESS score, and a longer disease duration. The study revealed SOS and daytime sleepiness as critical factors for traffic safety in addition to motor disabilities of PD patients. The results suggest that real sleep attacks without any prior sleepiness are rare. However, our data underline the importance of mobility for patients and the need for further studies addressing the ability to drive in PD. Copyright 2005 Movement Disorder Society.

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency.

PubMed

Isa, Hasan M; Mohamed, Masooma S; Mohamed, Afaf M; Abdulla, Adel; Abdulla, Fuad

2017-04-01

This study aimed to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among infants with neonatal indirect hyperbilirubinemia (NIH); compare G6PD-deficient and G6PD-normal patients regarding hyperbilirubinemia and need for exchange transfusions (ET); and assess risk factors for ET and kernicterus. This is a case-control retrospective study. Medical records of NIH patients admitted to the Pediatric Department, Salmaniya Medical Complex, Bahrain, between January 2007 and June 2010 were reviewed. Data on sex, age at presentation, hospitalization duration, need for ET, hemoglobin (Hb) level, reticulocyte count, direct Coombs test, serum total and indirect bilirubin levels, thyroid function, blood and urine cultures, G6PD status, and blood groups were collected and compared between the G6PD-deficent and G6PD-normal patients. Of 1,159 NIH patients admitted, 1,129 were included, of whom 646 (57%) were male. Among 1,046 patients tested, 442 (42%) were G6PD deficient, 49 (4%) needed ET, and 11 (1%) had suspected Kernicterus. The G6PD-deficient patients were mainly male ( P <0.0001), and had lower Hb levels ( P <0.0001) and higher maximum bilirubin levels ( P =0.001). More G6PD-deficient patients needed ET ( P <0.0001). G6PD deficiency ( P =0.006), lower Hb level ( P =0.002), lower hematocrit count ( P =0.02), higher bilirubin level ( P <0.0001), higher maximal bilirubin level ( P <0.0001), and positive blood culture result ( P <0.0001) were significant risk factors for ET. Maximal bilirubin level was a significant risk factor for kernicterus ( P =0.021) and independently related to ET ( P =0.03). G6PD deficiency is an important risk factor for severe NIH. In G6PD-deficent neonates, management of NIH should be hastened to avoid irreversible neurological complications.

Offering Patients Therapy Options in Unplanned Start (OPTiONS): Implementation of an educational program is feasible and effective.

PubMed

Machowska, Anna; Alscher, Mark Dominik; Vanga, Satyanarayana Reddy; Koch, Michael; Aarup, Michael; Qureshi, Abdul Rashid; Lindholm, Bengt; Rutherford, Peter

2017-01-13

Patients with unplanned dialysis start (UPS) have worse clinical outcomes than non-UPS patients, and receive peritoneal dialysis (PD) less frequently. In the OPTiONS study of UPS patients, an educational programme (UPS-EP) aiming at improving care of UPS patients by facilitating care pathways and enabling informed choice of dialysis modality was implemented. We here report on impact of UPS-EP on modality choice and clinical outcomes in UPS patients. This non-interventional, prospective, multi-center, observational study included 270 UPS patients from 26 centers in 6 European countries (Austria, Germany, Denmark, France, United Kingdom and Sweden) who prior to inclusion presented acutely, or were being followed by nephrologists but required urgent dialysis commencement by an acutely placed CVC or PD catheter. Effects of UPS-EP on choice and final decision of dialysis therapy and outcomes within 12 months of follow up were analysed. Among 270 UPS patients who had an unplanned start to dialysis, 214 were able to receive and 203 complete UPS-EP while 56 patients - who were older (p = 0.01) and had higher Charlson comorbidity index (CCI; p < 0.01) - did not receive UPS-EP. Among 177 patients who chose dialysis modality after UPS-EP, 103 (58%) chose PD (but only 86% of them received PD) and 74 (42%) chose HD (95% received HD). Logistic regression analysis showed that diabetes 1.88 (1.05 - 3.37) and receiving UPS-EP, OR = 4.74 (CI, 2.05 - 10.98) predicted receipt of PD. Patients choosing PD had higher CCI (p = 0.01), higher prevalence of congestive heart failure (p < 0.01) and myocardial infarction (p = 0.02), and were more likely in-patients (p = 0.02) or referred from primary care (p = 0.02). One year survival did not differ significantly between PD and HD patients. Peritonitis and bacteraemia rates were better than international guideline standards. UPS-EP predicted patient use of PD but 14% of those choosing PD after UPS-EP still did not receive the modality they preferred. Patient survival in patients choosing and/or receiving PD was similar to HD despite age and comorbidity disadvantages of the PD groups.

Parkinson's disease and narcolepsy-like symptoms.

PubMed

Ylikoski, Ari; Martikainen, Kirsti; Sarkanen, Tomi; Partinen, Markku

2015-04-01

Various sleep-related problems, for example, insomnia and symptoms of rapid eye movement behavior disorder (RBD), are common in patients with Parkinson's disease (PD). We studied the prevalence of symptoms of narcolepsy (NARC), hallucinations, and RBD and their association with other symptoms. Altogether, 1447 randomly selected patients with PD, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, RBD, and other issues were included. The response rate was 59.0%; of these patients, 73% had answered to all questions that were used in the analyses (N = 623). The occurrence of suspected narcolepsy (Ullanlinna Narcolepsy Scale ≥ 14 and Epworth Sleepiness Scale ≥ 11) was observed in 9.3% of the subjects (PD with NARC), RBD (REM Sleep Behavior Disorder Screening Questionnaire ≥ 6) in 39.2% of all patients with PD, and in 62.1% of those with PD and NARC. In patients with PD, hallucinations before going to bed in the evening occurred in 5.8%, hypnagogic hallucinations in 4.0%, hallucinations during night 8.3%, and hypnopompic hallucinations in 3.2%. Cataplexy symptoms occurred in 43.1% of subjects with PD and NARC. In a logistic regression analysis, PD with NARC was associated with RBD, all types of hallucinations, daytime sleepiness, fatigue, insomnia, and intense dreaming also when adjusted for age, sex, disease duration, and levodopa. Narcolepsy-like symptoms may be present in patients with PD. Symptoms of RBD were associated with symptoms of narcolepsy including symptoms of cataplexy. Copyright © 2014 Elsevier B.V. All rights reserved.

Blood biomarker for Parkinson disease: peptoids

PubMed Central

Yazdani, Umar; Zaman, Sayed; Hynan, Linda S; Brown, L Steven; Dewey, Richard B; Karp, David; German, Dwight C

2016-01-01

Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r=0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker. PMID:27812535

Periodontal Disease Associated with Aortic Arch Atheroma in Patients with Stroke or Transient Ischemic Attack.

PubMed

Sen, Souvik; Chung, Matthew; Duda, Viktoriya; Giamberardino, Lauren; Hinderliter, Alan; Offenbacher, Steven

2017-10-01

Periodontal disease (PD) is associated with recurrent vascular event in stroke or transient ischemic attack (TIA). In this study, we investigated whether PD is independently associated with aortic arch atheroma (AA). We also explored the relationship PD has with AA plaque thickness and other characteristics associated with atheroembolic risk among patients with stroke or TIA. Finally, we confirmed the association between AA and recurrent vascular event in patients with stroke or TIA. In this prospective longitudinal hospital-based cohort study, PD was assessed in patients with stroke and TIA. Patients with confirmed stroke and TIA (n = 106) were assessed by calibrated dental examiners to determine periodontal status and were followed over a median of 24 months for recurrent vascular events (stroke, myocardial infarction, and death). The extent of AA and other plaque characteristics was assessed by transesophageal echocardiography. Within our patient cohort, 27 of the 106 participants had recurrent vascular events (including 16 with stroke or TIA) over the median of 24-month follow-up. Severe PD was associated with increased AA plaque thickness and calcification. The results suggest that PD may be a risk factor for AA. In this cohort, we confirm the association of severe AA with recurrent vascular events. In patients with stroke or TIA, severe PD is associated with increased AA plaque thickness, a risk factor for recurrent events. Further studies are needed to confirm this finding and to determine whether treatment of PD can reduce the rate of AA plaque progression and recurrent vascular events. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The Clinical Findings Useful for Driving Safety Advice for Parkinson's Disease Patients.

PubMed

Ando, Rina; Iwaki, Hirotaka; Tsujii, Tomoaki; Nagai, Masahiro; Nishikawa, Noriko; Yabe, Hayato; Aiba, Ikuko; Hasegawa, Kazuko; Tsuboi, Yoshio; Aoki, Masashi; Nakashima, Kenji; Nomoto, Masahiro

2018-02-28

Objective We conducted a study to obtain information that could be used to provide Parkinson's disease (PD) patients with appropriate advice on safe driving. Methods Consecutive PD patients who visited our office were studied. Among these patients, those who had experienced driving after being diagnosed with PD were interviewed by neurologists and a trained nurse to investigate their previous car accidents, motor function, cognitive function, sleepiness, levodopa equivalent dose (LED), and emotional dysregulation. The rates of major car accidents before and after the onset of PD were compared. Results Fifteen patients had experienced a major car accident resulting in human injury or serious property damage since the onset of PD. When the rates of major car accidents before and after the onset of PD were compared, the ratio was 4.3 (95% CI 1.9-9.7). The incidence of accidents after the onset of PD was correlated with age, disease duration, LED, the cognitive function (MMSE, MoCA-J), but not the motor symptom score (UPDRS part III at the time of the study). The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) score was also higher in patients with major car accidents. Conclusion The severity of symptoms (Hoehn-Yahr classification), cognitive function, and disease duration were expected to be risk factors for car accidents. However, the motor symptom score (UPDRS part III) was not associated with the incidence of major car accidents. In addition to a low cognitive function and the severity of symptoms, the QUIP score might be an independent factor that can be referenced when advising PD patients to refrain from driving.

PD-L1 expression as poor prognostic factor in patients with non-squamous non-small cell lung cancer.

PubMed

Zhou, Cuiling; Tang, Jianjun; Sun, Huanhuan; Zheng, Xiaobin; Li, Zhanyu; Sun, Tiantian; Li, Jie; Wang, Shuncong; Zhou, Xiuling; Sun, Hongliu; Cheng, Zhibin; Zhang, Hongyu; Ma, Haiqing

2017-08-29

The role of programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), especially according to histologic type, remains controversial. The purpose of this study was to assess PD-L1 expression and its association with overall survival (OS) and clinicopathologic characteristics in NSCLC. Formalin-fixed paraffin-embedded specimens were obtained from 108 patients with surgically resected primary NSCLC. PD-L1 expression was assessed via immunohistochemistry using a histochemistry score system. The relationship between OS or clinicopathologic characteristics and PD-L1 expression was evaluated via the Kaplan-Meier method and Cox proportional hazards model, respectively. Of 108 NSCLC specimens, 44 had high PD-L1 expression, which was highly associated with histologic type ( p = 0.003). Patients without PD-L1 expression had remarkably longer OS than those with PD-L1 expression (median OS: 96 months vs. 33 months, p < 0.001). In the subgroup analysis of non-squamous cell carcinoma, OS was more favorable in those without PD-L1 expression than in those with PD-L1 expression (median OS: 113 months vs. 37 months, p < 0.001). Multivariate analysis revealed that PD-L1 expression (95% confidence interval 1.459-4.520, p < 0.001), male sex and higher tumor-node-metastasis stage were significantly correlated with shorter OS. This study demonstrated that PD-L1 expression is an independent prognostic factor for poor survival in NSCLC patients, especially those with non-squamous NSCLC.

Polyneuropathy in levodopa-treated Parkinson's patients.

PubMed

Szadejko, Karol; Dziewiatowski, Krzysztof; Szabat, Krzysztof; Robowski, Piotr; Schinwelski, Michał; Sitek, Emilia; Sławek, Jarosław

2016-12-15

Recently published studies show that the prevalence of polyneuropathy (PNP) is higher in patients with Parkinson's disease (PD) than in age-matched controls. Its pathogenesis, however is a matter of controversy. The major hypothesis is the toxicity of high concentrations of homocysteine (Hcy) possibly related to levodopa (LD) therapy. The aim of the present study was to determine the prevalence of PNP, independent of other etiologies, and to determine the relationship to demographic and clinical factors in LD-treated Parkinson's patients. A total of 102 patients (51 patients with PD and 51 sex- and age-matched healthy controls) were enrolled in the study. The presence of any risk factors for PNP, ascertained from the history and laboratory tests, was an exclusion criterion. The Toronto Clinical Scoring System (TCSS) was used for clinical assessment of PNP. The objective assessment was based on electroneurography (ENG) studies in which motor nerves (peroneal and tibial nerves) as well as sensory nerves (sural and superficial peroneal nerves) were bilaterally examined. The severity of the disease was determined using the UPDRS scale (Unified Parkinson's Disease Rating Scale) and the Hoehn-Yahr (H-Y) scale. In the PD group, the clinical and neurophysiological indicators of PNP, manifested as a symmetrical and predominantly sensory axonal neuropathy, were more frequent then in the control group and observed in 43.1% vs. 13.7% and 15.7% vs. 2% of subjects respectively. The presence of PNP correlated with age and the severity of PD. Patients with PD and PNP had a higher level of Hcy as compared to PD patients without PNP, however the difference was not statistically significant. The frequency of PNP in PD patients is higher than in controls. The characteristics and discrepancy between the number of patients with clinical and ENG detected PNP may suggest the small fiber neuropathy (SFN) as the dominant form of neuropathy in PD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Visual feedback training using WII Fit improves balance in Parkinson's disease.

PubMed

Zalecki, Tomasz; Gorecka-Mazur, Agnieszka; Pietraszko, Wojciech; Surowka, Artur D; Novak, Pawel; Moskala, Marek; Krygowska-Wajs, Anna

2013-01-01

Postural instability including imbalance is the most disabling long term problem in Parkinson's disease (PD) that does not respond to pharmacotherapy. This study aimed at investigating the effectiveness of a novel visual-feedback training method, using Wii Fit balance board in improving balance in patients with PD. Twenty four patients with moderate PD were included in the study which comprised of a 6-week home-based balance training program using Nintendo Wii Fit and balance board. The PD patients significantly improved their results in Berg Balance Scale, Tinnet's Performance-Oriented Mobility Assessment, Timed Up-and-Go, Sit-to-stand test, 10-Meter Walk test and Activities-specific Balance Confidence scale at the end of the programme. This study suggests that visual feedback training using Wii-Fit with balance board could improve dynamic and functional balance as well as motor disability in PD patients.

Association Between Gastroesophageal Reflux Disease After Pneumatic Balloon Dilatation and Clinical Course in Patients With Achalasia

PubMed Central

Min, Yang Won; Lee, Jin Hee; Min, Byung-Hoon; Lee, Jun Haeng; Kim, Jae J; Rhee, Poong-Lyul

2014-01-01

Background/Aims The occurrence of gastroesophageal reflux disease (GERD) is known to be associated with lower post-treatment lower esophageal sphincter pressure in patients with achalasia. This study aimed to elucidate whether GERD after pneumatic balloon dilatation (PD) has a prognostic role and to investigate how the clinical course of GERD is. Methods A total of 79 consecutive patients who were first diagnosed with primary achalasia and underwent PD as an initial treatment were included in this retrospective study. Single PD was performed using a 3.0 cm balloon. The patients were divided into two groups: 1) who developed GERD after PD (GERD group) and 2) who did not develop GERD after PD (non-GERD group). GERD was defined as pathological acid exposure, reflux esophagitis or typical reflux symptoms. Results Twenty one patients (26.6%) developed GERD after PD during follow-up. There were no significant differences between the two groups in demographic or clinical factors including pre- and post-treatment manometric results. All patients in GERD group were well responsive to maintenance proton pump inhibitor therapy including on demand therapy or did not require maintenance. During a median follow-up of 17.8 months (interquartile range, 7.1–42.7 months), achalasia recurred in 15 patients (19.0%). However, the incidence of recurrence did not differ according to the occurrence of GERD after PD. Conclusions GERD often occurs after even a single PD for achalasia. However, GERD after PD is well responsive to PPI therapy. Our data suggest that GERD after PD during follow-up does not appear to have a prognostic role. PMID:24840373

Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma.

PubMed

Jiang, Yubo; Lo, Anthony W I; Wong, Angela; Chen, Wenfeng; Wang, Yan; Lin, Li; Xu, Jianming

2017-05-02

Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in regulating the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating immune cells (TILs) in the tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Archival formalin-fixed, paraffin-embedded ESCC samples from treatment-naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy were collected between 2004 and 2014. Expression of PD-L1 in ESCC tumor specimens was assessed by immunohistochemistry (IHC), and the degree of TIL infiltration was evaluated by examining hematoxylin and eosin-stained (H&E) specimens. PD-L1+ as defined as ≥1% of tumor cell membranes showing ≥1+ intensity. In 428 patients, specimens from 341 (79.7%) were PD-L1+. In the definitive treatment group (patients who received curative esophagectomy or definitive [chemo-]radiation therapy), PD-L1 positivity was associated with a significantly shorter DFS and OS. In the palliative chemotherapy group exhibited, neither PFS nor OS correlated significantly with PD-L1 expression. PD-L1 expression was positively associated with TIL density. In 17 paired tumor tissues collected before and after treatment, an increase in PD-L1 expression was associated with disease progression, whereas a decrease in PD-L1 expression was associated with response to chemotherapy or disease control. So, PD-L1 expression was associated with a significantly worse prognosis in patients with ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients.

The intratumoral balance between metabolic and immunologic gene expression is associated with anti-PD-1 response in patients with renal cell carcinoma

PubMed Central

Ascierto, Maria Libera; McMiller, Tracee L.; Berger, Alan E.; Danilova, Ludmila; Anders, Robert A.; Netto, George J.; Xu, Haiying; Pritchard, Theresa S.; Fan, Jinshui; Cheadle, Chris; Cope, Leslie; Drake, Charles G.; Pardoll, Drew M.; Taube, Janis M.; Topalian, Suzanne L.

2016-01-01

Pretreatment tumor PD-L1 expression correlates with response to anti-PD-1/PD-L1 therapies. Yet, most patients with PD-L1+ tumors do not respond to treatment. The current study was undertaken to investigate mechanisms underlying the failure of PD-1–targeted therapies in patients with advanced renal cell carcinoma (RCC) whose tumors express PD-L1. Formalin-fixed, paraffin-embedded (FFPE) pretreatment tumor biopsies expressing PD-L1 were derived from 13 RCC patients. RNA was isolated from PD-L1+ regions and subjected to whole genome microarray and multiplex quantitative (q)RT-PCR gene expression analysis. A balance between gene expression profiles reflecting metabolic pathways and immune functions was associated with clinical outcomes following anti-PD-1 therapy. In particular, the expression of genes involved in metabolic and solute transport functions such as UGT1A family members, also found in kidney cancer cell lines, was associated with treatment failure in patients with PD-L1+ RCC. Conversely, tumors from responding patients overexpressed immune markers such as BACH2, a regulator of CD4+ T cell differentiation, and CCL3, involved in leukocyte migration. These findings suggest that tumor cell–intrinsic metabolic factors may contribute to treatment resistance in RCC, thus serving as predictive markers for treatment outcomes and potential new targets for combination therapy regimens with anti-PD-1. PMID:27491898

Risk factors of severe peritoneal sclerosis in chronic peritoneal dialysis patients.

PubMed

Alatab, Sudabeh; Najafi, Iraj; Pourmand, Gholamreza; Hosseini, Mostafa; Shekarchian, Soroosh

2017-11-01

Peritoneal dialysis (PD) offers the healthiest way for starting renal replacement therapy (RRT) in End Stage Renal Disease patients, however exposes long-term PD patients to a dangerous complication named encapsulating peritoneal sclerosis (EPS). In this study, we searched for possible risk factors of EPS. Data were collected from two PD centers covering period 1995-2012 and comprised 464 patients. Control group defined as PD patients stayed on PD >42 month (n = 122), and case group was 12 confirmed EPS patients. Associations were analyzed using linear regression analysis. Prevalence and incidence of EPS were 2.59% and 8.9% with an incidence of 0.7% patient-years, respectively. The age at start of PD in EPS patients (32.75 ± 10.8 year) was significantly lower compared with control group (49.61 ± 16.18 year, p = .0001). The mean duration of PD in EPS and control group were 2494.4 ± 940.9 and 1890.2 ± 598.8 days (p = .002). Control group had 145 episodes of peritonitis during total duration of 7686 patient months (peritonitis rate of 1/53). This was 1/26 with a total 38 episodes of peritonitis during the total duration of 997 patient months (p = .01) for EPS group. In regression analysis, PD duration, age at PD start and duration of Ultrafiltration failure (UFF) were associated with EPS. Longer time being on PD, younger age, and higher UFF duration were the risk factors for EPS development.

Depression and care-dependency in Parkinson's disease: results from a nationwide study of 1449 outpatients.

PubMed

Riedel, O; Dodel, R; Deuschl, G; Klotsche, J; Förstl, H; Heuser, I; Oertel, W; Reichmann, H; Riederer, P; Trenkwalder, C; Wittchen, H-U

2012-06-01

Parkinson's disease (PD) is frequently compounded by neuropsychiatric complications, increasing disability. The combined effect of motor and mental status on care-dependency in PD outpatients is not well characterized. We conducted a cross-sectional study of 1449 PD outpatients. The assessment comprised the Montgomery-Asberg Depression Rating Scale (MADRS) and the diagnostic criteria for dementia. PD severity and treatment complications were rated using Hoehn and Yahr staging and the Unified Parkinson's Disease Rating Scale (UPDRS) IV. The acknowledged level of care-dependency was documented. Care-dependency was present in 18.3% of all patients. A total of 13.9% had dementia, 18.8% had depression, and 14.3% had both. Regression analyses revealed increasing effects of age, PD duration, and PD severity on care-dependency in all three mental-disorder subgroups with the strongest effects in patients with depression only. Depressed patients with antidepressive treatment still had significantly higher PD severity, higher MADRS and UPDRS-IV scores but were not more likely to be care-dependent than non-depressed patients. Older age, longer duration and increased severity of PD contribute to care-dependency in patients with untreated depression. Treatment of depression is associated with lower rates of care-dependency. Copyright © 2011 Elsevier Ltd. All rights reserved.

Interactions between EGFR and PD-1/PD-L1 pathway: Implications for treatment of NSCLC.

PubMed

Li, Xue; Lian, Zhen; Wang, Shuai; Xing, Ligang; Yu, Jinming

2018-04-01

Immune checkpoint inhibitors targeting the programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway displayed striking and durable clinical responses in patients with non-small-cell lung cancer (NSCLC). However, it is still undefined about the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients with EGFR activating mutations. Preclinical studies indicate the immune modulatory effect of EGFR signaling by regulating expression of MHC I/II and PD-L1 on tumor cells and activity of lymphocytes. Thus, it might be practicable for the use of PD-1/PD-L1 inhibitors as monotherapy or combined with EGFR-TKIs in patients with EGFR activating mutations. In this review, we discussed the regulation effect of EGFR signaling on PD-1/PD-L1 pathway and the potential mechanisms behind combing EGFR-TKIs with PD-1/PD-L1 inhibitors. We also reviewed current available data on PD-1/PD-L1 inhibitors as monotherapy or combined with EGFR-TKIs in NSCLC with EGFR activating mutations, and explored possible factors influence its efficacy, which would be important considerations for future clinical trial designs. Copyright © 2018 Elsevier B.V. All rights reserved.

Gene Expression Differences in Peripheral Blood of Parkinson’s Disease Patients with Distinct Progression Profiles

PubMed Central

Soreq, Lilach; Lobo, Patrícia P.; Mestre, Tiago; Coelho, Miguel; Rosa, Mário M.; Gonçalves, Nilza; Wales, Pauline; Mendes, Tiago; Gerhardt, Ellen; Fahlbusch, Christiane; Bonifati, Vincenzo; Bonin, Michael; Miltenberger-Miltényi, Gabriel; Borovecki, Fran; Soreq, Hermona; Ferreira, Joaquim J.; F. Outeiro, Tiago

2016-01-01

The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson’s disease (PD) progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression analysis in aiding patient stratification and therapeutic intervention. PMID:27322389

Endotherapy is effective for pancreatic ductal disruption: A dual center experience.

PubMed

Das, Rohit; Papachristou, Georgios I; Slivka, Adam; Easler, Jeffrey J; Chennat, Jennifer; Malin, Jessica; Herman, Justin B; Laique, Sobia N; Hayat, Umar; Ooi, Yinn Shaung; Rabinovitz, Mordechai; Yadav, Dhiraj; Siddiqui, Ali A

2016-01-01

Pancreatic duct (PD) disruptions occur as a result of different etiologies and can be managed medically, endoscopically, or surgically. The aim of this study was to provide an evaluation on the efficacy of endotherapy for treatment of PD disruption in a large cohort of patients and identify factors that predict successful treatment outcome. We retrospectively evaluated consecutive patients who underwent endoscopic retrograde pancreatography (ERP) for transpapillary pancreatic stent placement for PD disruption from 2008 to 2013 at two tertiary referral institutions. PD disruption was defined as extravasation of contrast from the pancreatic duct as seen on ERP. Therapeutic success was defined by resolution of PD leak on ERP, clinical, and/or imaging evaluation. We evaluated 107 patients (58% male, mean age 53 years) with PD disruption. Etiologies of PD disruption were acute pancreatitis (36%), post-operative (31%), chronic pancreatitis (29%), and trauma (4%). PD disruption was successfully bridged by a stent in 45 (44%) patients. Two patients developed post-sphincterotomy bleeding, two had stent migration, and two patients died as a result of post-ERP related complications. Placement of a PD stent was successful in 103/107 (96%) patients. Therapeutic success was achieved in 80/107 (75%) patients. Non-acute pancreatitis etiologies and absence of complete duct disruption were independent predictors of therapeutic success. Endoscopic therapy using a transpapillary stent for PD disruption is safe and effective. Absence of complete duct disruption and non-AP etiologies determine a favorable endoscopic outcome. Published by Elsevier India Pvt Ltd.

Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease.

PubMed

Lim, S W; Zhao, Y; Chua, E; Law, H Y; Yuen, Y; Pavanni, R; Wong, M C; Ng, I S; Yoon, C S; Puong, K Y; Lim, S H; Tan, E K

2006-07-31

Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.

Functional brain imaging of cognitive dysfunction in Parkinson's disease.

PubMed

Hirano, Shigeki; Shinotoh, Hitoshi; Eidelberg, David

2012-10-01

Multiple factors are involved in the development of cognitive impairment in Parkinson's disease (PD) and related disorders. Notably, several underlying factors, such as monoaminergic dysfunction, Lewy body pathology, Alzheimer disease-like pathology and cerebrovascular disease are implied in the PD pathophysiology of cognitive impairment. The mesocortical dopaminergic system is associated with executive functions which are frequently affected in PD and are influenced by local levodopa concentration, dopamine metabolism and baseline performance status. The ventral striatum and frontal cortex are associated with impulse control disorders reported in PD patients treated with dopamine replacement therapy. Cholinergic impairment in PD plays a cardinal role in the development of dementia. Acetylcholinesterase positron emission tomography demonstrates that posterior brain areas are related to cognitive decline in PD patients. Amyloid radiotracer illustrates that patients with PD with severe cognitive impairment were prone to accompanied cortical amyloid deposition. Metabolism/perfusion change associated with cognitive impairment in PD, so-called PD related cognitive pattern, is characterised by reduced frontoparietal activity and is an effective way to differentiate and monitor cognitive function of individual PD patients. Cognitive impairment in PD cannot be explained by a single mechanism and is entangled by multiple factors. Imaging studies can unravel each pathological domain, further shed light on the interrelation between different pathomechanisms, not only in PD but also in other dementia related disorders, and thereby integrate its interpretation to apply to therapeutics in individual patients.

Abnormal ventral tegmental area-anterior cingulate cortex connectivity in Parkinson's disease with depression.

PubMed

Wei, Luqing; Hu, Xiao; Yuan, Yonggui; Liu, Weiguo; Chen, Hong

2018-07-16

Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease. The present study used resting-state fMRI and seed-based functional connectivity of putative dopaminergic midbrain regions (i.e., substantia nigra (SN) and ventral tegmental area (VTA)) to investigate the circuit-related abnormalities in PD with depression. The results showed that depressed PD (DPD) patients relative to healthy controls (HC) and non-depressed PD (NDPD) patients had increased functional connectivity between VTA and anterior cingulate cortex (ACC), demonstrating that dysfunctional mesocorticolimbic dopaminergic neurotransmission may be associated with depression in PD. Compared with HC, DPD and NDPD patients showed increased functional connectivity from SN to sensorimotor cortex, validating that alterations in the nigrostriatal circuitry could be responsible for cardinal motor features in PD. In addition, aberrant connectivity between VTA and ACC was correlated with the severity of depression in PD patients, further supporting that abnormal mesocorticolimbic system may account for depressive symptoms in PD. These results have provided potential circuit-level biomarkers of depression in PD, and suggested that resting state functional connectivity of midbrain dopaminergic nuclei may be useful for understanding the underlying pathology in PD with depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Outcomes of a Peritoneal Dialysis Program in Remote Communities Within Colombia

PubMed Central

Sanabria, Mauricio; Devia, Martha; Hernández, Gilma; Astudillo, Kindar; Trillos, Carlos; Uribe, Mauricio; Latorre, Catalina; Bernal, Astrid; Rivera, Angela

2015-01-01

♦ Background and Objective: Colombia is a country of diverse geographic regions, some with mountainous terrain that can make access to urban areas difficult for individuals who live in remote areas. In 2005, a program was initiated to establish remote peritoneal dialysis (PD) centers in Colombia to improve access to PD for patients with end-stage renal disease who face geographic or financial access barriers. ♦ Patients and Methods: The present study was a multi-center cohort observational study of prevalent home PD patients who were at least 18 years of age and were being managed by one of nine established remote PD centers in Colombia over a 2-year period. Data were collected from clinical records, databases, and patient interviews. Patient survival, incidence of peritonitis, and rate of withdrawal from PD therapy were assessed. ♦ Results: A total of 345 patients were eligible for the study. The majority (87.8%) of patients lived on one to two times a minimum monthly salary (equivalent to US$243 – US$486). On average, patients traveled 1.2 hours and 4.3 hours from their home to their remote PD center or an urban reference renal clinic, respectively. The incidence rate of peritonitis was 2.54 episodes per 100 patient-months of therapy. A bivariate analysis showed a significantly higher risk of peritonitis in patients who were living on less than one times a monthly minimum salary (p < 0.05) or who had a dirt, cement, or unfinished wood floor (p < 0.05). The 1-year and 2-year patient survival rates were 92.44% and 81.55%, respectively. The 1-year and 2-year technique survival rates were 97.27% and 89.78%, respectively. ♦ Conclusions: With the support of remote PD centers that mitigate geographic and financial barriers to healthcare, home PD therapy is a safe and appropriate treatment option for patients who live in remote areas in Colombia. PMID:24497583

Prevalence of Sarcopenia and Dynapenia and Their Determinants in Iranian Peritoneal Dialysis Patients.

PubMed

As'habi, Atefeh; Najafi, Iraj; Tabibi, Hadi; Hedayati, Mehdi

2018-01-01

Uremic sarcopenia and dynapenia are prevalent in chronic kidney disease patients, including dialysis patients. The present study was designed to determine the prevalence of sarcopenia and dynapenia and their determinants in peritoneal dialysis (PD) patients in Tehran, Iran. All eligible PD patients at the peritoneal dialysis centers of Tehran were included in this cross-sectional study. Skeletal muscle mass and muscle strength were assessed using bioelectrical impedance analysis and hand grip strength, respectively. Physical performance was determined by a 4-m walk gait speed test. The prevalence rates of dynapenia and sarcopenia were 43.0% and 11.5% in the PD patients, respectively. There were significant associations between the prevalence of dynapenia and the age of patients (P = .03), physical activity level (P = .04), and the presence of diabetes mellitus (P = .005). In addition, a significant association was found between the prevalence of sarcopenia and sex (P = .009). This study indicates that uremic sarcopenia and dynapenia are prevalent in PD patients in Tehran, Iran. These conditions may contribute to physical disability, decreased the quality of life, increased morbidity, and a high mortality rate. Therefore, prevention and treatment of uremic sarcopenia and dynapenia are necessary for Iranian PD patients.

Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

PubMed

Forkmann, Katarina; Grashorn, Wiebke; Schmidt, Katharina; Fründt, Odette; Buhmann, Carsten; Bingel, Ulrike

2017-08-01

Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

Is Peritonitis Risk Increased in Elderly Patients on Peritoneal Dialysis? Report from the French Language Peritoneal Dialysis Registry (RDPLF).

PubMed

Duquennoy, Simon; Béchade, Clémence; Verger, Christian; Ficheux, Maxence; Ryckelynck, Jean-Philippe; Lobbedez, Thierry

2016-01-01

♦ This study was carried out to examine whether or not elderly patients on peritoneal dialysis (PD) had an increased risk of peritonitis. ♦ This was a retrospective cohort study based on data from the French Language Peritoneal Dialysis Registry. We analyzed 8,396 incident patients starting PD between January 2003 and December 2010. The end of the observation period was 31 December 2012. Patients were separated into 2 age groups: up to 75 and over of 75 years old. ♦ Among 8,396 patients starting dialysis there were 3,173 patients older than 75. When using a Cox model, no association was found between age greater than 75 years and increased risk of peritonitis (hazard ratio [HR]: 0.97 [0.88 - 1.07]). Diabetes (HR: 1.14 [1.01 - 1.28] and continuous ambulatory PD (HR: 1.13 [1.04 - 1.23]) were significantly associated with a higher risk of peritoneal infection whereas nurse-assisted PD was associated with a lower risk of peritonitis (HR: 0.85 [0.78 - 0.94]. In the analysis restricted to the 3,840 self-care PD patients, there was no association between age older than 75 years and risk of peritonitis. ♦ The risk of peritonitis is not increased in elderly patients on PD in a country where assisted PD is available. Copyright © 2016 International Society for Peritoneal Dialysis.

A discrete event simulation model to evaluate the use of community services in the treatment of patients with Parkinson's disease in the United Kingdom.

PubMed

Lebcir, Reda; Demir, Eren; Ahmad, Raheelah; Vasilakis, Christos; Southern, David

2017-01-18

The number of people affected by Parkinson's disease (PD) is increasing in the United Kingdom driven by population ageing. The treatment of the disease is complex, resource intensive and currently there is no known cure to PD. The National Health Service (NHS), the public organisation delivering healthcare in the UK, is under financial pressures. There is a need to find innovative ways to improve the operational and financial performance of treating PD patients. The use of community services is a new and promising way of providing treatment and care to PD patients at reduced cost than hospital care. The aim of this study is to evaluate the potential operational and financial benefits, which could be achieved through increased integration of community services in the delivery of treatment and care to PD patients in the UK without compromising care quality. A Discrete Event Simulation model was developed to represent the PD care structure including patients' pathways, treatment modes, and the mix of resources required to treat PD patients. The model was parametrised with data from a large NHS Trust in the UK and validated using information from the same trust. Four possible scenarios involving increased use of community services were simulated on the model. Shifting more patients with PD from hospital treatment to community services will reduce the number of visits of PD patients to hospitals by about 25% and the number of PD doctors and nurses required to treat these patients by around 32%. Hospital based treatment costs overall should decrease by 26% leading to overall savings of 10% in the total cost of treating PD patients. The simulation model was useful in predicting the effects of increased use of community services on the performance of PD care delivery. Treatment policies need to reflect upon and formalise the use of community services and integrate these better in PD care. The advantages of community services need to be effectively shared with PD patients and carers to help inform management choices and care plans.

Central cholinergic dysfunction could be associated with oropharyngeal dysphagia in early Parkinson's disease.

PubMed

Lee, Kyung Duck; Koo, Jung Hoi; Song, Sun Hong; Jo, Kwang Deog; Lee, Moon Kyu; Jang, Wooyoung

2015-11-01

Dysphagia is an important issue in the prognosis of Parkinson's disease (PD). Although several studies have reported that oropharyngeal dysphagia may be associated with cognitive dysfunction, the exact relationship between cortical function and swallowing function in PD patients is unclear. Therefore, we investigated the association between an electrophysiological marker of central cholinergic function, which reflected cognitive function, and swallowing function, as measured by videofluoroscopic studies (VFSS). We enrolled 29 early PD patients. Using the Swallowing Disturbance Questionnaire (SDQ), we divided the enrolled patients into two groups: PD with dysphagia and PD without dysphagia. The videofluoroscopic dysphagia scale (VDS) was applied to explore the nature of the dysphagia. To assess central cholinergic dysfunction, short latency afferent inhibition (SAI) was evaluated. We analyzed the relationship between central cholinergic dysfunction and oropharyngeal dysphagia and investigated the characteristics of the dysphagia. The SAI values were significantly different between the two groups. The comparison of each VFSS component between the PD with dysphagia group and the PD without dysphagia group showed statistical significance for most of the oral phase components and for a single pharyngeal phase component. The total score on the VDS was higher in the PD with dysphagia group than in the PD without dysphagia group. The Mini-Mental State Examination and SAI values showed significant correlations with the total score of the oral phase components. According to binary logistic regression analysis, SAI value independently contributed to the presence of dysphagia in PD patients. Our findings suggest that cholinergic dysfunction is associated with dysphagia in early PD and that an abnormal SAI value is a good biomarker for predicting the risk of dysphagia in PD patients.

Impulse control disorders in Parkinson's disease: the role of personality and cognitive status.

PubMed

Poletti, Michele; Bonuccelli, Ubaldo

2012-11-01

This study reviews empirical findings on two debated issues related to the phenomenon of impulse control disorders (ICD) in patients with Parkinson's disease (PD) treated with dopamine agonists: the role of "premorbid" or "baseline" personality traits and the role of cognitive status. A review of both these issues may help clinicians to understand why only some PD patients, when treated with dopamine agonists, develop an ICD: besides the treatment, which other neuropsychiatric characteristics represent a risk factor to develop an ICD? A literature review was performed on studies of ICD in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in January 2011. In the general population, impulsivity, depression and difficulties with executive functions, especially of inhibitory control, are factors associated with ICD development. As regards cognitive functions, PD patients present executive difficulties, and patients with ICD present more difficulties in comparison to patients without ICD. As regards personality characteristics, PD patients present a trait of negative affect, which could predispose them to affective disorders and could represent an affective risk factor for the development of ICD; as regards impulsivity, preliminary findings support the hypothesis that premorbid "baseline" levels may moderate the decrease of impulsivity because of the progressive dopaminergic deficit in PD patients and therefore also moderate the development of ICD. Longitudinal psychometric and cognitive studies, following PD patients since the clinical diagnosis and during dopaminergic treatment, are needed to confirm the role of personality traits and cognitive status on ICD development in this clinical population.

Risk and Prognosis of Bacteremia and Fungemia Among Peritoneal Dialysis Patients: A Population-Based Cohort Study.

PubMed

Dalgaard, Lars Skov; Nørgaard, Mette; Povlsen, Johan Vestergaard; Jespersen, Bente; Jensen-Fangel, Søren; Ellermann-Eriksen, Svend; Østergaard, Lars; Schønheyder, Henrik Carl; Søgaard, Ole Schmeltz

♦ BACKGROUND: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). ♦ OBJECTIVE: The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. ♦ METHODS: Design: Observational cohort study. Central and North Denmark regions. patients who initiated PD during 1995 - 2010. For each patient we sampled up to 10 controls from the general population matched on age, sex, and municipality. ♦ MAIN OUTCOME: Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. ♦ RESULTS: Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 - 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 - 0.5) per 100 PYFU in population controls (IRR = 10.4; 95% CI, 8.1 - 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 - 31.0) and 20.7% (95% CI, 16.3 - 25.9) among PD patients and population controls, respectively. ♦ CONCLUSIONS: Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts. Copyright © 2016 International Society for Peritoneal Dialysis.

Compliance in peritoneal dialysis: a qualitative study of renal nurses.

PubMed

McCarthy, Alexandra; Cook, Peta S; Fairweather, Carrie; Shaban, Ramon; Martin-McDonald, Kristine

2009-06-01

End-stage renal failure is a life-threatening condition, often treated with home-based peritoneal dialysis (PD). PD is a demanding regimen, and the patients who practise it must make numerous lifestyle changes and learn complicated biomedical techniques. In our experience, the renal nurses who provide most PD education frequently express concerns that patient compliance with their teaching is poor. These concerns are mirrored in the renal literature. It has been argued that the perceived failure of health professionals to improve compliance rates with PD regimens is because 'compliance' itself has never been adequately conceptualized or defined; thus, it is difficult to operationalize and quantify. This paper examines how a group of Australian renal nurses construct patient compliance with PD therapy. These empirical data illuminate how PD compliance operates in one practice setting; how it is characterized by multiple and often competing energies; and how ultimately it might be pointless to try to tame 'compliance' through rigid definitions and measurement, or to rigidly enforce it in PD patients. The energies involved are too fractious and might be better spent, as many of the more experienced nurses in this study argue, in augmenting the energies that do work well together to improve patient outcomes.

Effects of training and weight support on muscle activation in Parkinson's disease.

PubMed

Rose, Martin H; Løkkegaard, Annemette; Sonne-Holm, Stig; Jensen, Bente R

2013-12-01

The aim of this study was to investigate the effect of high-intensity locomotor training on knee extensor and flexor muscle activation and adaptability to increased body-weight (BW) support during walking in patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD and eight healthy participants were included. The PD patients completed an 8-week training program on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles activation during steady treadmill walking (3 km/h) were measured before, at the mid-point, and after training. Increasing BW support decreased knee extensor muscle activation (normalization) and increased knee flexor muscle activation (abnormal) in PD patients when compared to healthy participants. Training improved flexor peak muscle activation adaptability to increased (BW) support during walking in PD patients. During walking without BW support shorter knee extensor muscle off-activation time and increased relative peak muscle activation was observed in PD patients and did not improve with 8 weeks of training. In conclusion, patients with PD walked with excessive activation of the knee extensor and flexor muscles when compared to healthy participants. Specialized locomotor training may facilitate adaptive processes related to motor control of walking in PD patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Socioeconomic status in relation to Parkinson's disease risk and mortality: A population-based prospective study.

PubMed

Yang, Fei; Johansson, Anna L V; Pedersen, Nancy L; Fang, Fang; Gatz, Margaret; Wirdefeldt, Karin

2016-07-01

Little is known about the role of socioeconomic status in relation to Parkinson's disease (PD) risk, and no study has investigated whether the impact of socioeconomic status on all-cause mortality differs between individuals with and without PD.In this population-based prospective study, over 4.6 million Swedish inhabitants who participated in the Swedish census in 1980 were followed from 1981 to 2010. The incidence rate of PD and incidence rate ratio were estimated for the association between socioeconomic status and PD risk. Age-standardized mortality rate and hazard ratio (HR) were estimated for the association between socioeconomic status and all-cause mortality for individuals with and without PD.During follow-up, 66,332 incident PD cases at a mean age of 76.0 years were recorded. Compared to individuals with the highest socioeconomic status (high nonmanual workers), all other socioeconomic groups (manual or nonmanual and self-employed workers) had a lower PD risk. All-cause mortality rates were higher in individuals with lower socioeconomic status compared with high nonmanual workers, but relative risks for all-cause mortality were lower in PD patients than in non-PD individuals (e.g., for low manual workers, HR: 1.12, 95% confidence interval [CI]: 1.09-1.15 for PD patients; HR: 1.36, 95% CI: 1.35-1.36 for non-PD individuals).Individuals with lower socioeconomic status had a lower PD incidence compared to the highest socioeconomic group. Lower socioeconomic status was associated with higher all-cause mortality among individuals with and without PD, but such impact was weaker among PD patients.

A Cost Evaluation of Peritoneal Dialysis and Hemodialysis in the Treatment of End-Stage Renal Disease in São Paulo, Brazil

PubMed Central

de Abreu, Mirhelen Mendes; Walker, David R.; Sesso, Ricardo C.; Ferraz, Marcos B.

2013-01-01

♦ Objective: Conventional hemodialysis (HD) predominates over peritoneal dialysis (PD) around the world. Prospective and comparative studies comparing the costs of these modalities are scarce. In the present prospective assessment, we describe the resources used and total patient costs for both HD and PD. ♦ Methodology: We assessed 249 patients on HD and 228 on PD. All patients were 18 years of age or older and on stable dialysis. The information was collected at three points over 1 year, using standard questionnaires. The sources for costs were the Brazilian public and private health care systems. Societal perspective was considered. ♦ Statistical Analysis: Core trends and dispersions were measured. Regression models assessed the impact of modality on the average total cost per patient per year. ♦ Results: Of the 249 HD patients and 228 PD dialysis patients, 189 (74%) and 160 (70%) respectively completed follow-up. The mean age for women was 55.8 years; for men, it was 59.8 years (p = 0.001). The average total cost per patient-year was US$28 570 for HD and US$27 158 for PD. By category, the costs consisted of direct medical-hospital costs (82.3% for HD, 86.5% for PD), direct nonmedical costs (5.3% for HD, 3.7% for PD), and indirect costs (12.4% for HD, 9.8% for PD). Overall costs were less for PD patients than for their HD counterparts (p = 0.025). ♦ Conclusions: Maintenance dialysis represented the most important source of costs for both modalities; loss of productivity incurred significant costs. Future studies should contemplate the social consequences arising from each modality. PMID:23209041

Protein intake, nitrogen balance and nutritional status in patients with Parkinson's disease; time for a change?

PubMed

Zilli Canedo Silva, Maryanne; Carol Fritzen, Natali; de Oliveira, Marlon; Paes da Silva, Michel; Rasmussen Petterle, Ricardo; Teive, Hélio Afonso; de Mesquita Barros Almeida Leite, Christiane; Rabito, Estela Iraci; Madalozzo Schieferdecker, Maria Eliana; Carvalho, Mauricio

2015-06-01

To evaluate protein intake, nitrogen balance and nutritional status of clinically stable patients with Parkinson's disease (PD). A cross-sectional study of PD patients Hoehn-Yahr scale stage 1-3 and subjects with no neurologic disease (controls) matched for age and gender. All participants underwent a diet history interview, anthropometric measurements, bioelectrical impedance and food record over three non-consecutive days, including a weekend. A 24-hour urine collection and fasting venous blood sampling were collected from the participants for evaluation of creatinine clearance, creatinine height index and the nitrogen balance. The mean age of PD patients was 58.9 ± 12.8 year compared to 54.7 ± 12.6 year of the controls, P = 0.34. One third of PD group had symptoms of dysphagia and ingested less water and fibers when compared to controls. Calf circumference was small in PD group (35.5 ± 2.8 vs. 38.4 ± 3.5 cm, P = 0.012). Intake of nitrogen was significantly lower and nitrogen balance was negative in PD patients (-1.8 ± 3.9 vs. 1.1 ± 4.2 controls, P = 0.06). The antioxidants folate and vitamin E were consumed in small amounts in both groups, although significantly less in PD patients (P = 0.04 and 0.03, respectively). Daily intakes of protein of approximately 1.1 g/kg by clinically stable PD patients may not be enough to ensure a neutral calorie-nitrogen balance and muscle tissue conservation. Larger studies are necessary to provide a more comprehensive picture of PD patients' metabolic status. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

The Evolution of REM Sleep Behavior Disorder in Early Parkinson Disease

PubMed Central

Sixel-Döring, Friederike; Zimmermann, Johannes; Wegener, Andrea; Mollenhauer, Brit; Trenkwalder, Claudia

2016-01-01

Study Objectives: To investigate the development of REM sleep behavior disorder (RBD) and REM sleep behavioral events (RBE) not yet fulfilling diagnostic criteria for RBD as markers for neurodegeneration in a cohort of Parkinson disease (PD) patients between their de novo baseline assessment and two-year follow-up in comparison to healthy controls (HC). Methods: Clinically confirmed PD patients and HC with video-supported polysomnography (vPSG) data at baseline were re-investigated after two years. Diagnostic scoring for RBE and RBD was performed in both groups and related to baseline findings. Results: One hundred thirteen PD patients and 102 healthy controls (HC) were included in the study. Within two years, the overall occurrence of behaviors during REM sleep in PD patients increased from 50% to 63% (P = 0.02). RBD increased from 25% to 43% (P < 0.001). Eleven of 29 (38%) RBE positive PD patients and 10/56 (18%) patients with normal REM sleep at baseline converted to RBD. In HC, the occurrence of any REM behavior increased from 17% to 20% (n.s.). RBD increased from 2% to 4% (n.s.). One of 15 (7%) RBE positive HC and 1/85 (1%) HC with normal REM at baseline converted to RBD. Conclusions: RBD increased significantly in PD patients from the de novo state to two-year follow-up. We propose RBE being named “prodromal RBD” as it may follow a continuous evolution in PD possibly similar to the spreading of Lewy bodies in PD patients. RBD itself was shown as a robust and stable marker of early PD. Citation: Sixel-Döring F, Zimmermann J, Wegener A, Mollenhauer B, Trenkwalder C. The evolution of REM sleep behavior disorder in early Parkinson disease. SLEEP 2016;39(9):1737–1742. PMID:27306265

Neuropsychiatric symptoms and caregiver's burden in Parkinson's disease.

PubMed

Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Forjaz, Maria João; Frades-Payo, Belén; Agüera-Ortiz, Luis; Weintraub, Daniel; Riesco, Ana; Kurtis, Monica M; Chaudhuri, Kallol Ray

2015-06-01

In Parkinson's disease (PD), neuropsychiatric symptoms (NPS) can be particularly burdensome for caregivers. The main goal of this study was to assess the impact of NPS, assessed by means of a new specific scale, on caregiver burden. A sample of 584 pairs of PD patients and their primary caregivers was studied. Patients' NPS were measured with the Scale for Evaluation of Neuropsychiatric Disorders in PD (SEND-PD), and the Zarit Caregiver Burden Inventory was used to quantify caregiver burden. Three linear regression models were built to check factors associated with caregiver burden, one for the total sample and two for subgroups stratified by the presence of dementia. The most frequent NPS were depression (in 66% of the sample), anxiety (65%) and mental fatigue (57%). Patients with dementia (n = 94; 16% of sample) consistently presented more NPS than patients without dementia (p < 0.001). On linear regression models, the main determinants of caregiver burden (for the total sample and the sample of patients without dementia) were SEND-PD dimensions mood/apathy and psychosis, PD-related disability and disease duration. For patients with dementia, the only significant caregiver burden determinants were SEND-PD psychosis and mood/apathy subscale scores. NPS in PD are highly associated with and are determinants of caregiver burden, and are more prevalent and burdensome in patients with dementia. Detailed assessment and specific interventions aimed at NPS could alleviate caregiver burden. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.

PubMed

Fernández-Santiago, Rubén; Carballo-Carbajal, Iria; Castellano, Giancarlo; Torrent, Roger; Richaud, Yvonne; Sánchez-Danés, Adriana; Vilarrasa-Blasi, Roser; Sánchez-Pla, Alex; Mosquera, José Luis; Soriano, Jordi; López-Barneo, José; Canals, Josep M; Alberch, Jordi; Raya, Ángel; Vila, Miquel; Consiglio, Antonella; Martín-Subero, José I; Ezquerra, Mario; Tolosa, Eduardo

2015-12-01

The epigenomic landscape of Parkinson's disease (PD) remains unknown. We performed a genomewide DNA methylation and a transcriptome studies in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) generated by cell reprogramming of somatic skin cells from patients with monogenic LRRK2-associated PD (L2PD) or sporadic PD (sPD), and healthy subjects. We observed extensive DNA methylation changes in PD DAn, and of RNA expression, which were common in L2PD and sPD. No significant methylation differences were present in parental skin cells, undifferentiated iPSCs nor iPSC-derived neural cultures not-enriched-in-DAn. These findings suggest the presence of molecular defects in PD somatic cells which manifest only upon differentiation into the DAn cells targeted in PD. The methylation profile from PD DAn, but not from controls, resembled that of neural cultures not-enriched-in-DAn indicating a failure to fully acquire the epigenetic identity own to healthy DAn in PD. The PD-associated hypermethylation was prominent in gene regulatory regions such as enhancers and was related to the RNA and/or protein downregulation of a network of transcription factors relevant to PD (FOXA1, NR3C1, HNF4A, and FOSL2). Using a patient-specific iPSC-based DAn model, our study provides the first evidence that epigenetic deregulation is associated with monogenic and sporadic PD. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Impulsive-compulsive behaviors in parkin-associated Parkinson disease

PubMed Central

Fasano, Alfonso; Ginevrino, Monia; Petrucci, Simona; Ricciardi, Lucia; Bove, Francesco; Criscuolo, Chiara; Moccia, Marcello; De Rosa, Anna; Sorbera, Chiara; Bentivoglio, Anna Rita; Barone, Paolo; De Michele, Giuseppe; Pellecchia, Maria Teresa; Valente, Enza Maria

2016-01-01

Objective: The aim of this multicenter, case-control study was to investigate the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease (PD) compared to a group of patients without the mutation. Methods: We compared 22 patients with biallelic parkin mutations (parkin-PD) and 26 patients negative for parkin, PINK1, DJ-1, and GBA mutations (PD-NM), matched for age at onset, disease duration, levodopa, and dopamine agonist equivalent daily dose. A semistructured interview was used to diagnose each of the following ICBs: compulsive sexual behavior, compulsive buying, binge eating, punding, hobbyism, and compulsive medication use. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease–Rating Scale (QUIP-RS) was adopted to rate ICB severity. Results: Frequency of patients with at least one ICB was comparable between parkin-PD and PD-NM. Nevertheless, when analyzing the distribution of specific ICBs, a higher frequency of compulsive shopping, binge eating, and punding/hobbyism was found in the parkin-PD group. Compared to PD-NM, parkin-PD patients with ICB had younger onset age and higher frequency of smokers; in 5 patients, ICB had predated PD onset. Total and partial (compulsive buying, compulsive sexual behavior, binge eating, hobbyism/punding) QUIP-RS scores were higher in patients with parkin-PD compared to patients with PD-NM. Logistic regression analysis showed that the presence of parkin mutations was associated with smoking status and higher QUIP-RS total score. Conclusions: Our data expand the parkin-associated phenotypic spectrum demonstrating higher frequency and severity of specific ICBs, and suggesting an association between the parkin genotype, smoking status, and ICB severity. PMID:27590295

Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted therapy in lung cancer patients.

PubMed

Kamphorst, Alice O; Pillai, Rathi N; Yang, Shu; Nasti, Tahseen H; Akondy, Rama S; Wieland, Andreas; Sica, Gabriel L; Yu, Ke; Koenig, Lydia; Patel, Nikita T; Behera, Madhusmita; Wu, Hong; McCausland, Megan; Chen, Zhengjia; Zhang, Chao; Khuri, Fadlo R; Owonikoko, Taofeek K; Ahmed, Rafi; Ramalingam, Suresh S

2017-05-09

Exhausted T cells in chronic infections and cancer have sustained expression of the inhibitory receptor programmed cell death 1 (PD-1). Therapies that block the PD-1 pathway have shown promising clinical results in a significant number of advanced-stage cancer patients. Nonetheless, a better understanding of the immunological responses induced by PD-1 blockade in cancer patients is lacking. Identification of predictive biomarkers is a priority in the field, but whether peripheral blood analysis can provide biomarkers to monitor or predict patients' responses to treatment remains to be resolved. In this study, we analyzed longitudinal blood samples from advanced stage non-small cell lung cancer (NSCLC) patients ( n = 29) receiving PD-1-targeted therapies. We detected an increase in Ki-67+ PD-1+ CD8 T cells following therapy in ∼70% of patients, and most responses were induced after the first or second treatment cycle. This T-cell activation was not indiscriminate because we observed only minimal effects on EBV-specific CD8 T cells, suggesting that responding cells may be tumor specific. These proliferating CD8 T cells had an effector-like phenotype (HLA-DR + , CD38 + , Bcl-2 lo ), expressed costimulatory molecules (CD28, CD27, ICOS), and had high levels of PD-1 and coexpression of CTLA-4. We found that 70% of patients with disease progression had either a delayed or absent PD-1+ CD8 T-cell response, whereas 80% of patients with clinical benefit exhibited PD-1+ CD8 T-cell responses within 4 wk of treatment initiation. Our results suggest that peripheral blood analysis may provide valuable insights into NSCLC patients' responses to PD-1-targeted therapies.

Impulsive-compulsive behaviors in parkin-associated Parkinson disease.

PubMed

Morgante, Francesca; Fasano, Alfonso; Ginevrino, Monia; Petrucci, Simona; Ricciardi, Lucia; Bove, Francesco; Criscuolo, Chiara; Moccia, Marcello; De Rosa, Anna; Sorbera, Chiara; Bentivoglio, Anna Rita; Barone, Paolo; De Michele, Giuseppe; Pellecchia, Maria Teresa; Valente, Enza Maria

2016-10-04

The aim of this multicenter, case-control study was to investigate the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease (PD) compared to a group of patients without the mutation. We compared 22 patients with biallelic parkin mutations (parkin-PD) and 26 patients negative for parkin, PINK1, DJ-1, and GBA mutations (PD-NM), matched for age at onset, disease duration, levodopa, and dopamine agonist equivalent daily dose. A semistructured interview was used to diagnose each of the following ICBs: compulsive sexual behavior, compulsive buying, binge eating, punding, hobbyism, and compulsive medication use. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was adopted to rate ICB severity. Frequency of patients with at least one ICB was comparable between parkin-PD and PD-NM. Nevertheless, when analyzing the distribution of specific ICBs, a higher frequency of compulsive shopping, binge eating, and punding/hobbyism was found in the parkin-PD group. Compared to PD-NM, parkin-PD patients with ICB had younger onset age and higher frequency of smokers; in 5 patients, ICB had predated PD onset. Total and partial (compulsive buying, compulsive sexual behavior, binge eating, hobbyism/punding) QUIP-RS scores were higher in patients with parkin-PD compared to patients with PD-NM. Logistic regression analysis showed that the presence of parkin mutations was associated with smoking status and higher QUIP-RS total score. Our data expand the parkin-associated phenotypic spectrum demonstrating higher frequency and severity of specific ICBs, and suggesting an association between the parkin genotype, smoking status, and ICB severity. © 2016 American Academy of Neurology.

The Edinburgh Primary Care Depression Study: personality disorder and outcome.

PubMed

Patience, D A; McGuire, R J; Scott, A I; Freeman, C P

1995-09-01

Little is known about the impact of personality pathology on the treatment outcome of major depressive illness in primary care in the UK. Patients meeting criteria for DSM-III major depressive disorder were randomly allocated to one of four treatments each lasting 16 weeks, then followed up for 18 months. Assessments were made of depressive symptoms, personality and social functioning. Personality was assessed at maximum improvement or 16 weeks. The prevalence of personality disorder (PD) in the sample of 113 patients was 26%. Patients with a PD were significantly younger and rated more depressed at entry than patients with no personality disorder (NoPD). On completion of treatment patients with a PD were significantly more depressed and had poorer social functioning than the NoPD group. After 18 months there were no differences in ratings of depression or social functioning between the groups. There was substantial improvement in both the PD and NoPD groups. The presence of personality pathology delays recovery from major depressive illness.

CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

PubMed Central

Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

Panic Disorder and Agoraphobia in OCD patients: clinical profile and possible treatment implications.

PubMed

Torres, Albina R; Ferrão, Ygor A; Shavitt, Roseli G; Diniz, Juliana B; Costa, Daniel L C; do Rosário, Maria Conceição; Miguel, Euripedes C; Fontenelle, Leonardo F

2014-04-01

Panic Disorder (PD) and agoraphobia (AG) are frequently comorbid with obsessive-compulsive disorder (OCD), but the correlates of these comorbidities in OCD are fairly unknown. The study aims were to: 1) estimate the prevalence of PD with or without AG (PD), AG without panic (AG) and PD and/or AG (PD/AG) in a large clinical sample of OCD patients and 2) compare the characteristics of individuals with and without these comorbid conditions. A cross-sectional study with 1001 patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders using several assessment instruments, including the Dimensional Yale-Brown Obsessive-Compulsive Scale and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Bivariate analyses were followed by logistic regression models. The lifetime prevalence of PD was 15.3% (N=153), of AG 4.9% (N=49), and of PD/AG 20.2% (N=202). After logistic regression, hypochondriasis and specific phobia were common correlates of the three study groups. PD comorbidity was also associated with higher levels of anxiety, having children, major depression, bipolar I, generalized anxiety and posttraumatic stress disorders. Other independent correlates of AG were: dysthymia, bipolar II disorder, social phobia, impulsive-compulsive internet use, bulimia nervosa and binge eating disorder. Patients with PD/AG were also more likely to be married and to present high anxiety, separation anxiety disorder, major depression, impulsive-compulsive internet use, generalized anxiety, posttraumatic stress and binge eating disorders. Some distinct correlates were obtained for PD and AG in OCD patients, indicating the need for more specific and tailored treatment strategies for individuals with each of these clinical profiles. Copyright © 2014 Elsevier Inc. All rights reserved.

Outcomes of a peritoneal dialysis program in remote communities within Colombia.

PubMed

Sanabria, Mauricio; Devia, Martha; Hernández, Gilma; Astudillo, Kindar; Trillos, Carlos; Uribe, Mauricio; Latorre, Catalina; Bernal, Astrid; Rivera, Angela

2015-01-01

Colombia is a country of diverse geographic regions, some with mountainous terrain that can make access to urban areas difficult for individuals who live in remote areas. In 2005, a program was initiated to establish remote peritoneal dialysis (PD) centers in Colombia to improve access to PD for patients with end-stage renal disease who face geographic or financial access barriers. The present study was a multi-center cohort observational study of prevalent home PD patients who were at least 18 years of age and were being managed by one of nine established remote PD centers in Colombia over a 2-year period. Data were collected from clinical records, databases, and patient interviews. Patient survival, incidence of peritonitis, and rate of withdrawal from PD therapy were assessed. A total of 345 patients were eligible for the study. The majority (87.8%) of patients lived on one to two times a minimum monthly salary (equivalent to US$243 - US$486). On average, patients traveled 1.2 hours and 4.3 hours from their home to their remote PD center or an urban reference renal clinic, respectively. The incidence rate of peritonitis was 2.54 episodes per 100 patient-months of therapy. A bivariate analysis showed a significantly higher risk of peritonitis in patients who were living on less than one times a monthly minimum salary (p < 0.05) or who had a dirt, cement, or unfinished wood floor (p < 0.05). The 1-year and 2-year patient survival rates were 92.44% and 81.55%, respectively. The 1-year and 2-year technique survival rates were 97.27% and 89.78%, respectively. With the support of remote PD centers that mitigate geographic and financial barriers to healthcare, home PD therapy is a safe and appropriate treatment option for patients who live in remote areas in Colombia. Copyright © 2015 International Society for Peritoneal Dialysis.

Success of Urgent-Start Peritoneal Dialysis in a Large Canadian Renal Program

PubMed Central

Alkatheeri, Ali M.A.; Blake, Peter G.; Gray, Daryl; Jain, Arsh K.

2016-01-01

♦ Background: Many patients start renal replacement therapy urgently on in-center hemodialysis via a central venous catheter, which is considered suboptimal. An alternative approach to manage these patients is to start them on peritoneal dialysis (PD). In this report, we describe the first reported Canadian experience with an urgent-start PD program. Additionally we reviewed the literature in this area. ♦ Methods: In this prospective observational study, we report on our experience in a single academic center. This program started in July 2010. We included patients who initiated PD urgently, that is within 2 weeks of catheter insertion. We followed all incident PD patients until October 2013 for mechanical and infectious complications. Peritoneal dialysis catheters were inserted either percutaneously or laparoscopically and dialysis was initiated in either an inpatient or outpatient setting. ♦ Results: Thirty patients were started on urgent PD during our study period. Follow-up ranged from 28 to 1,050 days. Twenty insertions (66.7 %) were done percutaneously and 10 (33.3%) were laparoscopic. Dialysis was initiated within 2 weeks (range: 0 – 13 days, median = 6 days). Twenty-four patients (80%) started PD in an outpatient setting and 6 patients (20%) required immediate inpatient PD start. Three patients (10%) developed a minor peri-catheter leak during the first week of training that was managed conservatively. There were no episodes of peritonitis or exit-site/tunnel infection during the first 4 weeks post-insertion. Four patients (13.3 %) from the percutaneous insertion group and 2 patients (6.7%) from laparoscopic insertions developed catheter dysfunction due to migration, which was managed by repositioning, without need for catheter replacement or modality switch. ♦ Conclusions: Our results are consistent with other studies in this area and demonstrate that urgent-start PD is an acceptable and safe alternative to hemodialysis in patients who need to start dialysis urgently without established dialysis access. PMID:26374834

Success of Urgent-Start Peritoneal Dialysis in a Large Canadian Renal Program.

PubMed

Alkatheeri, Ali M A; Blake, Peter G; Gray, Daryl; Jain, Arsh K

2016-01-01

♦ Many patients start renal replacement therapy urgently on in-center hemodialysis via a central venous catheter, which is considered suboptimal. An alternative approach to manage these patients is to start them on peritoneal dialysis (PD). In this report, we describe the first reported Canadian experience with an urgent-start PD program. Additionally we reviewed the literature in this area. ♦ In this prospective observational study, we report on our experience in a single academic center. This program started in July 2010. We included patients who initiated PD urgently, that is within 2 weeks of catheter insertion. We followed all incident PD patients until October 2013 for mechanical and infectious complications. Peritoneal dialysis catheters were inserted either percutaneously or laparoscopically and dialysis was initiated in either an inpatient or outpatient setting. ♦ Thirty patients were started on urgent PD during our study period. Follow-up ranged from 28 to 1,050 days. Twenty insertions (66.7%) were done percutaneously and 10 (33.3%) were laparoscopic. Dialysis was initiated within 2 weeks (range: 0-13 days, median = 6 days). Twenty-four patients (80%) started PD in an outpatient setting and 6 patients (20%) required immediate inpatient PD start. Three patients (10%) developed a minor peri-catheter leak during the first week of training that was managed conservatively. There were no episodes of peritonitis or exit-site/tunnel infection during the first 4 weeks post-insertion. Four patients (13.3%) from the percutaneous insertion group and 2 patients (6.7%) from laparoscopic insertions developed catheter dysfunction due to migration, which was managed by repositioning, without need for catheter replacement or modality switch. ♦ Our results are consistent with other studies in this area and demonstrate that urgent-start PD is an acceptable and safe alternative to hemodialysis in patients who need to start dialysis urgently without established dialysis access. Copyright © 2016 International Society for Peritoneal Dialysis.

Peritonitis remains the major clinical complication of peritoneal dialysis: the London, UK, peritonitis audit 2002-2003.

PubMed

Davenport, Andrew

2009-01-01

Over the past two decades, the rate of peritonitis in patients treated by peritoneal dialysis (PD) has been significantly reduced. However, peritonitis remains a major complication of PD, accounting for considerable mortality and hospitalization among PD patients. To compare the outcome of peritonitis in a large unselected group of PD patients with that from single-center and selected groups. We audited the outcome of peritonitis in PD patients attending the 12 PD units in the Thames area in 2002 and 2003. There were 538 patients on continuous ambulatory PD (CAPD) and 325 patients on automated PD (APD) and/or continuous cycling PD (CCPD) at the end of 2002, and 635 CAPD and 445 APD/CCPD patients at the end of 2003. There were 1467 episodes of PD peritonitis during the 2-year period, including 129 recurrent episodes, with the average number of months between peritonitis episodes being 14.7 for CAPD and 18.1 for APD/CCPD, p < 0.05. However there was considerable variation between units. Coagulase-negative staphylococcus (CoNS) was the most common cause, accounting for around 30% of all peritonitis episodes, including recurrences, followed by non-pseudomonas gram negatives and Staphylococcus aureus. Cure rates were 77.2% for CoNS, 46.6% for S. aureus, and 7.7% for methicillin-resistant S. aureus. The cure rate for pseudomonas was 21.4%, and other gram negatives 56.7%. In total, there were 351 episodes of culture-negative peritonitis, with an average cure rate of 76.9%. Cure rates were higher for those centers that used a combination of intraperitoneal gentamicin and cephalosporins than those centers that used oral-based regimes. A total of 296 PD catheters were removed as a direct consequence of PD peritonitis: 121 due to gram-positive and 123 due to gram-negative organisms. Only 49 catheters were reinserted and the patients returned to PD. 52 patients died during or subsequent to their episode of PD peritonitis, with an overall mortality rate of 3.5%. This audit showed that, in a large unselected population of PD patients, the incidence of peritonitis was significantly greater than that reported in single-center short-term studies, and varied from unit to unit. Similarly, the success of treating PD peritonitis varied not only with the cause of the infection but also from unit to unit. PD peritonitis remains a major cause of patients discontinuing PD and switching to hemodialysis.

The Impact of PD-L1 Expression in Patients with Metastatic GEP-NETs

PubMed Central

Kim, Seung Tae; Ha, Sang Yun; Lee, Sujin; Ahn, Soomin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Kim, Kyoung-Mee; Park, Young Suk

2016-01-01

Programmed death-ligand 1 (PD-L1), which is expressed on many cancer cells, interacts with PD1 expressed on the surface of T cells, inhibiting the T cells and blocking the antitumor immune response. Expression of PD-L1 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been studied. We investigated the impact of PD-L1 expression in 32 patients with metastatic GEP-NET. The expression of PD-L1 was evaluated using an anti-PD-L1 immunohistochemistry (IHC) antibody optimized for staining of formalin-fixed paraffin-embedded (FFPE) tissue samples. The correlation between PD-L1 and clinicopathological data including survival and response to systemic treatments was analyzed. Primary sites were 24 foregut-derived GEP-NETs, including stomach (n=1), duodenum (n=2), biliary tract (n=7), and pancreas (n=14), and 8 hindgut-derived GEP-NETs of the distal colon and rectum. Among the 32 patients with metastatic GEP-NET analyzed in this study, 7 (21.9%) had expression of PD-L1 in tumor tissues. Expression of PD-L1 was significantly associated with high-grade WHO classification (grade 3) (p=0.008) but not with gender, primary site, and number of metastatic sites (p>0.05). The status of PD-L1 expression was statistically associated with progression-free survival (PFS) for first-line systemic treatment (p=0.047). Moreover, the status of PD-L1 expression could significantly predict overall survival (p=0.037). The expression of PD-L1 was associated with higher WHO tumor grade (grade 3) in metastatic GEP-NETs. PD-L1 expression had both predictive and prognostic value for survival of patients with metastatic GEP-NETs. PMID:26958083

Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors.

PubMed

De Martin, Eleonora; Michot, Jean-Marie; Papouin, Barbara; Champiat, Stéphane; Mateus, Christine; Lambotte, Olivier; Roche, Bruno; Antonini, Teresa Maria; Coilly, Audrey; Laghouati, Salim; Robert, Caroline; Marabelle, Aurélien; Guettier, Catherine; Samuel, Didier

2018-06-01

Immunotherapy for metastatic cancer can be complicated by the onset of hepatic immune-related adverse events (IRAEs). This study compared hepatic IRAEs associated with anti-programmed cell death protein 1 (PD-1)/PD ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibodies (mAbs). Among 536 patients treated with anti-PD-1/PD-L1 or CTLA-4 immunotherapies, 19 (3.5%) were referred to the liver unit for grade ≥3 hepatitis. Of these patients, nine had received anti-PD-1/PD-L1 and seven had received anti-CTLA-4 mAbs, in monotherapy or in combination with anti-PD-1. Liver investigations were undertaken in these 16 patients, including viral assays, autoimmune tests and liver biopsy, histological review, and immunostaining of liver specimens. In the 16 patients included in this study, median age was 63 (range 33-84) years, and nine (56%) were female. Time between therapy initiation and hepatitis was five (range, 1-49) weeks and median number of immunotherapy injections was two (range, 1-36). No patients developed hepatic failure. Histology related to anti-CTLA-4 mAbs demonstrated granulomatous hepatitis including fibrin ring granulomas and central vein endotheliitis. Histology related to anti-PD-1/PD-L1 mAbs was characterised by lobular hepatitis. The management of hepatic IRAEs was tailored according to the severity of both the biology and histology of liver injury: six patients improved spontaneously; seven received oral corticosteroids at 0.5-1 mg/kg/day; two were maintained on 0.2 mg/kg/day corticosteroids; and one patient required pulses and 2.5 mg/kg/day of corticosteroids, and the addition of a second immunosuppressive drug. In three patients, immunotherapy was reintroduced without recurrence of liver dysfunction. Acute hepatitis resulting from immunotherapy for metastatic cancer is rare (3.5%) and, in most cases, not severe. Histological assessment can distinguish between anti-PD-1/PD-L1 and anti-CTLA-4 mAb toxicity. The severity of liver injury is helpful for tailoring patient management, which does not require systematic corticosteroid administration. Immunotherapy for metastatic cancer can be complicated by immune-related adverse events in the liver. In patients receiving immunotherapy for metastatic cancer who develop immune-mediated hepatitis, liver biopsy is helpful for the diagnosis and evaluation of the severity of liver injury. This study demonstrates the need for patient-oriented management, which could eventually avoid unnecessary systemic corticosteroid treatment. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

T cell Bim levels reflect responses to anti–PD-1 cancer therapy

PubMed Central

Dronca, Roxana S.; Liu, Xin; Harrington, Susan M.; Chen, Lingling; Cao, Siyu; Kottschade, Lisa A.; McWilliams, Robert R.; Block, Matthew S.; Nevala, Wendy K.; Thompson, Michael A.; Mansfield, Aaron S.; Park, Sean S.; Markovic, Svetomir N.

2016-01-01

Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+ T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility. PMID:27182556

Cognitive functions in Parkinson's disease: relation to disease severity and hallucination.

PubMed

Wakamori, Takaaki; Agari, Takashi; Yasuhara, Takao; Kameda, Masahiro; Kondo, Akihiko; Shinko, Aiko; Sasada, Susumu; Sasaki, Tatsuya; Furuta, Tomohisa; Date, Isao

2014-04-01

We wished to relate severity of Parkinson's disease (PD) with cognitive function in relation to cerebral blood flow (CBF). Eighty-one consecutive PD patients were enrolled in this study. We used Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Third edition (WAIS-III) to evaluate cognitive functions, and three-dimensional stereotactic ROI template (3DSRT) and Statistical Parametric Mapping (SPM) 8 to evaluate single photon emission CT (SPECT) recordings of regional CBF. The mean MMSE score of PD patients was 27.4 ± 2.4. The scores of most patients were higher than 23/30. On the other hand, the mean Full-scale IQ of PD patients was 88.4 ± 17.3 in WAIS-III, which was lower than that of normal controls. In particular, visuospatial function score of most patients was lower. There was significant correlation between cognitive scores and Hoehn & Yahr stage and hallucinatory episodes. PD Patients with stage III and IV showed significant deterioration in cognitive functions compared to stage II patients. Analysis of CBF revealed relative reductions in perfusion in the cerebral cortex relative to that in normal control. SPM 8 showed that cognitive functions in PD patients were positively correlated with rCBF in the thalamus and cingulate gyrus. This is the study to demonstrate the cognitive impairments in PD patients using WAIS-III. Visuospatial dysfunction might be caused by decrease in rCBF in the parietal and occipital lobes and dorsolateral prefrontal cortex. The severity of cognitive impairments in PD patients was correlated with disease severity and hallucinatory episodes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Parkinson Patients' Initial Trust in Avatars: Theory and Evidence.

PubMed

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson's disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients' interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research.

Personality Traits and Cortical Activity Affect Gambling Behavior in Parkinson's Disease.

PubMed

Balconi, Michela; Siri, Chiara; Meucci, Nicoletta; Pezzoli, Gianni; Angioletti, Laura

2018-03-26

Pathological gambling (PG) in Parkinson's disease (PD) manifests as a persistent and uncontrollable gambling behavior, characterized by dysfunctional decision-making and emotional impairment related to high-risk decisions. The aim of this study was to explore the relationship between personality traits and prefrontal cortex activity in PD patients with or without PG. Thus, hemodynamic cortical activity measured by functional near-infrared spectroscopy (fNIRS) and Iowa Gambling Task (IGT) performance were recorded in forty-six PD patients, divided into three groups according to their gambling status: PD patients with active gambling behavior (PDG); PD patients who remitted from PG (PDNG); and a control group (CG) composed by patients with PD only. Results indicates that gambling behavior in PD patients is strongly predictive of dysfunctional cognitive strategy; affecting anomalous cortical response with a left hemispheric unbalance in dorsal areas; and it is related to more reward sensitivity than impulsivity personality components. PDG patients differed from PDNG and CG from both behavioral and brain response to decision-making. Overall, these effects confirm a pathological condition related to cognitive and emotional aspects which makes the patients with PGD victims of their dysfunctional behavior.

Treatment of Parkinson's disease: a survey of patients and neurologists.

PubMed

Fargel, Matthias; Grobe, Bernd; Oesterle, Eberhard; Hastedt, Claudia; Rupp, Markus

2007-01-01

The treatment of Parkinson's disease (PD) is complex and highly individual. The choice between available treatment options depends on clinical characteristics such as the patient's age, disease severity and presence of comorbidities, lifestyle characteristics and preferences, costs of different medications and awareness and perception of available treatment options, and education of the treating physician. The impact of PD treatment regimens on patients' health-related quality of life (QOL) is also an important healthcare feature. The objective of the present study was to assess treatment options, treatment satisfaction and opinions about treatment improvements in patients with PD and neurologists treating the disease. Two surveys using face-to-face interviews and an additional phone survey were carried out in the US and five European countries (France, Germany, Italy, Spain and the UK). Patients with early and advanced stages of PD were included. To participate in the neurologist survey, neurologists were required to personally treat ten or more PD patients per month, including both early and advanced stage patients. Interviews consisted of a mix of closed and open-ended questions; some of these questions involved show cards. Of the 500 patients who were surveyed, 49% had early and 51% had advanced PD. Early-stage PD patients, both in the US and Europe, take a mean of 3.2 tablets daily of PD-medication. In contrast, the mean daily tablet load of PD medication is much higher for advanced-stage patients (9.9 and 8.4 tablets in the US and Europe, respectively). Tablet load was perceived as a major problem; the majority of patients wished to see improvements regarding daily medication intake and expressed interest in other delivery systems such as patches. Overall, patients rated their treatment with a score of 6.6 points (6.7 for early-stage and 6.6 for advanced-stage patients) [scale of 1-10; 10 being highest]. Physicians (n = 592) were satisfied with a number of current PD medications and assumed they improve the QOL of the patients. They regarded efficacy and safety as the most important features for the improvement of PD medication. Further research is needed into PD treatment options not only for symptom alleviation but for better delivery systems that could improve compliance and QOL for patients with PD. Treatment guidelines need to incorporate QOL aspects and general communication between the health professional and the patient.

Discussing sexuality with patients with Parkinson's disease: a survey among Dutch neurologists.

PubMed

van Hees, Petra J M; van der Plas, Anton A; van Ek, Gaby F; Putter, Hein; Den Oudsten, Brenda L; den Ouden, Marjolein E M; Elzevier, Henk W

2017-03-01

Sexual functioning is often impaired in patients with Parkinson's disease (PD) and may affect quality of life of patients and their spouse. However, little is known about the practice patterns of neurologists with regard to discussing sexuality in this field. The aim of this cross-sectional study was to evaluate to what extent neurologists discuss sexuality with PD patients. A 22-item questionnaire was sent to 139 neurologists specializing in PD. The survey contained questions about their attitudes, knowledge, and practice patterns with respect to sexual dysfunction (SD) in patients with PD. The response rate of the survey was 66.9%. Most participants (56.8%) stated that they address sexuality in less than half of their PD patients. High age of patients (42.0%), insufficient consultation time (37.5%), and a lack of patients' initiative to raise the topic themselves (36.4%) were frequently reported barriers towards discussing sexuality. The majority of participants considered that discussing sexuality is a responsibility that lay with neurologists (85.2%), nurses (73.9%), and patients (72.7%). One quarter of the neurologists reported to have insufficient or no knowledge on SD. The majority of participants regarded screening for SD important or slightly important (85.2%). A large proportion of Dutch neurologists specializing in PD do not routinely discuss sexuality with their PD patients. Sexual healthcare in PD patients may benefit from time-efficient tools and agreements on who is responsible for discussing SD. Furthermore, recommendations in PD guidelines on screening and managing SD should be adapted to fit everyday practice.

Determining the efficacy of rasagiline in reducing bradykinesia among Parkinson's disease patients: a review.

PubMed

Silver, Dee E; Buck, Philip O

2011-09-01

Bradykinesia has a significant impact on the lives of Parkinson's disease (PD) patients. Consequently, treating this symptom is of particular concern for patients and clinicians. A number of studies have documented the efficacy of rasagiline in reducing the severity of PD symptoms. To summarize studies that specifically examined the impact of rasagiline on bradykinesia symptoms in PD patients across disease severity. The EMBASE database was searched for relevant articles published between 2000 and November 2010. Three studies were identified that explicitly examined the effect of rasagiline on the bradykinesia subscale of the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. In each, 1 mg/day rasagiline significantly reduced bradykinesia scores in patients. As a monotherapy or an adjunctive therapy, rasagiline is an effective drug for reducing the severity of bradykinesia in PD patients. Copyright © 2011 Informa Healthcare USA, Inc.

Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations.

PubMed

Limousin, Nadège; Konofal, Eric; Karroum, Elias; Lohmann, Ebba; Theodorou, Ioannis; Dürr, Alexandra; Arnulf, Isabelle

2009-10-15

Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35-60 years, from seven families) and 11 sex-matched patients with iPD (aged 51-65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent.

Predictive Value of Soluble Programmed Death-1 for Severe Sepsis and Septic Shock During the First Week in an Intensive Care Unit.

PubMed

Zhao, Yongzhen; Jia, Yumei; Li, Chunsheng; Shao, Rui; Fang, Yingying

2018-04-26

Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) exists in both membrane-bound and soluble forms. In this study, we evaluated the predictive value of soluble PD-1 (sPD-1) for severity and 28-day mortality in patients with severe sepsis and septic shock during the first week in an intensive care unit (ICU). In this prospective cohort study, patients were classified into the severe sepsis group or the septic shock group according to the severity of their condition on ICU admission. All patients were also separated into the survivor or nonsurvivor groups according to their 28-day outcomes. Peripheral blood sPD-1 and soluble PD-L1 (sPD-L1) levels, PD-1 expression on CD4 and CD8 T cells, and PD-L1 expression on monocytes were measured and compared between the groups on days 1 and 7 after ICU admission. In all, 45 healthy volunteers and 112 patients were recruited. Serum sPD-1 levels were positively correlated with the severity of sepsis, sPD-L1 levels, PD-1 expression on CD4 or CD8 T cells, and PD-L1 expression on monocytes. The sPD-1 was an independent predictive factor for 28-day mortality both on day 1 and day 7. The area under the curve (AUC) of the sPD-1 on day 7 (0.871) was higher than that on day 1 (0.785) (P < 0.05), and better than the AUC of the percentages of PD-L1 on monocytes (0.770) on day 7 (P < 0.05). Serum sPD-1 shows valuable predictive ability for the severity and 28-day mortality of severe sepsis and septic shock during the first week of ICU treatment.

MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients.

PubMed

Tolosa, Eduard; Botta-Orfila, Teresa; Morató, Xavier; Calatayud, Carles; Ferrer-Lorente, Raquel; Martí, María-José; Fernández, Manel; Gaig, Carles; Raya, Ángel; Consiglio, Antonella; Ezquerra, Mario; Fernández-Santiago, Rubén

2018-05-31

MicroRNA (miRNA) misregulation in peripheral blood has been linked to Parkinson disease (PD) but its role in the disease progression remains elusive. We performed an explorative genome-wide study of miRNA expression levels in dopaminergic neurons (DAn) from PD patients generated by somatic cell reprogramming and induced pluripotent stem cells differentiation. We quantified expression levels of 377 miRNAs in DAn from 3 sporadic PD patients (sPD), 3 leucine-rich repeat kinase 2-associated PD patients (L2PD) (total 6 PD), and 4 healthy controls. We identified differential expression of 10 miRNA of which 5 were upregulated in PD (miR-9-5p, miR-135a-5p, miR-135b-5p, miR-449a, and miR-449b-5p) and 5 downregulated (miR-141-3p, miR-199a-5p, miR-299-5p, miR-518e-3p, and miR-519a-3p). Changes were similar in sPD and L2PD. Integrative analysis revealed significant correlations between miRNA/mRNA expression. Moreover, upregulation of miR-9-5p and miR-135b-5p was associated with downregulation of transcription factors related to the DNA hypermethylation of enhancer elements in PD DAn (FOXA1 and NR3C1). In summary, miRNA changes are associated with monogenic L2PD and sPD and co-occur with epigenetic changes in DAn from PD patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Factors influencing psychosocial adjustment and quality of life in Parkinson patients and informal caregivers.

PubMed

Navarta-Sánchez, María Victoria; Senosiain García, Juana M; Riverol, Mario; Ursúa Sesma, María Eugenia; Díaz de Cerio Ayesa, Sara; Anaut Bravo, Sagrario; Caparrós Civera, Neus; Portillo, Mari Carmen

2016-08-01

The influence that social conditions and personal attitudes may have on the quality of life (QoL) of Parkinson's disease (PD) patients and informal caregivers does not receive enough attention in health care, as a result of it not being clearly identified, especially in informal caregivers. The aim of this study was to provide a comprehensive analysis of psychosocial adjustment and QoL determinants in PD patients and informal caregivers. Ninety-one PD patients and 83 caregivers participated in the study. Multiple regression analyses were performed including benefit finding, coping, disease severity and socio-demographic factors, in order to determine how these aspects influence the psychosocial adjustment and QoL in PD patients and caregivers. Regression models showed that severity of PD was the main predictor of psychosocial adjustment and QoL in patients. Nevertheless, multiple regression analyses also revealed that coping was a significant predictor of psychosocial adjustment in patients and caregivers. Furthermore, psychosocial adjustment was significantly related to QoL in patients and caregivers. Also, coping and benefit finding were predictors of QoL in caregivers but not in patients. Multidisciplinary interventions aimed at improving PD patients' QoL may have more effective outcomes if education about coping skills, and how these can help towards a positive psychosocial adjustment to illness, were included, and targeted not only at patients, but also at informal caregivers.

Group patient visits for Parkinson disease: a randomized feasibility trial.

PubMed

Dorsey, E R; Deuel, L M; Beck, C A; Gardiner, I F; Scoglio, N J; Scott, J C; Marshall, F J; Biglan, K M

2011-05-03

Group patient visits are medical appointments shared among patients with a common medical condition. This care delivery method has demonstrated benefits for individuals with chronic conditions but has not been evaluated for Parkinson disease (PD). We conducted a 12-month, randomized trial of group patient visits vs usual (one-on-one) care for patients with PD. Visits were led by one of 3 study physicians, included patients and caregivers, and lasted approximately 90 minutes. Those receiving group visits had 4 sessions over 12 months. The primary outcome measure was feasibility as measured by the ability to recruit participants and by the proportion of participants who completed the study. The primary efficacy outcome was quality of life as measured by the PD Questionnaire-39. Thirty patients and 27 caregivers enrolled in the study. Thirteen of the 15 patients randomized to group patient visits and 14 of the 15 randomized to usual care completed the study. Quality of life measured 12 months after baseline between the 2 groups was not different (25.9 points for group patient visits vs 26.0 points for usual care; p = 0.99). Group patient visits may be a feasible means of providing care to individuals with PD and may offer an alternative or complementary method of care delivery for some patients and physicians. This study provides Class II evidence that group patient visits did not improve quality of life for individuals with PD over a 1-year period.

Outcomes of Peritonitis in Children on Peritoneal Dialysis: A 25-Year Experience at Severance Hospital

PubMed Central

Lee, Kyong Ok; Park, Se Jin; Kim, Ji Hong; Lee, Jae Seung; Kim, Pyung Kil

2013-01-01

Purpose Relatively little is known on the microbiology, risk factors and outcomes of peritoneal dialysis (PD)-associated peritonitis in Korean children. We performed this study in order to evaluate the incidence, treatment and clinical outcomes of peritonitis in pediatric PD patients at Severance Hospital. Materials and Methods We analyzed data from 57 PD patients younger than 18 years during the period between June 1, 1986 and December 31, 2011. The collected data included gender, age at commencement of PD, age at peritonitis, incidence of peritonitis, underlying causes of end stage renal disease, microbiology of peritonitis episodes, antibiotics sensitivity, modality and outcomes of PD. Results We found 56 episodes of peritonitis in 23 of the 57 PD patients (0.43 episodes/patient-year). Gram-positive bacteria were the most commonly isolated organisms (40 episodes, 71.4%). Peritonitis developed in 17 patients during the first 6 months following initiation of PD (73.9%). Peritonitis episodes rarely resulted in relapse or the need for permanent hemodialysis and no patient deaths were directly attributable to peritonitis. Antibiotic regimens included cefazolin+tobramycin from the years of 1986 to 2000 and cefazolin+ceftazidime from the years of 2001 to 2011. While antibiotic therapy was successful in 48 episodes (85.7%), the treatment was ineffective in 8 episodes (14.3%). The rate of continuous ambulatory PD (CAPD) peritonitis was statistically higher than that of automated PD (APD) (p=0.025). Conclusion Peritonitis was an important complication of PD therapy and we observed a higher incidence of PD peritonitis in patients with CAPD when compared to APD. PMID:23709435

Outcome and complications in peritoneal dialysis patients: a five-year single center experience.

PubMed

Alwakeel, Jamal S; Alsuwaida, Abdulkareem; Askar, Akram; Memon, Nawaz; Usama, Saira; Alghonaim, Mohammed; Feraz, Niaz A; Shah, Iqbal Hamid; Wilson, Hamsaveni

2011-03-01

Peritoneal dialysis (PD) is one of the modes of renal replacement therapy being utilized for the management of end-stage renal failure in King Khalid University Hospital, King Saud University, Riyadh, for more than two decades. The aim of this study was to evaluate the complications related to PD as well as its outcome in patients on this mode of therapy during the period between January 2004 and December 2008. There were 72 patients included in the study, of whom 43 were females. The average age was 50.7 ± 30.1 years (14-88 years). Diabetes was the leading cause of end-stage renal disease (ESRD) seen in 40.2% of the study patients. Twenty-eight patients (38.9%) were on continuous ambulatory peritoneal dialysis (CAPD) and 44 (61.1%) were on automated PD (nocturnal intermittent peritoneal dialysis, NIPD or continuous cycler peritoneal dialysis, CCPD). The mean duration on PD of the study patients was 25.5 ± 16.58 months (1-60 months). The peritonitis rate was one episode per 24.51 patient-months or one episode per 2.04 patient-years. The incidence of peritonitis per person-year was calculated as 0.42. The leading causative agent for peritonitis was Staphylococcus (32%). Exit-site infection (ESI) rate was one episode per 56.21 patient-months. The incidence of ESI was 0.214 per person-years. The most common infective organism for ESI was Pseudomonas aeru-ginosa (58.8%). At the end of 5 years, 35 patients were continuing on PD, 13 patients were shifted to hemodialysis (HD), nine patients underwent renal transplantation, and six patients were transferred to other centers. Among the 13 patients who were shifted to HD, four patients had refractory peritonitis, four others had catheter malfunction, three patients had inadequate clearance on PD and two patients had lack of compliance. A total of 11 patients died during the study period, giving an overall mortality rate of 15.27% for the five-year period. Our study suggests that there has been considerable improvement in overall outcome and mortality in patients on PD. Additionally, a marked reduction in the infectious and non-infectious complications was noted with the peritonitis and ESI rates in our center being comparable to other studies and international guidelines.

Evaluation of autonomic functions of patients with multiple system atrophy and Parkinson's disease by head-up tilt test.

PubMed

Watano, Chikako; Shiota, Yuri; Onoda, Keiichi; Sheikh, Abdullah Md; Mishima, Seiji; Nitta, Eri; Yano, Shozo; Yamaguchi, Shuhei; Nagai, Atsushi

2018-02-01

The aim of this study was to evaluate the autonomic neural function in Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test and spectral analysis of cardiovascular parameters. This study included 15 patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects. High frequency power of the RR interval (RR-HF), the ratio of low frequency power of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively. Both patients with PD and MSA showed orthostatic hypotension and lower parasympathetic function (RR-HF) at tilt position as compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was significantly high in patients with PD than MSA at supine position. RR-LF/HF tended to increase in MSA and HC, but decreased in PD by tilting. Consequently, the change of the ratio due to tilting (ΔRR-LF/HF) was significantly lower in patients with PD than in HC subjects. Further analysis showed that compared to mild stage of PD, RR-LF/HF at the supine position was significantly higher in advanced stage. By tilting, it was increased in mild stage and decreased in the advanced stage of PD, causing ΔRR-LF/HF to decrease significantly in the advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular parameters is useful to identify sympathetic and parasympathetic disorders in MSA and PD. High cardiac sympathetic function at the supine position, and its reduction by tilting might be a characteristic feature of PD, especially in the advanced stage.

Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma

PubMed Central

Kiyasu, Junichi; Miyoshi, Hiroaki; Hirata, Akie; Arakawa, Fumiko; Ichikawa, Ayako; Niino, Daisuke; Sugita, Yasuo; Yufu, Yuji; Choi, Ilseung; Abe, Yasunobu; Uike, Naokuni; Nagafuji, Koji; Okamura, Takashi; Akashi, Koichi; Takayanagi, Ryoichi; Shiratsuchi, Motoaki

2015-01-01

Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1+ DLBCL. We performed PD-L1/PAX5 double immunostaining in 1253 DLBCL biopsy samples and established a new definition of PD-L1+ DLBCL. We also defined the criteria for microenvironmental PD-L1+ (mPD-L1+) DLBCL (ie, PD-L1– DLBCL in which PD-L1+ nonmalignant cells are abundant in the tumor microenvironment). Of the 273 patients whose clinical information was available, quantitative analysis of PD-1+ tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1+ and mPD-L1+ DLBCL were 11% and 15.3%, respectively. Both PD-L1+ and mPD-L1+ DLBCL were significantly associated with non–germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1+ TILs was significantly higher in GCB-type tumors and lower in mPD-L1– and PD-L1+ DLBCL. Patients with PD-L1+ DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1– DLBCL (P = .0009). In contrast, there was no significant difference in OS between mPD-L1+ and mPD-L1– DLBCL (P = .31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1+ DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup. PMID:26239088

Effects of physical exercise programs on cognitive function in Parkinson’s disease patients: A systematic review of randomized controlled trials of the last 10 years

PubMed Central

Iop, Rodrigo da Rosa; de Oliveira, Laiana Cândido; Boll, Alice Mathea; de Alvarenga, José Gustavo Souza; Gutierres Filho, Paulo José Barbosa; de Melo, Lídia Mara Aguiar Bezerra; Xavier, André Junqueira; da Silva, Rudney

2018-01-01

Background Given the relative importance of cognitive impairment, there was considerable interest in identifying the cognitive profile of PD patients, in order to ensure specific and appropriate therapeutic interventions. Purpose To determine the effects of physical exercise programs on cognitive function in PD patients, compared with the control group. Data sources Medline, Cochrane, Scopus, PEDro and Web of Science (last searched in September 2016). Study selection Randomized clinical trials examining the effects of physical exercise programs and cognitive function in PD patients. Nine studies fulfilled the selection criteria and were included in this review. Data extraction Characteristics of the publication, characteristics of the participants, test used for cognitive screening, cognitive domain assessed, tools used to assess cognitive function, characteristics of the experimental intervention, characteristics of the control group, mean results and standard deviation of function cognitive. The PEDro score was used to evaluate methodological quality. Data synthesis Most eligible studies showed good methodological quality based on the PEDro scale. Studies have shown that adapted tango for PD patients, cognitive training combined with motor training, and treadmill training promote the preservation or improvement of cognitive function in PD patients. Limitations The diversity of cognitive tests used to assess cognitive function and the high heterogeneity identified between the physical exercise programs. Conclusions Physical exercise programs promote positive and significant effects on global cognitive function, processing speed, sustained attention and mental flexibility in PD patients, at a mild to moderate stage for patients with a 6-year clinical diagnosis of PD. However, treadmill training performed 3 times a week for about 60 minutes and for a period of 24 weeks produced larger improvements in cognition. PMID:29486000

PD-L1 expression as poor prognostic factor in patients with non-squamous non-small cell lung cancer

PubMed Central

Zheng, Xiaobin; Li, Zhanyu; Sun, Tiantian; Li, Jie; Wang, Shuncong; Zhou, Xiuling; Sun, Hongliu; Cheng, Zhibin; Zhang, Hongyu; Ma, Haiqing

2017-01-01

Objectives The role of programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC), especially according to histologic type, remains controversial. The purpose of this study was to assess PD-L1 expression and its association with overall survival (OS) and clinicopathologic characteristics in NSCLC. Materials and methods Formalin-fixed paraffin-embedded specimens were obtained from 108 patients with surgically resected primary NSCLC. PD-L1 expression was assessed via immunohistochemistry using a histochemistry score system. The relationship between OS or clinicopathologic characteristics and PD-L1 expression was evaluated via the Kaplan-Meier method and Cox proportional hazards model, respectively. Results Of 108 NSCLC specimens, 44 had high PD-L1 expression, which was highly associated with histologic type (p = 0.003). Patients without PD-L1 expression had remarkably longer OS than those with PD-L1 expression (median OS: 96 months vs. 33 months, p < 0.001). In the subgroup analysis of non-squamous cell carcinoma, OS was more favorable in those without PD-L1 expression than in those with PD-L1 expression (median OS: 113 months vs. 37 months, p < 0.001). Multivariate analysis revealed that PD-L1 expression (95% confidence interval 1.459-4.520, p < 0.001), male sex and higher tumor-node-metastasis stage were significantly correlated with shorter OS. Conclusions This study demonstrated that PD-L1 expression is an independent prognostic factor for poor survival in NSCLC patients, especially those with non-squamous NSCLC. PMID:28938570

Lower urinary tract symptoms in Parkinson's disease: Prevalence, aetiology and management.

PubMed

McDonald, Claire; Winge, Kristian; Burn, David J

2017-02-01

Lower urinary tract symptoms (LUTS) are common in Parkinson's disease (PD), effecting 27-85% of patients with PD. Irritative symptoms predominate and urodynamic studies confirm high prevalence of detrusor overactivity in PD. LUTS are present early in PD and are more common in PD than in age matched controls. The assessment of LUTS in PD is complicated by coexisting bradykinesia and cognitive impairment. Although LUTS become more troublesome as PD progresses it remains unclear if LUTS severity correlates with motor symptoms and/or duration of PD. The underlying cause of LUTS in PD remains to be fully elucidated. Animal and human studies suggest the net effect of the basal ganglia is to supress micturition. Although LUTS are a common in PD, few studies have examined the assessment and management of LUTS specifically in patients with PD. Pilot studies have suggested that bladder training, antimuscarinic drugs and intravesical botulinum toxin maybe helpful but these trials have been small and frequently lacked a suitable control group making them vulnerable to the placebo effect. Furthermore the adverse effects of antimuscarinic drugs on cognitive and gastrointestinal function may limit the use of these drugs in PD. In this review we summarise the literature describing the prevalence of LUTS in PD, discuss the emerging data delineating the underlying pathophysiology of LUTS and examine interventions helpful in the management of LUTS in people with PD. Copyright © 2016. Published by Elsevier Ltd.

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

PubMed Central

Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

2014-01-01

The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD. PMID:25426023

Morphologic changes in the mesolimbic pathway in Parkinson's disease motor subtypes.

PubMed

Nyberg, Eric M; Tanabe, Jody; Honce, Justin M; Krmpotich, Theodore; Shelton, Erika; Hedeman, Jessica; Berman, Brian D

2015-05-01

Parkinson's disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy. Cortical atrophy patterns may further help distinguish between PD motor subtypes. Comparable differences in subcortical volumes have not been found. Twenty-one cognitively intact and treated PD patients, including 12 tremor dominant (TD) subtype, Nine postural instability gait dominant (PIGD) subtype, and 20 matched healthy control subjects underwent 3.0 T high-resolution structural MRI scanning. Subcortical volumetric analysis was performed using FreeSurfer and shape analysis was performed with FIRST to assess for differences between PD patients and controls and between PD subtypes. No significant differences in subcortical volumes were found between motor PD subtypes, but comparing grouped PD patients with controls revealed a significant increase in hippocampal volume in PD patients (p = 0.03). A significant shape difference was detected in the right nucleus accumbens (NAcc) between PD and controls and between motor subtypes. Shape differences were driven by positive deviations in the TD subtype. Correlation analysis revealed a trend between hippocampal volume and decreasing MDS-UPDRS (p = 0.06). While no significant differences in subcortical volumes between PD motor subtypes were found, increased hippocampal volumes were observed in PD patients compared to controls. Right NAcc shape differences in PD patients were driven by changes in the TD subtype. These unexpected findings may be related to the effects of chronic dopaminergic replacement on the mesolimbic pathway. Further studies are needed to replicate and determine the clinical significance of such morphologic changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diverse cutaneous adverse eruptions caused by anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies: clinical features and management.

PubMed

Shen, John; Chang, Jason; Mendenhall, Melody; Cherry, Grace; Goldman, Jonathan W; Kulkarni, Rajan P

2018-01-01

The anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these immunotherapies can also result in diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. The objective was to provide clinical and histopathologic descriptions of the variety of cutaneous adverse events seen in patients who received anti-PD-1/PD-L1 treatment and discuss their management. Patients with advanced cancers in clinical trials at University of California Los Angeles (UCLA), receiving anti-PD-1/PD-L1 treatment between 2012 and 2016 who developed cutaneous eruptions and were evaluated in the dermatology clinic were included in this retrospective case series study. A total of 16 patients were included in this study; of these, five were treated with pembrolizumab alone, two with avelumab alone, eight with nivolumab plus ipilimumab and one with nivolumab plus T-Vec. Of these 16 patients, eight had received systemic chemotherapy, six had received radiotherapy, and one had received trememlimumab prior to the immunotherapies described in this study. Cutaneous eruptions occurred at variable times, from week 1 to 88, with a median of 11.5 weeks; the morphologies included lichenoid, bullous, psoriasiform, macular, morbiliform appearances, and alopecia which were confirmed histopathologically in several of the cases. All cutaneous immune-related adverse events were either grade 1 or 2. Ten patients were treated with topical corticosteroids, and one also received NBUVB. Four patients eventually required systemic steroids. Three required discontinuation of their anti-PD-1/PD-L1 therapy secondary to the cutaneous eruptions. There are several different types of adverse cutaneous morphologies that may be seen with administration of PD-1 and PD-L1 inhibitors. Identifying the patterns of eruption may assist in prompt treatment. Most eruptions could be managed with topical corticosteroids and without discontinuation of the systemic treatment.

Early Parkinson's disease patients on rasagiline present with better odor discrimination.

PubMed

Haehner, Antje; Habersack, Angela; Wienecke, Miriam; Storch, Alexander; Reichmann, Heinz; Hummel, Thomas

2015-11-01

The effects of rasagiline on olfaction in animal studies are convincing. However, apart from various anecdotal patient reports, they could not be reproduced in prospective studies in humans. Cross-sectional data of large patient groups are still missing. The aim of this study was therefore to determine the olfactory function in a broad heterogeneous Parkinson's disease (PD) population with and without rasagiline intake. In this single-center, cross-sectional study 224 PD patients with and without rasagiline (1 mg/day) participated. Seventy-four of them received rasagiline as mono, or adjunct therapy. One-hundred fifty patients were untreated or received PD medication other than rasagiline. Comprehensive olfactory testing was performed for phenyl-ethyl alcohol odor thresholds, odor discrimination, and odor identification. Olfactory function did not differ between the two treatment groups with disease duration up to 29 years. Rasagiline-treated patients with disease duration of less than 8 years, however, presented with significant better odor discrimination abilities compared to PD patients without rasagiline treatment. This effect was no longer evident in patients with longer disease duration and proofed to be independent of age, sex, and medication. Our results may suggest that rasagiline treatment has a positive effect on the processing of olfactory information in early PD.

Decreased PD-1 expression on circulating CD4+T cell and PD-L1 expression on myeloid dendritic cell correlate with clinical manifestations in systemic juvenile idiopathic arthritis.

PubMed

Cai, Li; Zhang, Chenxing; Wu, Jing; Zhou, Wei; Chen, Tongxin

2018-03-30

Programmed cell death-1 (PD-1) and its ligand (PD-L1) mediate negative signal in autoimmune diseases. While little is known about its role in juvenile idiopathic arthritis (JIA). The study aimed to reveal the circulating cell profile and the relative PD-1/PD-L1 expression of JIA subsets, elucidating their underlying immunomodulatory mechanisms. We detected the circulating cells and the relative PD-1/PD-L1 signaling in 101 JIA patients and 50 controls by flow cytometry and analyzed their association with disease activity and clinical manifestations. Different from other JIA types, active systemic JIA (sJIA) patients had lower percentage and count of CD4 + T cells and lower PD-1 expression on them compared with healthy controls (P<0.05), active polyarthritis (P<0.05) and enthesitis-related arthritis (ERA) patients (P<0.05). Also, they had higher percentage and count of myeloid dendritic cell (mDC) and lower PD-L1 expression on mDC compared with healthy controls (P<0.05). Both PD-1 on CD4 + T cell and PD-L1 on mDC were negatively correlated with JADAS-27 in sJIA patients (P<0.05). In addition, PD-1 expression on CD4 + T cell was negatively associated with the number of involved joints (P<0.05) and PD-L1 on mDC was lower in patients with fever (P<0.01), which could further divide patients into two groups of different manifestations. Our finding displayed decreased CD4 + T cell, increased mDC and reduced PD-1/PD-L1 signal in sJIA PBMC comparing with other JIA subsets, which might be helpful in JIA differential diagnosis and responsible for distinct clinical manifestations via different mechanisms. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma.

PubMed

Chiu, Ying-Ming; Tsai, Chung-Lin; Kao, Jung-Ta; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Cheng, Ken-Sheng; Wu, Yi-Ying

2018-04-01

The programmed death 1 (PD-1) receptor and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of tumor infiltrating T lymphocytes in gastric adenocarcinoma patients are not well-defined. We characterized the expression of PD-1 and PD-L1 in peripheral blood and tumor infiltrating cells and analyzed the association between PD-1/PD-L1 expression and disease progression in a cohort of 60 patients with Helicobacter pylori infection, including 18 with gastric adenocarcinoma, 23 with gastritis, and 19 asymptomatic controls. Relative to controls, the expression of PD-1 on peripheral blood and tumor infiltrating T cells increased with disease progression. In vitro, T cells induced PD-L1 expression on primary gastric adenocarcinoma epithelial cells in an IFN-γ-dependent manner, which in turn promoted T cells apoptosis. Blocking of PD-L1 reversed this effect. This study provides evidence for a new therapeutic target in gastric adenocarcinoma patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

PubMed

Dirix, Luc Y; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E; Somer, Robert; Smakal, Martin; Emens, Leisha A; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja; Grote, Hans Juergen; Chin, Kevin; Hamilton, Erika P

2018-02-01

Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

Validation of a novel Montreal Cognitive Assessment scoring algorithm in non-demented Parkinson's disease patients.

PubMed

Sulzer, Patricia; Becker, Sara; Maetzler, Walter; Kalbe, Elke; van Nueten, Luc; Timmers, Maarten; Machetanz, Gerrit; Streffer, Johannes; Salvadore, Giacomo; Scholz, Erich; Tkaczynska, Zuzanna; Brockmann, Kathrin; Berg, Daniela; Liepelt-Scarfone, Inga

2018-06-23

The early diagnosis of mild cognitive impairment (PD-MCI) in Parkinson's disease (PD) is essential as it increases the future risk for PD dementia (PDD). Recently, a novel weighting algorithm for the Montreal Cognitive Assessment (MoCA) subtests has been reported, to best discriminate between those with and without cognitive impairment in PD. The aim of our study was to validate this scoring algorithm in a large sample of non-demented PD patients, hypothesizing that the weighted MoCA would have a higher diagnostic accuracy for PD-MCI than the original MoCA. In 202 non-demented PD patients, we evaluated cognitive status, clinical and demographic data, as well as the MoCA with a weighted and unweighted score. Receiver operating characteristic (ROC) curve analysis was used to evaluate discriminative ability of the MoCA. Group comparisons and ROC analysis were performed for PD-MCI classifications with a cut-off ≤ 1, 1.5, and 2 standard deviation (SD) below appropriate norms. PD-MCI patients scored lower on the weighted than the original MoCA version (p < 0.001) compared to PD patients with normal cognitive function. Areas under the curve only differed significantly for the 2 SD cut-off, leading to an increased sensitivity of the weighted MoCA score (72.9% vs. 70.5%) and specificity compared to the original version (79.0% vs. 65.4%). Our results indicate better discriminant power for the weighted MoCA compared to the original for more advanced stages of PD-MCI (2 SD cut-off). Future studies are needed to evaluate the predictive value of the weighted MoCA for PDD.

Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis.

PubMed

Zhuan-Sun, Yongxun; Huang, Fengting; Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng

2017-01-01

Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43-2.17, P <0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25-1.98, P =0.0001) and neural invasion (RR =1.30, 95% CI: 1.03-1.64, P =0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics.

Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis

PubMed Central

Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng

2017-01-01

Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43–2.17, P<0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25–1.98, P=0.0001) and neural invasion (RR =1.30, 95% CI: 1.03–1.64, P=0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics. PMID:29081663

G6PD as a predictive marker for glioma risk, prognosis and chemosensitivity.

PubMed

Yang, Chin-An; Huang, Hsi-Yuan; Lin, Cheng-Li; Chang, Jan-Gowth

2018-05-29

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme preventing cells from oxidative damage and has been reported to have tumor-promoting roles. This study aims to comprehensively evaluate the predictive values of G6PD on brain tumor risk, prognosis and chemo-resistance. A retrospective 13-year cohort study analyzing cancer risk using the Taiwan National Health Insurance Research Database (4066 G6PD deficiency patients and 16,264 controls) was conducted. Furthermore, RNAseq and clinical data of grade II-III glioma (LGG, n = 515) and glioblastoma (GBM, n = 155) were downloaded from The Cancer Genome Atlas (TCGA) and analyzed. Bioinformatics methods were applied to build a glioma prognostication model and to predict response to chemotherapy based on tumor G6PD-related gene expressions. The predicted results were validated in another glioma cohort GSE 16011 and in KALS1 cell line. G6PD-dificient patients were found to have an increased risk for cancers, especially for brain tumor (adjusted hazard ratio (HR) 10.5, 95% CI 1.03-7.60). Furthermore, higher tumor G6PD expression was associated with poor patient survival in LGG, but not in GBM. A prognostication model using expression levels of G6PD and 9 related genes (PSMA2, PSMB8, SHFM1, GSS, GSTK1, MGST2, POLD3, MSH2, MSH6) could independently predict LGG patient survival. Boosted decision tree analysis on 213 cancer cell line database revealed predictive values of G6PD expression on response to gemcitabine and bortezomib. Knockdown of G6PD in KALS1 cell line enhanced its sensitivity to both chemotherapeutic agents. Our study suggests that G6PD could be a marker predicting glioma risk, prognosis and chemo-sensitivity.

Fluid Status in Peritoneal Dialysis Patients: The European Body Composition Monitoring (EuroBCM) Study Cohort

PubMed Central

Van Biesen, Wim; Williams, John D.; Covic, Adrian C.; Fan, Stanley; Claes, Kathleen; Lichodziejewska-Niemierko, Monika; Verger, Christian; Steiger, Jurg; Schoder, Volker; Wabel, Peter; Gauly, Adelheid; Himmele, Rainer

2011-01-01

Background Euvolemia is an important adequacy parameter in peritoneal dialysis (PD) patients. However, accurate tools to evaluate volume status in clinical practice and data on volume status in PD patients as compared to healthy population, and the associated factors, have not been available so far. Methods We used a bio-impedance spectroscopy device, the Body Composition Monitor (BCM) to assess volume status in a cross-sectional cohort of prevalent PD patients in different European countries. The results were compared to an age and gender matched healthy population. Results Only 40% out of 639 patients from 28 centres in 6 countries were normovolemic. Severe fluid overload was present in 25.2%. There was a wide scatter in the relation between blood pressure and volume status. In a multivariate analysis in the subgroup of patients from countries with unrestricted availability of all PD modalities and fluid types, older age, male gender, lower serum albumin, lower BMI, diabetes, higher systolic blood pressure, and use of at least one exchange per day with the highest hypertonic glucose were associated with higher relative tissue hydration. Neither urinary output nor ultrafiltration, PD fluid type or PD modality were retained in the model (total R2 of the model = 0.57). Conclusions The EuroBCM study demonstrates some interesting issues regarding volume status in PD. As in HD patients, hypervolemia is a frequent condition in PD patients and blood pressure can be a misleading clinical tool to evaluate volume status. To monitor fluid balance, not only fluid output but also dietary input should be considered. Close monitoring of volume status, a correct dialysis prescription adapted to the needs of the patient and dietary measures seem to be warranted to avoid hypervolemia. PMID:21390320

[Increased expressions of peripheral PD-1+ lymphocytes and CD4+CD25+FOXP3+ T cells in gastric adenocarcinoma patients].

PubMed

Li, Hao; Li, Songyan; Hu, Shidong; Zou, Guijun; Hu, Zilong; Wei, Huahua; Wang, Yufeng; Du, Xiaohui

2017-01-01

Objective To detect the frequencies of peripheral programmed death-1 + (PD-1 + ) lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in patients with gastric adenocarcinoma. Methods The study enrolled 29 patients with gastric adenocarcinoma and 29 age- and sex-matched healthy controls. Frequencies of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells were detected using flow cytometry. Results The number of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood was higher in patients with gastric adenocarcinoma than that in the control group. Moreover, linear correlation analysis indicated a positive correlation between PD-1 expression and frequency of CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood of the patients. Conclusion Gastric adenocarcinoma patients present with increased PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in the peripheral blood.

Features of GBA-associated Parkinson's disease at presentation in the UK Tracking Parkinson's study.

PubMed

Malek, Naveed; Weil, Rimona S; Bresner, Catherine; Lawton, Michael A; Grosset, Katherine A; Tan, Manuela; Bajaj, Nin; Barker, Roger A; Burn, David J; Foltynie, Thomas; Hardy, John; Wood, Nicholas W; Ben-Shlomo, Yoav; Williams, Nigel W; Grosset, Donald G; Morris, Huw R

2018-01-29

To examine the influence of the glucocerebrosidase ( GBA ) mutation carrier state on age at onset of Parkinson's disease (PD), the motor phenotype and cognitive function at baseline assessment in a large cohort of UK patients. We also analysed the prevalence of mood and behavioural problems that may confound the assessment of cognitive function. We prospectively recruited patients with PD in the Tracking Parkinson's study. We fully sequenced the GBA gene in all recently diagnosed patients (≤3.5 years). We examined cognitive (Montreal Cognitive Assessment) and motor (Movement Disorder Society Unified Parkinson's Disease Rating Scale part 3) function at a baseline assessment, at an average of 1.3 years after diagnosis. We used logistic regression to determine predictors of PD with mild cognitive impairment and PD with dementia. We studied 1893 patients with PD: 48 (2.5%) were heterozygous carriers for known Gaucher's disease (GD) causing pathogenic mutations; 117 (6.2%) had non-synonymous variants, previously associated with PD, and 28 (1.5%) patients carried variants of unknown significance in the GBA gene. L444P was the most common pathogenic GBA mutation. Patients with pathogenic GBA mutations were on average 5 years younger at disease onset compared with non-carriers (P=0.02). PD patients with GD-causing mutations did not have an increased family risk of PD. Patients with GBA mutations were more likely to present with the postural instability gait difficulty phenotype compared with non-carriers (P=0.02). Patients carrying pathogenic mutations in GBA had more advanced Hoehn and Yahr stage after adjustment for age and disease duration compared with non-carriers (P=0.005). There were no differences in cognitive function between GBA mutation carriers and non-carriers at this early disease stage. Our study confirms the influence of GBA mutations on the age of onset, disease severity and motor phenotype in patients with PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline, implying that cognitive impairment/dementia, reported in other studies at a later disease stage, is not present in recently diagnosed cases. This offers an important window of opportunity for potential disease-modifying therapy that may protect against the development of dementia in GBA -PD. NCT02881099; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

White matter integrity and cognition in Parkinson's disease: a cross-sectional study

PubMed Central

Auning, Eirik; Kjærvik, Veslemøy Krohn; Selnes, Per; Aarsland, Dag; Haram, Astrid; Bjørnerud, Atle; Hessen, Erik; Esnaashari, Abdolreza; Fladby, Tormod

2014-01-01

Objective We used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinson’s disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimer’s disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance. Methods This study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group. Results Patients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities. Conclusions In early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD. PMID:24448846

Compulsive behaviors in patients with Parkinson's disease.

PubMed

Kenangil, Gülay; Ozekmekçi, Sibel; Sohtaoglu, Melis; Erginöz, Ethem

2010-05-01

Several impulse control disorders (ICDs) may develop in patients with Parkinson's disease (PD). We aimed to identify the frequency and phenomenology of ICDs in our PD population. Among 554 PD patients examined in a 3-year period, we identified 33 patients with ICDs. Disease duration, gender, and age-matched 65 PD patients without ICDs were selected as controls. We noted age-at-onset, duration, and severity of PD, dose and types of dopaminergic treatment, as well as presence of motor complications in both groups. Of 554 patients, 33 (5.9%) had ICDs, of whom, 27 were men (81%), mean age-at onset of PD was 48 and disease duration 8 years. While all patients with ICDs were on dopamine agonist drugs (+/- an adjuvant), all but 2 of controls were on dopamine agonists. Punding was the most frequent behavioral problem (57%), 42% exhibited aggressive hypersexuality, 27% compulsive eating, 24% pathologic shopping, and 21% compulsive medication. Severity of PD, presence of l-Dopa-induced motor complications, l-Dopa equivalent doses of dopamine agonists administered were not statistically different between 2 groups. In this study performed in a tertiary clinic for movement disorders in Turkey, several ICDs occurred in a small group of PD patients, mostly in men with young-onset disease, similar to the previous reported series. However, in contrast to the Western series, the number of gamblers was quite low because gambling is illegal in our country. We did not find any association between ICDs and severity of PD as well as doses of dopaminergic agents.

Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer.

PubMed

Cho, Jong Ho; Zhou, Wei; Choi, Yoon-La; Sun, Jong-Mu; Choi, Hyejoo; Kim, Tae-Eun; Dolled-Filhart, Marisa; Emancipator, Kenneth; Rutkowski, Mary Anne; Kim, Jhingook

2018-01-01

Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor ( EGFR )-mutant non-small cell lung cancer (NSCLC). We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR -mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis. All patients had ≥1 EGFR mutation-54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1-positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1-positive groups (TPS ≥ 1%) compared with the PD-L1-negative group (median, 35 months). PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR -mutant NSCLC.

Effects of Personality Disorders on Functioning and Well-Being in Major Depressive Disorder

PubMed Central

SKODOL, ANDREW E.; GRILO, CARLOS M.; PAGANO, MARIA E.; BENDER, DONNA S.; GUNDERSON, JOHN G.; SHEA, M. TRACIE; YEN, SHIRLEY; ZANARINI, MARY C.; MCGLASHAN, THOMAS H.

2008-01-01

Background Patients with depressive disorders have limitations in physical and emotional functioning comparable to patients with chronic medical conditions. Personality disorders (PDs) are also known to be associated with functional impairment. Aims To determine the effects of PDs on the functioning and well-being of patients with major depressive disorder (MDD). Method In the Collaborative Longitudinal Personality Disorders Study, 668 patients who met criteria for schizotypal, borderline, avoidant, or obsessive-compulsive PDs or for MDD and no PD were assessed with semi-structured interviews at baseline, 6, 12, 24, and 36 months. In this study, 151 patients who met criteria for current MDD at the 36-month follow-up were compared on the basis of the presence (n = 118) or absence (n = 33) of persistent PD. Physical and social/emotional functioning and well-being were assessed using the Medical Outcomes Study (MOS) Short-Form Health Survey (SF-36). These results were compared with those of a sample of patients with MDD seen in the mental health specialty sector who were followed in the Medical Outcomes Study. Results Patients with MDD and co-occurring PD had significantly more impairment on scales measuring role limitations due to emotional problems, social functioning, and general health perceptions than patients with MDD and no PD. Although patients with MDD and no PD were found to have levels of functioning and well-being that were lower in several domains than those previously reported in depressed patients recruited from mental health settings, patients with MDD and co-occurring PD were found to have much lower levels of functioning in all areas than reported samples. Conclusions Co-occurring PDs contribute significantly to impairment in social and emotional functioning and reduced well-being in patients with MDD. PMID:16304504

Associations between serotonin-related gene polymorphisms and panic disorder.

PubMed

Maron, Eduard; Lang, Aavo; Tasa, Gunnar; Liivlaid, Liivi; Tõru, Innar; Must, Anne; Vasar, Veiko; Shlik, Jakov

2005-06-01

Studies suggest that vulnerability to panic attacks and panic disorder (PD) may be related to a deficient serotonin (5-HT) neurotransmission. In the present case-control study we investigated possible associations between PD phenotype and five candidate polymorphisms including 5-HT transporter (5-HTTLPR and VNTR), monoamine oxidase A (MAOA promoter region), tryptophan hydroxylase 1 (TPH1 218A/C) and 5-HT1B receptor (5-HT1BR 861G/C) genes. The study sample consisted of 158 patients with PD and 215 healthy control subjects. The analysis showed higher frequencies of LL genotype (p = 0.016) and L allele variant (p = 0.007) of 5-HTTLPR in the patients. No significant associations were observed between PD and other candidate gene polymorphisms. However, a higher frequency of longer allele genotypes of the MAOA promoter region was observed in female PD patients with agoraphobia than in female controls (p = 0.016). These findings indicate that genetic variants conceivably related to lower 5-HT neurotransmission may be involved in the development of PD.

The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease

PubMed Central

Gan-Or, Ziv; Ozelius, Laurie J.; Bar-Shira, Anat; Saunders-Pullman, Rachel; Mirelman, Anat; Kornreich, Ruth; Gana-Weisz, Mali; Raymond, Deborah; Rozenkrantz, Liron; Deik, Andres; Gurevich, Tanya; Gross, Susan J.; Schreiber-Agus, Nicole; Giladi, Nir; Bressman, Susan B.

2013-01-01

Objective: To study the possible association of founder mutations in the lysosomal storage disorder genes HEXA, SMPD1, and MCOLN1 (causing Tay-Sachs, Niemann-Pick A, and mucolipidosis type IV diseases, respectively) with Parkinson disease (PD). Methods: Two PD patient cohorts of Ashkenazi Jewish (AJ) ancestry, that included a total of 938 patients, were studied: a cohort of 654 patients from Tel Aviv, and a replication cohort of 284 patients from New York. Eight AJ founder mutations in the HEXA, SMPD1, and MCOLN1 genes were analyzed. The frequencies of these mutations were compared to AJ control groups that included large published groups undergoing prenatal screening and 282 individuals matched for age and sex. Results: Mutation frequencies were similar in the 2 groups of patients with PD. The SMPD1 p.L302P was strongly associated with a highly increased risk for PD (odds ratio 9.4, 95% confidence interval 3.9–22.8, p < 0.0001), as 9/938 patients with PD were carriers of this mutation compared to only 11/10,709 controls. Conclusions: The SMPD1 p.L302P mutation is a novel risk factor for PD. Although it is rare on a population level, the identification of this mutation as a strong risk factor for PD may further elucidate PD pathogenesis and the role of lysosomal pathways in disease development. PMID:23535491

Abnormal Echogenicity of the Substantia Nigra, Raphe Nuclei, and Third-Ventricle Width as Markers of Cognitive Impairment in Parkinsonian Disorders: A Cross-Sectional Study

PubMed Central

Bouwmans, Angela E. P.; Leentjens, Albert F. G.; Mess, Werner H.; Weber, Wim E. J.

2016-01-01

Background. Patients with Parkinson's disease (PD) have a high risk of cognitive problems. Objective. This study assesses whether abnormal echogenicity of the substantia nigra (SN) and raphe nuclei (RN) and the diameter of third ventricle are markers of cognitive impairment in patients with PD and other forms of parkinsonism. Methods. 126 outpatients with early signs of parkinsonism underwent transcranial sonography (TCS). The scales for the outcome of Parkinson's disease cognition (SCOPA-COG) were used as cognitive measure. Definite neurological diagnosis was established after two-year follow-up. Results. One-third of the patients with PD and half of those with APS had signs of cognitive impairment. The echogenicity of the SN was not related to cognitive impairment. The diameter of the third ventricle was significantly larger in PD patients with cognitive impairment compared to those without. In patients with APS we found a significantly higher frequency of hypoechogenic RN in patients with cognitive problems. Conclusions. Cognitive impairment is already present in a substantial proportion of patients with PD and APS at first referral. In patients with APS the frequency of hypoechogenic RN points to the direction of other pathophysiology with more emphasis on deficits in the serotonergic neurotransmitter system. The larger diameter of the third ventricle in PD patients with cognitive impairment may reflect Alzheimer like brain atrophy, as has been reported in earlier studies. PMID:26881179

Cognitive training in Parkinson disease: cognition-specific vs nonspecific computer training.

PubMed

Zimmermann, Ronan; Gschwandtner, Ute; Benz, Nina; Hatz, Florian; Schindler, Christian; Taub, Ethan; Fuhr, Peter

2014-04-08

In this study, we compared a cognition-specific computer-based cognitive training program with a motion-controlled computer sports game that is not cognition-specific for their ability to enhance cognitive performance in various cognitive domains in patients with Parkinson disease (PD). Patients with PD were trained with either a computer program designed to enhance cognition (CogniPlus, 19 patients) or a computer sports game with motion-capturing controllers (Nintendo Wii, 20 patients). The effect of training in 5 cognitive domains was measured by neuropsychological testing at baseline and after training. Group differences over all variables were assessed with multivariate analysis of variance, and group differences in single variables were assessed with 95% confidence intervals of mean difference. The groups were similar regarding age, sex, and educational level. Patients with PD who were trained with Wii for 4 weeks performed better in attention (95% confidence interval: -1.49 to -0.11) than patients trained with CogniPlus. In our study, patients with PD derived at least the same degree of cognitive benefit from non-cognition-specific training involving movement as from cognition-specific computerized training. For patients with PD, game consoles may be a less expensive and more entertaining alternative to computer programs specifically designed for cognitive training. This study provides Class III evidence that, in patients with PD, cognition-specific computer-based training is not superior to a motion-controlled computer game in improving cognitive performance.

Subjective Cognitive Complaints and Objective Cognitive Impairment in Parkinson's Disease.

PubMed

Hong, Jin Yong; Lee, Yoonju; Sunwoo, Mun Kyung; Sohn, Young H; Lee, Phil Hyu

2018-01-01

Subjective cognitive complaints (SCCs) are very common in patients with Parkinson's disease (PD). However, the relationship between SCCs and objective cognitive impairment is still unclear. This study aimed to determine whether SCCs are correlated with objective cognitive performance in patients with PD. Totals of 148 cognitively normal patients, 71 patients with mild cognitive impairment (MCI), and 31 demented patients were recruited consecutively from a movement-disorders clinic. Their SCCs and cognitive performances were evaluated using the Cognitive Complaints Interview (CCI) and a comprehensive neuropsychological battery. The CCI score increased with age, duration of PD, and depression score, and was inversely correlated with cognitive performance. The association between CCI score and performance remained significant after adjustment for the depression score, age, and duration of PD. The CCI score could be used to discriminate patients with dementia from cognitively normal and MCI patients [area under the receiver operating characteristics curve (AUC) of 0.80], but not patients with MCI or dementia from cognitively normal patients (AUC of 0.67). SCCs as measured by the CCI are strongly correlated with objective cognitive performance in patients with PD. The CCI can also be used to screen for dementia in patients with PD. Copyright © 2018 Korean Neurological Association.

Verbal Fluency Performance in Patients with Non-demented Parkinson's Disease

PubMed Central

Khatoonabadi, Ahmad Reza; Bakhtiyari, Jalal

2013-01-01

Objective While Parkinson's disease (PD) has traditionally been defined by motor symptoms, many researches have indicated that mild cognitive impairment is common in non-demented PD patients. The purpose of this study was to compare verbal fluency performance in non-demented Parkinson's disease patients with healthy controls. Method In this cross-sectional study thirty non-demented Parkinson's disease patients and 30 healthy controls, matched by age, gender and education, were compared on verbal fluency performance. Verbal fluency was studied with a Phonemic Fluency task using the letters F, A, and S, a semantic fluency task using the categories animals and fruits. The independent t-test was used for data analysis. Results Overall, participants generated more words in the semantic fluency task than in the phonemic fluency task. Results revealed significant differences between patients and controls in semantic fluency task (p<.05). In addition, PD patients showed a significant reduction of correctly generated words in letter fluency task. The total number of words produced was also significantly lower in the PD group (p<.05). Conclusion Verbal fluency disruption is implied in non-demented PD patients in association with incipient cognitive impairment. PMID:23682253

Compliance, normality, and the patient on peritoneal dialysis.

PubMed

McCarthy, Alexandra; Shaban, Ramon; Boys, Jennifer; Winch, Sarah

2010-01-01

Monitoring and enhancing patient compliance with peritoneal dialysis (PD) is a recurring and problematic theme in the renal literature. A growing body of literature also argues that a failure to understand the patient's perspective of compliance may be contributing to these problems. The aim of this study was to understand the concept of compliance with PD from the patient's perspective. Using the case study approach recommended by Stake (1995), five patients on PD consented to in-depth interviews that explored the meaning of compliance in the context of PD treatment and lifestyle regimens recommended by health professionals. Participants also discussed factors that influenced their choices to follow, disregard, or refine these regimens. Results indicate that health professionals acting in alignment with individual patient needs and wishes, and demonstrating an awareness of the constraints under which patients operate and the strengths they bring to their treatment, may be the most significant issues to consider with respect to definitions of PD compliance and the development of related compliance interventions. Aspects of compliance that promoted relative normality were also important to the participants in this study and tended to result in greater concordance with health professionals' advice.

Effects of Rotigotine on REM Sleep Behavior Disorder in Parkinson Disease.

PubMed

Wang, Yan; Yang, Yuechang; Wu, Huijuan; Lan, Danmei; Chen, Ying; Zhao, Zhongxin

2016-10-15

REM sleep behavior disorder (RBD) is a common manifestation of Parkinson disease (PD). In this study, we assessed the effects of rotigotine transdermal patch on RBD features in patients with PD. In this prospective open-label study, eleven PD patients with untreated RBD were administered rotigotine patches for up to seven months to ameliorate their parkinsonism. The severities of their RBD symptoms before and after rotigotine therapy were evaluated through patient and bed partner interviews, a validated evaluation scale (REM sleep behavior disorder questionnaire-Hong Kong, RBDQ-HK), and blinded assessments based on video-polysomnographic (VPSG) measure. Rotigotine improved parkinsonism and subjective sleep quality in PD patients with RBD. The RBDQ-HK total score, especially the Factor 2 score, was decreased, which demonstrated that the subjective severity of RBD symptoms was improved after rotigotine treatment, especially the frequency and severity of abnormal RBD-related motor behaviors. The VPSG analyses showed that the total sleep time (TST) and stage 1% were increased and that the PLMS index was decreased. However, no differences in the RBD-related sleep measures were observed. The improved RBD symptoms and VPSG measures of PD patients in this study (TST, stage 1%, and PLMS index) suggest that, in PD, rotigotine may partially improve RBD-related symptoms. Rotigotine should be considered to be an optional drug for the treatment of RBD symptoms in PD. © 2016 American Academy of Sleep Medicine

Chocolate consumption is increased in Parkinson's disease. Results from a self-questionnaire study.

PubMed

Wolz, Martin; Kaminsky, Alice; Löhle, Matthias; Koch, Rainer; Storch, Alexander; Reichmann, Heinz

2009-03-01

Clinical observations in Parkinson's disease (PD) patients suggested an increased chocolate consumption. Chocolate contains high contents of various biogenic amines potentially influencing brain monoamine metabolism. 498 PD patients and their partners were evaluated by a structured self-questionnaire asking for consumption of chocolate and non-chocolate sweets, changes in chocolate consumption during the disease course, and depressive symptoms. Questionnaires from 274 patients (55 %) and 234 controls were eligible for further analysis. Consumption of chocolate was significantly higher in PD patients compared to controls, while consumption of non-chocolate sweets was similar in both groups. Our study suggests that chocolate consumption is increased in PD independent of concomitant depressive symptoms measured by BDI-1. Although reasons for increased chocolate consumption in PD remain elusive, it may hypothetically be a consequence of the high content of various biogenic amines and/or caffeine analogues with potential antiparkinsonian effects.

Hemodialysis versus Peritoneal Dialysis: A Comparison of Survival Outcomes in South-East Asian Patients with End-Stage Renal Disease.

PubMed

Yang, Fan; Khin, Lay-Wai; Lau, Titus; Chua, Horng-Ruey; Vathsala, A; Lee, Evan; Luo, Nan

2015-01-01

Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from South-East Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore. Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease. After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p<0.001), although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28, p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (≤65 years old) without diabetes or cardiovascular disease. ESRD patients who initiated dialysis with HD experienced better survival outcomes than those who initiated dialysis with PD in Singapore, although survival outcomes may not differ between the two dialysis modalities in young and healthier patients. These findings are potentially confounded by selection bias, as patients were not randomized to the two dialysis modalities in this cohort study.

Serum Alkaline Phosphatase Levels Predict Infection-Related Mortality and Hospitalization in Peritoneal Dialysis Patients.

PubMed

Hwang, Seun Deuk; Kim, Su-Hyun; Kim, Young Ok; Jin, Dong Chan; Song, Ho Chul; Choi, Euy Jin; Kim, Yong-Lim; Kim, Yon-Su; Kang, Shin-Wook; Kim, Nam-Ho; Yang, Chul Woo; Kim, Yong Kyun

2016-01-01

Serum alkaline phosphatase (ALP) levels have been reported to be associated with all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients. However, it is unclear whether serum ALP levels predict infection-related clinical outcomes in PD patients. The aim of this study was to determine the relationships between serum ALP levels, infection-related mortality and hospitalization in PD patients. PD patients from the Clinical Research Center registry for end-stage renal disease, a multicenter prospective observational cohort study in Korea, were included in the present study. Patients were categorized into three groups by serum ALP tertiles as follows: Tertile 1, ALP <78 U/L; Tertile 2, ALP = 78-155 U/L; Tertile 3, ALP >155 U/L. Tertile 1 was used as the reference category. The primary outcomes were infection-related mortality and hospitalization. A total of 1,455 PD patients were included. The median follow-up period was 32 months. The most common cause of infection-related mortality and hospitalization was PD-related peritonitis. Multivariate Cox regression analyses showed that patients in the highest tertiles of serum ALP levels were at higher risk of infection-related mortality (HR 2.29, 95% CI, 1.42-5.21, P = 0.008) after adjustment for clinical variables. Higher tertiles of serum ALP levels were associated with higher risk of infection-related hospitalization (Tertile 2: HR 1.56, 95% CI, 1.18-2.19, P = 0.009, tertile 3: HR 1.34, 95% CI, 1.03-2.62, P = 0.031). Our data showed that elevated serum ALP levels were independently associated with a higher risk of infection-related mortality and hospitalization in PD patients.

Virtual multiple errands test (VMET): a virtual reality-based tool to detect early executive functions deficit in Parkinson’s disease

PubMed Central

Cipresso, Pietro; Albani, Giovanni; Serino, Silvia; Pedroli, Elisa; Pallavicini, Federica; Mauro, Alessandro; Riva, Giuseppe

2014-01-01

Introduction: Several recent studies have pointed out that early impairment of executive functions (EFs) in Parkinson’s Disease (PD) may be a crucial marker to detect patients at risk for developing dementia. The main objective of this study was to compare the performances of PD patients with mild cognitive impairment (PD-MCI) with PD patients with normal cognition (PD-NC) and a control group (CG) using a traditional assessment of EFs and the Virtual Multiple Errands Test (VMET), a virtual reality (VR)-based tool. In order to understand which subcomponents of EFs are early impaired, this experimental study aimed to investigate specifically which instrument best discriminates among these three groups. Materials and methods: The study included three groups of 15 individuals each (for a total of 45 participants): 15 PD-NC; 15 PD-MCI, and 15 cognitively healthy individuals (CG). To assess the global neuropsychological functioning and the EFs, several tests (including the Mini Mental State Examination (MMSE), Clock Drawing Test, and Tower of London test) were administered to the participants. The VMET was used for a more ecologically valid neuropsychological evaluation of EFs. Results: Findings revealed significant differences in the VMET scores between the PD-NC patients vs. the controls. In particular, patients made more errors in the tasks of the VMET, and showed a poorer ability to use effective strategies to complete the tasks. This VMET result seems to be more sensitive in the early detection of executive deficits because these two groups did not differ in the traditional assessment of EFs (neuropsychological battery). Conclusion: This study offers initial evidence that a more ecologically valid evaluation of EFs is more likely to lead to detection of subtle executive deficits. PMID:25538578

Virtual multiple errands test (VMET): a virtual reality-based tool to detect early executive functions deficit in Parkinson's disease.

PubMed

Cipresso, Pietro; Albani, Giovanni; Serino, Silvia; Pedroli, Elisa; Pallavicini, Federica; Mauro, Alessandro; Riva, Giuseppe

2014-01-01

Several recent studies have pointed out that early impairment of executive functions (EFs) in Parkinson's Disease (PD) may be a crucial marker to detect patients at risk for developing dementia. The main objective of this study was to compare the performances of PD patients with mild cognitive impairment (PD-MCI) with PD patients with normal cognition (PD-NC) and a control group (CG) using a traditional assessment of EFs and the Virtual Multiple Errands Test (VMET), a virtual reality (VR)-based tool. In order to understand which subcomponents of EFs are early impaired, this experimental study aimed to investigate specifically which instrument best discriminates among these three groups. The study included three groups of 15 individuals each (for a total of 45 participants): 15 PD-NC; 15 PD-MCI, and 15 cognitively healthy individuals (CG). To assess the global neuropsychological functioning and the EFs, several tests (including the Mini Mental State Examination (MMSE), Clock Drawing Test, and Tower of London test) were administered to the participants. The VMET was used for a more ecologically valid neuropsychological evaluation of EFs. Findings revealed significant differences in the VMET scores between the PD-NC patients vs. the controls. In particular, patients made more errors in the tasks of the VMET, and showed a poorer ability to use effective strategies to complete the tasks. This VMET result seems to be more sensitive in the early detection of executive deficits because these two groups did not differ in the traditional assessment of EFs (neuropsychological battery). This study offers initial evidence that a more ecologically valid evaluation of EFs is more likely to lead to detection of subtle executive deficits.

Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort.

PubMed

Hwang, Shelley Ji Eun; Carlos, Giuliana; Wakade, Deepal; Byth, Karen; Kong, Benjamin Y; Chou, Shaun; Carlino, Matteo S; Kefford, Richard; Fernandez-Penas, Pablo

2016-03-01

Anti-programmed cell death (PD)-1 therapy is emerging as the backbone of new standard of care immunotherapy for metastatic melanoma. Immune-related cutaneous events are observed in these patients. We sought to describe cutaneous adverse events observed in patients with metastatic melanoma on anti-PD-1 therapy. We reviewed the clinical and histologic information of all patients treated with single-agent anti-PD-1 therapy for metastatic melanoma at Westmead Hospital, Sydney, Australia, from May 2012 to February 2015. Of the 82 patients included in the study, 34 had dermatology assessments. Forty (49%) developed a form of anti-PD-1-associated cutaneous adverse events. In all, 17% developed lichenoid reactions and eczema, and 15% developed vitiligo. An estimated 25% of patients were expected to develop their first lichenoid reactions within 8.3 months, and eczema and vitiligo within 10.3 months of therapy. These adverse events tend to appear together in patients on anti-PD-1 therapy. The study was from a single center and clinical information was reviewed retrospectively in patients not referred to dermatology. Anti-PD-1 therapy is associated with the development of immune-related cutaneous events. Lichenoid reactions, eczema, and vitiligo are the 3 most prevalent lesions observed in our population. There is a tendency for lichenoid reactions and eczema to occur with vitiligo. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Spontaneous Swallowing during All-Night Sleep in Patients with Parkinson Disease in Comparison with Healthy Control Subjects.

PubMed

Uludag, Irem Fatma; Tiftikcioglu, Bedile Irem; Ertekin, Cumhur

2016-04-01

Spontaneous saliva swallows (SS) appear especially during sleep. The rate of SS was rarely investigated in all-night sleep in patients with Parkinson disease (PD). Dysphagia is a frequent symptom in PD, but the rate of SS was never studied with an all-night sleep electroencephalogram (EEG). A total of 21 patients with PD and 18 age-matched healthy controls were included in the study. Frequencies of SS and coughing were studied in all-night sleep recordings of patients with PD and controls. During all-night sleep, video-EEG 12-channel recording was used including the electromyography (EMG) of the swallowing muscles, nasal airflow, and recording of vertical laryngeal movement using a pair of EEG electrodes over the thyroid cartilage. The total number of SS was increased while the mean duration of sleep was decreased in PD when compared to controls. Sialorrhea and clinical dysphagia, assessed by proper questionnaires, had no effect in any patient group. The new finding was the so-called salvo type of consecutive SS in one set of swallowing. The amount of coughing was significantly increased just after the salvo SS. In PD, the rate of SS was not sufficient to demonstrate the swallowing disorder, such as oropharyngeal dysphagia, but the salvo type of SS was quite frequent. This is a novel finding and may contribute to the understanding of swallowing problems in patients with dysphagic or nondysphagic PD. © 2016 Associated Professional Sleep Societies, LLC.

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

PubMed Central

Kwon, Ji Eun; Koh, Seong-Joon; Chun, Jaeyoung; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae

2014-01-01

AIM: To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients. METHODS: This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms. RESULTS: Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients. CONCLUSION: The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis. PMID:25057226

Non-Motor Symptom Burdens Are Not Associated with Iron Accumulation in Early Parkinson's Disease: a Quantitative Susceptibility Mapping Study.

PubMed

Shin, Chaewon; Lee, Seon; Lee, Jee Young; Rhim, Jung Hyo; Park, Sun Won

2018-03-26

Quantitative susceptibility mapping (QSM) has been used to measure iron accumulation in the deep nuclei of patients with Parkinson's disease (PD). This study examined the relationship between non-motor symptoms (NMSs) and iron accumulation in the deep nuclei of patients with PD. The QSM data were acquired from 3-Tesla magnetic resonance imaging (MRI) in 29 patients with early PD and 19 normal controls. The Korean version of the NMS scale (K-NMSS) was used for evaluation of NMSs in patients. The patients were divided into high NMS and low NMS groups. The region-of-interest analyses were performed in the following deep nuclei: red nucleus, substantia nigra pars compacta, substantia nigra pars reticulata, dentate nucleus, globus pallidus, putamen, and head of the caudate nucleus. Thirteen patients had high NMS scores (total K-NMSS score, mean = 32.1), and 16 had low NMS scores (10.6). The QSM values in the deep were not different among the patients with high NMS scores, low NMS scores, and controls. The QSM values were not correlated linearly with K-NMSS total score after adjusting the age at acquisition of brain MRI. The study demonstrated that the NMS burdens are not associated with iron accumulation in the deep nuclei of patients with PD. These results suggest that future neuroimaging studies on the pathology of NMSs in PD should use more specific and detailed clinical tools and recruit PD patients with severe NMSs. © 2018 The Korean Academy of Medical Sciences.

Assessment of current practice and barriers to antimicrobial prophylaxis in peritoneal dialysis patients.

PubMed

Campbell, Denise J; Brown, Fiona G; Craig, Jonathan C; Gallagher, Martin P; Johnson, David W; Kirkland, Geoffrey S; Kumar, Subramanian K; Lim, Wai H; Ranganathan, Dwarakanathan; Saweirs, Walaa; Sud, Kamal; Toussaint, Nigel D; Walker, Rowan G; Williams, Lesley A; Yehia, Maha; Mudge, David W

2016-04-01

Existing Australasian and international guidelines outline antibiotic and antifungal measures to prevent the development of treatment-related infection in peritoneal dialysis (PD) patients. Practice patterns and rates of PD-related infection vary widely across renal units in Australia and New Zealand and are known to vary significantly from guideline recommendations, resulting in PD technique survival rates that are lower than those achieved in many other countries. The aim of this study was to determine if there is an association between current practice and PD-related infection outcomes and to identify the barriers and enablers to good clinical practice. This is a multicentre network study involving eight PD units in Australia and New Zealand, with a focus on adherence to guideline recommendations on antimicrobial prophylaxis in PD patients. Current practice was established by asking the PD unit heads to respond to a short survey about practice/protocols/policies and a 'process map' was constructed following a face-to-face interview with the primary PD nurse at each unit. The perceived barriers/enablers to adherence to the relevant guideline recommendations were obtained from the completion of 'cause and effect' diagrams by the nephrologist and PD nurse at each unit. Data on PD-related infections were obtained for the period 1 January 2011 to 31 December 2011. Perceived barriers that may result in reduced adherence to guideline recommendations included lack of knowledge, procedural lapses, lack of a centralized patient database, patients with non-English speaking background, professional concern about antibiotic resistance, medication cost and the inability of nephrologists and infectious diseases staff to reach consensus on unit protocols. The definitions of PD-related infections used by some units varied from those recommended by the International Society for Peritoneal Dialysis, particularly with exit-site infection (ESI). Wide variations were observed in the rates of ESI (0.06-0.53 episodes per patient-year) and peritonitis (0.31-0.86 episodes per patient-year). Despite the existence of strongly evidence-based guideline recommendations, there was wide variation in adherence to these recommendations between PD units which might contribute to PD-related infection rates, which varied widely between units. Although individual patient characteristics may account for some of this variability, inconsistencies in the processes of care to prevent infection in PD patients also play a role. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Anxiety in early Parkinson's disease: Validation of the Italian observer-rated version of the Parkinson Anxiety Scale (OR-PAS).

PubMed

Santangelo, Gabriella; Falco, Fabrizia; D'Iorio, Alfonsina; Cuoco, Sofia; Raimo, Simona; Amboni, Marianna; Pellecchia, Maria Teresa; Longo, Katia; Vitale, Carmine; Barone, Paolo

2016-08-15

Anxiety disorders are common in Parkinson's Disease (PD) and their identification is relevant even at early stages. The Parkinson Anxiety Scale (PAS) evaluates anxiety in PD; it was used only in the original validation study in PD patients mainly at 2-3 stages of Hoehn & Yahr system (H&Y). The study aimed to investigate psychometric properties of observer-rated version of the PAS (OR-PAS), prevalence rate of anxiety and its features, compared with diagnostic criteria in early PD patients. A sample of 101 PD patients with H&Y:1-2 underwent the OR-PAS. To assess convergent and divergent validity, PD patients underwent Beck Anxiety Inventory, and scales assessing depression, apathy, anhedonia and cognition. To diagnose anxiety disorders, Mini International Neuropsychiatric Inventory was used as gold standard. A "receiver operating characteristics" curve was obtained; positive and negative predictive values were calculated for different cut-off points of the OR-PAS and its subscales. There was no missing data, no floor and ceiling effects; mean score was 12.2±10.1; Cronbach's alpha was 0.899. The OR-PAS showed good convergent and divergent validity. Maximum discrimination was obtained with a cut-off score of 8.5. The anxiety occurred in 59 patients (58.4%). The OR-PAS is a reliable and valid screening instrument for assessing anxiety in patients at early PD. Anxiety was found in 58.4% of PD patients, demonstrating that anxiety occurs even at early stages. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of encoding condition on free recall in Parkinson's disease: incidental and intentional memory are equally affected.

PubMed

Ellfolk, Ulla; Huurinainen, Salla; Joutsa, Juho; Karrasch, Mira

2012-01-01

Free recall memory deficits are common at early stages of Parkinson's disease (PD). As most studies have used intentional memory tasks, there is little information on how non-intentional, incidental encoding conditions affect memory performance in PD. We studied possible differences between PD patients and controls on free recall using incidental and intentional visual memory tasks. Free recall was examined in relation to attentive/executive functioning and subjective memory complaints. A total of 29 non-demented, medicated PD patients (age 60, disease duration 19 months) and 29 healthy controls (age 61) participated in the study. Incidental free recall was studied using a memory-modification of the Boston naming test (Memo-BNT) and intentional free recall with the 20 Objects test. There was a significant main effect for group due to worse free recall performances in the PD group. No statistically significant interaction between group and encoding condition was observed. The free recall deficit in the PD group was related to cognitive/psychomotor slowing, but not to attentive/executive task demands, or to subjective memory complaints. The results indicate that PD patients are impaired on free recall irrespective of encoding condition.

Exposure to teacher bullying in schools: a study of patients with personality disorders.

PubMed

Monsvold, Toril; Bendixen, Mons; Hagen, Roger; Helvik, Anne-Sofie

2011-10-01

The aim of this study was to examine the level and affect of exposure to teacher bullying in primary and secondary schools on patients with personality disorders (PD). The study group contained 116 people (18-60 years old); 49 patients diagnosed with PD undergoing psychiatric treatment in 10 different psychiatric outpatient clinics in the Southern and Middle part of Norway, and a control group consisting of 67 people who worked in an institution for somatic/elderly people and an institution for people with drug/alcohol dependency in the Middle part of Norway. All study participants filled out a self-report questionnaire, which included demographic data, one item about whether they have been bullied by one or several teachers, and 28 items regarding subjection to negative acts from teachers based on the Negative Acts Questionnaire -Revised (NAQ-R). Patients diagnosed with PD reported significantly more bullying by teachers in both primary school (OR 7.3; 95% CI 1.9-27.7) and secondary school (OR 5.8; 95% CI 1.1-30.5) than healthy controls. Patients with PD also reported a higher prevalence of negative acts from teachers than healthy controls in both primary and secondary schools, such as differential treatment, ridicule, humiliation, and being ignored or neglected at least once weekly. Our findings indicate a correlation between bullying from teachers, as reported by PD patients, and the development of PD in adulthood. The problem of teacher bullying deserves more attention with regard to this possible correlation between student victimization and the development of PD.

Treadmill training improves overground walking economy in Parkinson's disease: a randomized, controlled pilot study.

PubMed

Fernández-Del-Olmo, Miguel Angel; Sanchez, Jose Andres; Bello, Olalla; Lopez-Alonso, Virginia; Márquez, Gonzalo; Morenilla, Luis; Castro, Xabier; Giraldez, Manolo; Santos-García, Diego

2014-01-01

Gait disturbances are one of the principal and most incapacitating symptoms of Parkinson's disease (PD). In addition, walking economy is impaired in PD patients and could contribute to excess fatigue in this population. An important number of studies have shown that treadmill training can improve kinematic parameters in PD patients. However, the effects of treadmill and overground walking on the walking economy remain unknown. The goal of this study was to explore the walking economy changes in response to a treadmill and an overground training program, as well as the differences in the walking economy during treadmill and overground walking. Twenty-two mild PD patients were randomly assigned to a treadmill or overground training group. The training program consisted of 5 weeks (3 sessions/week). We evaluated the energy expenditure of overground walking, before and after each of the training programs. The energy expenditure of treadmill walking (before the program) was also evaluated. The treadmill, but not the overground training program, lead to an improvement in the walking economy (the rate of oxygen consumed per distance during overground walking at a preferred speed) in PD patients. In addition, walking on a treadmill required more energy expenditure compared with overground walking at the same speed. This study provides evidence that in mild PD patients, treadmill training is more beneficial compared with that of walking overground, leading to a greater improvement in the walking economy. This finding is of clinical importance for the therapeutic administration of exercise in PD.

A survey of subjective constipation in Parkinson's disease patients in shanghai and literature review.

PubMed

Gan, Jing; Wan, Ying; Shi, Junjie; Zhou, Mingzhu; Lou, Zhiyin; Liu, Zhenguo

2018-03-15

Constipation is one of the most frequent non-motor symptoms (NMS) in Parkinson's disease (PD) and the prevalence of constipation in PD patients varies among different studies. We designed this study to survey the prevalence and clinical characteristics of subjective constipation and the appearance chronology between the emergence of constipation and onset of motor symptoms in PD patients from Shanghai, China. 268 PD patients were continuously recruited into this study. Parkinson's related clinical information of the participants was collected. A spectrum of motor and nonmotor features was assessed with scales and questionnaires. Subjective constipation was defined by ROME III criteria. 54.10% PD patients suffer from constipation. Among them, there was 47.59% having constipation before onset of motor symptoms. Compared with patients without constipation, patients with constipation reported lower daily water intake and less exercise, and were dominated by bradykinetic-rigid motor phenotype at onset and were prone to have anxiety, depression and insomnia. The time span between constipation and the onset of motor symptoms was (6.62 ± 9.32) years. Constipation occurred more frequently between 2 and 10 years before onset of motor symptoms. Patients suffering with constipation were then divided into two groups according to the time sequence of constipation and motor onset: 'constipation pre-motor sign' group and 'constipation post-motor sign' group. Total timespan from earliest initial symptoms to present was similar. Compared with 'constipation post-motor sign' group, the patients in 'constipation pre-motor sign' group experienced an older motor symptoms onset age, less serious motor symptoms, more serious constipation and less daily levodopa dosage. Our results supported that constipation could be a pre-motor symptom of PD. Different clinical characteristics were found in different constipation-loading time relative to motor symptoms. Research of constipation may be useful to better understand the early stages of PD and assessment of constipation with validated criteria may have utility as a risk factor for predicting PD in the prodromal phase.

Verbal Memory in Parkinson’s Disease: A Combined DTI and fMRI Study

PubMed Central

Lucas-Jiménez, Olaia; Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Ibarretxe-Bilbao, Naroa

2015-01-01

Background: While significant progress has been made to determine the functional role of specific gray matter areas underlying verbal memory in Parkinson’s disease (PD), very little is known about the relationship between these regions and their underlying white matter structures. Objective: The objectives of this study were (1) to investigate verbal memory, fractional anisotropy and brain activation differences between PD patients and healthy controls (HC), (2) to explore the neuroanatomical and neurofunctional correlates of verbal memory in PD, and (3) to investigate the relationship between these neuroanatomical and neurofunctional verbal memory correlates in PD. Methods: Functional magnetic resonance imaging (fMRI) while performing a verbal memory paradigm and diffusion tensor imaging data (DTI), were acquired in 37 PD patients and 15 age-, sex-, and education-matched HC. Results: PD patients showed verbal recognition memory impairment, lower fractional anisotropy in the anterior cingulate tract, and lower brain activation in the inferior orbitofrontal cortex compared to HC. Brain activation in the inferior orbitofrontal cortex correlated significantly with verbal recognition memory impairment in PD patients. In addition, a relationship between brain activation in the inferior orbitofrontal cortex and fractional anisotropy of the uncinate fasciculus was found in PD. Conclusions: These results reveal that deficits in verbal memory in PD are accompanied by functional brain activation changes, but also have specific structural correlates related to white matter microstructural integrity. PMID:27070003

Psychiatric Stigma in Treatment-Seeking Adults with Personality Problems: Evidence from a Sample of 214 Patients

PubMed Central

Catthoor, Kirsten; Schrijvers, Didier; Hutsebaut, Joost; Feenstra, Dineke; Sabbe, Bernard

2015-01-01

Stigmatization is a major burden in adult psychiatric patients with Axis-I diagnoses, as shown consistently in most studies. Significantly fewer studies on the emergence of psychiatric stigma in adult patients with personality disorders (PDs) exist, although the resulting evidence is conclusive. Some authors consider patients with PDs at risk for severe stigmatization because of intense difficulties during interpersonal contact, even in a psychotherapeutic relationship. The aim of this study was primarily the assessment of pre-existing stigma in patients referred for intensive treatment for PDs. The study enrolled 214 patients admitted to the adult department of a highly specialized mental health care institute offering psychotherapy for patients with severe and complex personality pathology. All patients underwent a standard assessment with self-report questionnaires and a semi-structured interview to measure Axis II PDs. The stigma consciousness questionnaire and the perceived devaluation-discrimination questionnaire, both validated instruments, were used to measure perceived and actual experiences of stigma. Independent sample t-tests were used to investigate differences in the mean total stigma scores for patients both with and without a PD. One-way ANOVAs were performed to assess the differences between having a borderline PD, another PD, or no PD diagnosis. Multiple regression main effect analyses were conducted in order to explore the impact of the different PD diagnosis on the level of stigma. The mean scores across all patient groups were consistent with rather low stigma. No differences were found for patients with or without a PD diagnosis. Level of stigma in general was not associated with an accumulating number of PDs. Given the remarkable results, we would strongly recommend further investigations in the field to better understand the phenomenon of stigma in all its aspects. PMID:26217243

Physiotherapists and General Practitioners attitudes towards 'Physio Direct' phone based musculoskeletal Physiotherapy services: a national survey.

PubMed

Harland, Nicholas; Blacklidge, Brian

2017-06-01

Physiotherapy phone based, "Physio Direct" (PD) musculoskeletal triage and treat services are a relatively new phenomena. This study explored Physiotherapist and GP attitudes towards PD services. Online national survey via cascade e-mail initiated by study leads. 488 Physiotherapists and 68 GPs completed the survey. The survey asked three negatively worded and three positively worded Likert scale questions regarding PD services. It also collected demographic data and more global attitudes including a version of the friends and family test. Overall both Physiotherapists and GP's have positive attitudes towards PD services. There was global agreement that PD triage was a good idea but in both groups the majority of respondents who expressed a definite opinion thought that patients would still eventually need to be seen face to face. The vast majority of all respondents also thought patients should be given a choice about first accessing PD services. Physiotherapists with experience of PD services had more positive and less negative attitudes than those without experience. More detailed results are discussed. Relevant clinical stakeholders have generally positive attitudes towards PD services, but more so when they have experience of them. Counter to research findings significant proportions of respondents believe patients accessing PD services will still need to be seen face to face. The significant majority of respondents believe patients should be given a choice whether they access PD services in the first instance or not. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

PubMed

Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

2017-01-01

Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease.

PubMed

Oeda, Tomoko; Umemura, Atsushi; Mori, Yuko; Tomita, Satoshi; Kohsaka, Masayuki; Park, Kwiyoung; Inoue, Kimiko; Fujimura, Harutoshi; Hasegawa, Hiroshi; Sugiyama, Hiroshi; Sawada, Hideyuki

2015-12-01

Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival time analysis followed a maximum 12-year observation (median 6.0 years), revealing that PD patients with GD-associated mutations developed dementia and psychosis significantly earlier than those without mutations (p < 0.001 and p = 0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically significant differences were observed for wearing-off and dyskinesia between the groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in the bilateral parietal cortex, including the precuneus of GD-associated mutant PD patients, compared with matched PD controls without mutations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The effects of dual tasking on handwriting in patients with Parkinson's disease.

PubMed

Broeder, S; Nackaerts, E; Nieuwboer, A; Smits-Engelsman, B C M; Swinnen, S P; Heremans, E

2014-03-28

Previous studies have shown that patients with Parkinson's disease (PD) experience extensive problems during dual tasking. Up to now, dual-task interference in PD has mainly been investigated in the context of gait research. However, the simultaneous performance of two different tasks is also a prerequisite to efficiently perform many other tasks in daily life, including upper limb tasks. To address this issue, this study investigated the effect of a secondary cognitive task on the performance of handwriting in patients with PD. Eighteen PD patients and 11 age-matched controls performed a writing task involving the production of repetitive loops under single- and dual-task conditions. The secondary task consisted of counting high and low tones during writing. The writing tests were performed with two amplitudes (0.6 and 1.0cm) using a writing tablet. Results showed that dual-task performance was affected in PD patients versus controls. Dual tasking reduced writing amplitude in PD patients, but not in healthy controls (p=0.046). Patients' writing size was mainly reduced during the small-amplitude condition (small amplitude p=0.017; large amplitude p=0.310). This suggests that the control of writing at small amplitudes requires more compensational brain-processing recourses in PD and is as such less automatic than writing at large amplitudes. In addition, there was a larger dual-task effect on the secondary task in PD patients than controls (p=0.025). The writing tests on the writing tablet proved highly correlated to daily life writing as measured by the 'Systematic Screening of Handwriting Difficulties' test (SOS-test) and other manual dexterity tasks, particularly during dual-task conditions. Taken together, these results provide additional insights into the motor control of handwriting and the effects of dual tasking during upper limb movements in patients with PD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Spontaneous Swallowing during All-Night Sleep in Patients with Parkinson Disease in Comparison with Healthy Control Subjects

PubMed Central

Uludag, Irem Fatma; Tiftikcioglu, Bedile Irem; Ertekin, Cumhur

2016-01-01

Study Objectives: Spontaneous saliva swallows (SS) appear especially during sleep. The rate of SS was rarely investigated in all-night sleep in patients with Parkinson disease (PD). Dysphagia is a frequent symptom in PD, but the rate of SS was never studied with an all-night sleep electroencephalogram (EEG). Methods: A total of 21 patients with PD and 18 age-matched healthy controls were included in the study. Frequencies of SS and coughing were studied in all-night sleep recordings of patients with PD and controls. During all-night sleep, video-EEG 12-channel recording was used including the electromyography (EMG) of the swallowing muscles, nasal airflow, and recording of vertical laryngeal movement using a pair of EEG electrodes over the thyroid cartilage. Results: The total number of SS was increased while the mean duration of sleep was decreased in PD when compared to controls. Sialorrhea and clinical dysphagia, assessed by proper questionnaires, had no effect in any patient group. The new finding was the so-called salvo type of consecutive SS in one set of swallowing. The amount of coughing was significantly increased just after the salvo SS. Conclusions: In PD, the rate of SS was not sufficient to demonstrate the swallowing disorder, such as oropharyngeal dysphagia, but the salvo type of SS was quite frequent. This is a novel finding and may contribute to the understanding of swallowing problems in patients with dysphagic or nondysphagic PD. Citation: Uludag IF, Tiftikcioglu BI, Ertekin C. Spontaneous swallowing during all-night sleep in patients with Parkinson disease in comparison with healthy control subjects. SLEEP 2016;39(4):847–854. PMID:26943467

Assessment of physical activity, capacity and nutritional status in elderly peritoneal dialysis patients.

PubMed

Cupisti, Adamasco; D'Alessandro, Claudia; Finato, Viviana; Del Corso, Claudia; Catania, Battista; Caselli, Gian Marco; Egidi, Maria Francesca

2017-05-30

This study aimed to evaluate the prevalence of sedentarism, and to assess physical capacity and nutritional status in a cohort of older patients on peritoneal dialysis (PD), with respect to age-matched non-dialysis CKD population, using highly accessible, simple methods, namely the Rapid Assessment of Physical activity (RAPA) test and the 30″ Sit-to-stand (STS) test. This cross-sectional multicenter study included 151 renal patients older than 60 years; 71 pts. (44 m, age 72 ± 7 yrs) were on PD and 80 pts. (63 m, age 74 ± 7 yrs) were affected by 3-4 stage CKD. The prevalence of sedentary/underactive patients was double of that of the active patients as assessed by RAPA test, both in the PD (65.3%) and in the CKD (67.5%) cohort. The 30"STS test showed a reduced physical performance in both groups: 84.5% of PD patients and 87.5% of CKD patients did not reach the expected number of stands by age and gender. A malnutrition-inflammation score (MIS) ≥ 6 occurred in 37 % of PD patients and in 2.5 % of CKD patients. In PD patients, an independent significant association was observed between 30"STS test and MIS (beta -0.510, p = 0.013), as well as between RAPA and MIS (beta -0.544, p = 003) and phase angle (beta -0.506, p = 0.028). A high prevalence of low- performance capacity and sedentarism has been detected among elderly patients on PD or with CKD stage 3-4. Apart from age, a condition of malnutrition-inflammation was the major determinant of poor physical activity and capacity in PD patients. Better body composition seems to be positively associated with physical activity in PD and with physical capacity in CKD patients. Routine clinical management should include a close evaluation of nutritional status and evaluation of physical activity and capacity which can be easily assessed by RAPA and 30″STS tests.

[PD1/PD-L1 immunohistochemistry in thoracic oncology: Where are we?

PubMed

Hofman, Paul; Ilié, Marius; Lassalle, Sandra; Long, Elodie; Bence, Coraline; Butori, Catherine; Hofman, Véronique

2017-02-01

The assays for the assessment of the PD-L1 status by immunohistochemistry are available in clinical studies in thoracic oncology to predict response to immunotherapies targeting the PD-1/PD-L1 pathway. With the arrival of this new class of molecules in second line and very soon in first line of treatment for patients with advanced or metastatic non-small cell lung cancer, these tests will certainly be required in routine once these new drugs will be granted marketing authorization. The rapid introduction of these "companion" or "complementary" tests seems essential to select patients to benefit from these effective but also expensive and sometimes toxic therapies. Although challenged by some oncologists (as some patients not expressing PD-L1 may sometimes respond to PD-1/PD-L1 blockade), the anti-PD-L1 immunohistochemically approach seems inevitable in 2017. This new activity developed in the pathology laboratories raises several questions: which anti-PD-L1 clone should be used? On which device? What threshold of positivity should be considered? Should PD-L1 expression be assessed on tumor cells as well as on the immune cells? What controls should be used? Comparative studies are underway or have been already implemented in order to answer some of these questions. This review addresses the different evaluation criteria for immunohistochemistry using the main anti-PD-L1 antibodies used to date as well the recently published studies using these antibodies in thoracic oncology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

PD-1/PD-L1 pathway inhibitors in advanced prostate cancer.

PubMed

Isaacsson Velho, Pedro; Antonarakis, Emmanuel S

2018-05-01

Pharmacological inhibition of immune checkpoint receptors or their ligands represents a transformative breakthrough in the management of multiple cancers. However, immune checkpoint inhibitors have yet to be FDA-approved for the management of metastatic prostate cancer (PCa), the commonest non-cutaneous malignancy in men. Areas covered: We review our current understanding of the PD-1/PD-L1 pathway in cancer, the use of anti-PD-1/PD-L1 therapeutics in PCa, and potential subgroups of PCa patients who may derive the greatest benefit from these agents (such as men with tumors that have expression of PD-L1 and/or high mutational load). We also review the prior and current clinical trials evaluating the blockade of PD-1/PD-L1 in PCa, highlighting some of the key ongoing studies of greatest relevance to the field. Expert commentary: Clinical trials investigating PD-1/PD-L1 inhibitors should be encouraged in patients with PCa. While it is unlikely that immune checkpoint monotherapies will produce long-lasting responses in a substantial proportion of patients, there is early evidence of activity in some patient subsets. These subgroups may include those with high PD-L1 expression, those with hypermutated or microsatellite-unstable tumors, and those enriched for germline and/or somatic DNA-repair gene mutations (e.g. intraductal/ductal histology, primary Gleason pattern 5, and perhaps AR-V7-positive tumors).

Lifetime costs for peritoneal dialysis and hemodialysis in patients in Taiwan.

PubMed

Kao, Tze-Wah; Chang, Yu-Yin; Chen, Pau-Chung; Hsu, Chih-Cheng; Chang, Yu-Kang; Chang, Yu-Hung; Lee, Lukas Jyuhn-Hsiarn; Wu, Kwan-Dun; Tsai, Tun-Jun; Wang, Jung-Der

2013-01-01

This study compared the lifetime costs for peritoneal dialysis (PD) and hemodialysis (HD) patients in Taiwan. Using the National Health Insurance (NHI) database of all end-stage renal disease patients on maintenance dialysis registered from July 1997 to December 2005, we matched eligible PD patients with eligible HD patients on age, sex, and diabetes status. The matched patients were followed until 31 December 2006. Patients were excluded if they were less than 18 years of age, had been diagnosed with cancer before dialysis, or had been dialyzed at centers or clinics other than hospitals. Outcomes-including life expectancy, total lifetime costs, and costs per life-year paid by the NHI-were estimated and compared. The 3136 pairs of matched PD and HD patients had a mean age of 53.2 ± 15.4 years. The total lifetime cost for PD patients (US$139 360 ± US$8 336) was significantly lower than that for HD patients (US$185 235 ± US$9 623, p < 0.001). Except for patients with diabetes (who had a short life expectancy), the total lifetime cost was significantly lower for PD patients than for HD patients regardless of sex and age (p < 0.01). In Taiwan, the total lifetime costs paid by the NHI were lower for PD than for HD patients.

Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation.

PubMed

Pham, Uyen Ha Gia; Andersson, Stein; Toft, Mathias; Pripp, Are Hugo; Konglund, Ane Eidahl; Dietrichs, Espen; Malt, Ulrik Fredrik; Skogseid, Inger Marie; Haraldsen, Ira Ronit Hebolt; Solbakk, Anne-Kristin

2015-01-01

Objective. Studies on the effect of subthalamic deep brain stimulation (STN-DBS) on executive functioning in Parkinson's disease (PD) are still controversial. In this study we compared self-reported daily executive functioning in PD patients before and after three months of STN-DBS. We also examined whether executive functioning in everyday life was associated with motor symptoms, apathy, and psychiatric symptoms. Method. 40 PD patients were examined with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), the Symptom Checklist 90-Revised (SCL-90-R), and the Apathy Evaluation Scale (AES-S). Results. PD patients reported significant improvement in daily life executive functioning after 3 months of STN-DBS. Anxiety scores significantly declined, while other psychiatric symptoms remained unchanged. The improvement of self-reported executive functioning did not correlate with motor improvement after STN-DBS. Apathy scores remained unchanged after surgery. Only preoperative depressed mood had predictive value to the improvement of executive function and appears to prevent potentially favorable outcomes from STN-DBS on some aspects of executive function. Conclusion. PD patients being screened for STN-DBS surgery should be evaluated with regard to self-reported executive functioning. Depressive symptoms in presurgical PD patients should be treated. Complementary information about daily life executive functioning in PD patients might enhance further treatment planning of STN-DBS.

Effect of hemodialysis and peritoneal dialysis on redox status in chronic renal failure patients: a comparative study.

PubMed

Mekki, Khedidja; Taleb, Warda; Bouzidi, Nassima; Kaddous, Abbou; Bouchenak, Malika

2010-09-03

To investigate the effects of hemodialysis (HD) and periotoneal dialysis (PD) on oxidative stress in chronic renal failure patients (CRF). 20 HD patients (M/F: 8/12, 36 ± 12 years) and 20 PD patients (M/F: 10/10, 40 ± 8 years) were compared with 20 end stage renal failure patients (CRF) (M/F: 4/16, 61 ± 13 years). Thiobarbituric acid reactive substances (TBARS) values were elevated in HD and decreased in PD compared to CRF (P < 0.05). TBARS-VLDL and TBARS-HDL2 were decreased in HD and PD, compared to CRF (p < 0.05). TBARS-LDL were higher in HD compared to CRF (p < 0.05). No significant difference in TBARS-HDL3 values between the three groups. Carbonyls were increased in HD (p < 0.05) and PD (p < 0.01) compared to CRF. Plasma superoxide dismutase activity (SOD) was decreased in HD compared to CRF and PD (P < 0.05). Glutathion peroxidase activity (GSH-Px) was decreased in HD and PD (P < 0.005), compared to CRF. Decrease in catalase activity was noted only in PD compared to CRF (P < 0.05). An increase in nitric oxide was noted in HD compared to CRF (p < 0.05). Albumin concentrations were higher in HD and PD compared to CRF (P < 0.001). Whereas uric acid concentrations were decreased in HD (P < 0.001) compared to CRF and PD. Bilirubin values were similar in all groups. Increased values of iron were noted in HD and PD, compared to PD (p < 0.001). HD and PD aggravate oxidative stress generated by uremia. HD accentuates lipid and protein peroxidation, while PD aggravates protein oxidation. However, the activity of antioxidant enzymes was altered by both dialysis treatments.

Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.

PubMed

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 ( PDCD1 ) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation ( mPD-1 ) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = -0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35-4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16-3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies.

Evaluation of serum and gingival crevicular fluid C-reactive protein and IL-6 levels in patients with periodontitis and transient ischemic attacks.

PubMed

Haba, Danisia; Teslaru, Silvia; Ungureanu, Didona; Hodorog, Diana; Alecu, C; Benghiac, Ana Gabriela; Zetu, L; Ancuţa, Codrina; Ancuţa, E; Nemţoi, A; Iordache, Cristina

2011-01-01

Recent advances have suggested that periodontitis (PD), the paradigm of chronic infection in dental pathology, shares several pathogenic pathways with cardio- and cerebro-vascular disorders (CVD), based on inflammatory mediators including IL-1, IL-6, TNF-α. To assess pro-inflammatory biomarkers (C-reactive protein - CRP, IL-6) in serum and gingival crevicular fluid (GCF) in patients with PD and with transient ischemic attacks (TIAs). Prospective observational study on 143 patients classified as follows: 40 healthy subjects (group A), 50 PD patients (group B) and 53 PD-TIAs patients (group C). The predefined assessment protocol has included: current medical data, risk factors for CRP changes, periodontal status (clinical, orthopantomography, Schei Ruler technique), inflammatory biomarkers (CRP, IL-6). High serum CRP and IL-6 have been reported in both TIAs and PD, while statistically significant increase in GCF CRP only in PD-TIAs (p<0.05). Moreover, both generalized and localized chronic PD may be at higher risk for CVD, since CRP level was higher in these subgroups. However, no significant differences were reported in serum IL-6 between generalized and localized PD. A score function was demonstrated, including bone loss degree, bleeding index, collection site depth, serum and GCF IL-6 and CRP, tooth loss, allowing the classification of PD based on risk for developing TIAs. CRP and IL-6 are commonly involved in the pathways of PD and TIAs. Interdisciplinary assessment should be promoted in order to implement the stratification of PD patients according to the risk for TIAs as suggested by the proposed algorithm.

[Reason for "choosing" peritoneal dialysis: exhaustion of vascular access for hemodialysis?].

PubMed

Rocha, Paulo Novis; Sallenave, Mila; Casqueiro, Verena; Campelo Neto, Bolivar; Presídio, Sérgio

2010-03-01

Little is known about the prognosis of patients beginning peritoneal dialysis (PD) as their last alternative. To describe the clinical-demographic profile of patients switching from hemodialysis (HD) to PD, due to exhaustion of the HD vascular access, and the occurrence of peritonitis among them. Review of the medical records of all patients in the PD program of the Hospital Roberto Santos in the city of Salvador, state of Bahia, Brazil. The study comprised 22 patients (median age, 47.9 years), 54.5% of whom were men, 84.2%, black or mulattoes, and 68.2% originated from the inner Bahia state. Peritoneal dialysis was the initial modality of renal substitutive therapy (RST) in only four of those patients. The remaining 18 patients began RST through HD, mainly on an emergency basis and by using double-lumen catheter (DLC). In a median of 7.7 months on HD, most patients (64.7%) used four or more DLCs. In only 7/18 (39%) patients, the switch from HD to PD was based on the patient';s choice; in most cases, 11/18 (61%), the reason for switching to PD was exhaustion of HD vascular access. Peritonitis was more frequent in patients switching to PD due to exhaustion of HD vascular access than in the rest of the group. Initiating RST on an emergency basis through HD and using DLC may lead to a fast exhaustion of vascular access, leaving PD as the only viable option. This inadequate mode of patient "selection" for PD is associated with a higher risk for peritonitis.

Circulating programmed death ligand-1 (cPD-L1) in non-small-cell lung cancer (NSCLC)

PubMed Central

Vecchiarelli, Silvia; Passiglia, Francesco; D’Incecco, Armida; Gallo, Marianna; De Luca, Antonella; Rossi, Elisa; D’Incà, Federica; Minuti, Gabriele; Landi, Lorenza; Bennati, Chiara; Spreafico, Michela; D’Arcangelo, Manolo; Mazza, Valentina; Normanno, Nicola; Cappuzzo, Federico

2018-01-01

Background This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients’ clinical responses and survival outcome. Methods Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher’s test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and p-value. Results Baseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort (p = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; p = 0.002), with no changes in patients exposed to non-chemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; p = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months (p = 0.062) and 8.8 vs 9.3 months (p = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant (p = 0.063). Conclusions This study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations. PMID:29707129

Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1–targeted therapy in lung cancer patients

PubMed Central

Kamphorst, Alice O.; Pillai, Rathi N.; Yang, Shu; Nasti, Tahseen H.; Sica, Gabriel L.; Yu, Ke; Koenig, Lydia; Patel, Nikita T.; Behera, Madhusmita; Wu, Hong; McCausland, Megan; Chen, Zhengjia; Zhang, Chao; Khuri, Fadlo R.; Owonikoko, Taofeek K.; Ahmed, Rafi; Ramalingam, Suresh S.

2017-01-01

Exhausted T cells in chronic infections and cancer have sustained expression of the inhibitory receptor programmed cell death 1 (PD-1). Therapies that block the PD-1 pathway have shown promising clinical results in a significant number of advanced-stage cancer patients. Nonetheless, a better understanding of the immunological responses induced by PD-1 blockade in cancer patients is lacking. Identification of predictive biomarkers is a priority in the field, but whether peripheral blood analysis can provide biomarkers to monitor or predict patients’ responses to treatment remains to be resolved. In this study, we analyzed longitudinal blood samples from advanced stage non–small cell lung cancer (NSCLC) patients (n = 29) receiving PD-1–targeted therapies. We detected an increase in Ki-67+ PD-1+ CD8 T cells following therapy in ∼70% of patients, and most responses were induced after the first or second treatment cycle. This T-cell activation was not indiscriminate because we observed only minimal effects on EBV-specific CD8 T cells, suggesting that responding cells may be tumor specific. These proliferating CD8 T cells had an effector-like phenotype (HLA-DR+, CD38+, Bcl-2lo), expressed costimulatory molecules (CD28, CD27, ICOS), and had high levels of PD-1 and coexpression of CTLA-4. We found that 70% of patients with disease progression had either a delayed or absent PD-1+ CD8 T-cell response, whereas 80% of patients with clinical benefit exhibited PD-1+ CD8 T-cell responses within 4 wk of treatment initiation. Our results suggest that peripheral blood analysis may provide valuable insights into NSCLC patients’ responses to PD-1–targeted therapies. PMID:28446615

Artistic productivity and creative thinking in Parkinson's disease.

PubMed

Canesi, M; Rusconi, M L; Isaias, I U; Pezzoli, G

2012-03-01

Creative drive and enhanced artistic-like production may emerge in patients with Parkinson's disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic-like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs). We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD-c) or without (PD-nc) increased artistic-like production and 36 healthy controls (HC). We considered artistic-like productivity to be enhanced if patients reported working on any form of art more than 2h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied. Mean TTCT score of PD-c was found to be similar to HC (169.4±51.6 vs. 170.2±69.7, respectively), and both PD-c and HC had significantly higher TTCT scores than patients with PD-nc (125.4±46.1 P<0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS-11A, and MIDI. Our study suggests that newly acquired artistic-like production in patients with PD is not associated with impulsivity or ICDs. Artistic-like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson’s patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study

PubMed Central

Ray, Nicola J.; Miyasaki, Janis M.; Zurowski, Mateusz; Ko, Ji Hyun; Cho, Sang Soo; Pellecchia, Giovanna; Antonelli, Francesca; Houle, Sylvain; Lang, Anthony E.; Strafella, Antonio P.

2012-01-01

Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson’s disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait. PMID:22766031

Dreaming furiously? A sleep laboratory study on the dream content of people with Parkinson's disease and with or without rapid eye movement sleep behavior disorder.

PubMed

Valli, Katja; Frauscher, Birgit; Peltomaa, Taina; Gschliesser, Viola; Revonsuo, Antti; Högl, Birgit

2015-03-01

Rapid eye movement (REM) sleep behavior disorder (RBD) has been related to altered, action-filled, vivid, and aggressive dream content, but research comparing the possible differences in dreams of Parkinson's disease (PD) patients with and without RBD is scarce. The dream content of PD patients with and without RBD was analyzed with specific focus on action-filledness, vividness, emotional valence, and threats. A total of 69 REM and NREM dream reports were collected in the sleep laboratory, 37 from nine PD patients with RBD and 32 from six PD patients without RBD. A content analysis of (1) action-filledness (actions and environmental events); (2) vividness (emotions and cognitive activity); (3) intensity of actions, events and emotions; (4) emotional valence, and (5) threatening events was performed on the transcripts. Altogether 563 dream elements expressing action-filledness and vividness were found. There were no significant between-group differences in the number or distribution of elements reflecting action-filledness or vividness, emotional valence or threats. In within-group analyses, PD patients with RBD had significantly more negative compared to positive dreams (p = 0.012) and compared to PD patients without RBD, a tendency to have more intense actions in their dreams (p = 0.066). Based on the results of this study, there are no major between-group differences in the action-filledness, vividness, or threat content of dreams of PD patients with and without RBD. However, within-group analyses revealed that dreams were more often negatively than positively toned in PD patients with RBD. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of surgical outcomes between open and robot-assisted minimally invasive pancreaticoduodenectomy.

PubMed

Kim, Hyeong Seok; Han, Youngmin; Kang, Jae Seung; Kim, Hongbeom; Kim, Jae Ri; Koon, Wooil; Kim, Sun-Whe; Jang, Jin-Young

2018-02-01

Robot surgery is a new method that maintains advantages and overcomes disadvantages of conventional methods, even in pancreatic surgery. This study aimed to evaluate safety and benefits of robot-assisted minimally invasive pancreaticoduodenectomy (robot PD). This study included 237 patients who underwent PD between 2015 and 2017. Demographics and surgical outcomes were evaluated. Fifty-one patients underwent robot PD and 186 underwent open PD. Robot PD group had younger age (60.7 vs. 65.4 years, P = 0.006) and lower body mass index (22.7 vs. 24.0, P = 0.007). Robot PD group had lower proportion of patients with firm or hard pancreatic texture (15.7% vs. 38.2%, P = 0.004) and smaller pancreatic duct size (2.3 vs. 3.3 mm, P = 0.002). Two groups had similar operation time (robot vs. open: 335.6 vs. 330.1 min) and complications (15.7% vs. 21.0%), including postoperative pancreatic fistula rate (6.0% vs. 12.0%). Robot PD group had lower postoperative pain score (3.7 vs. 4.1 points, P = 0.008), and shorter postoperative stay (10.6 vs. 15.3 days, P = 0.001). Robot PD is comparable to open PD in early outcomes. Robot PD is safe and feasible and enables early recovery; indication for robot PD is expected to expand in the near future. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Daytime REM Sleep in Parkinson’s Disease

PubMed Central

Bliwise, Donald L.; Trotti, Lynn Marie; Juncos, Jorge J.; Factor, Stewart A.; Freeman, Alan; Rye, David B.

2012-01-01

Background Previous studies have demonstrated both clinical and neurochemical similarities between Parkinson’s disease (PD) and narcolepsy. The intrusion of REM sleep into the daytime remains a cardinal feature of narcolepsy, but the importance of these intrusions in PD remains unclear. In this study we examined REM sleep during daytime Maintenance of Wakefulness Testing (MWT) in PD patients. Methods Patients spent 2 consecutive nights and days in the sleep laboratory. During the daytime, we employed a modified MWT procedure in which each daytime nap opportunity (4 per day) was extended to 40 minutes, regardless of whether the patient was able to sleep or how much the patient slept. We examined each nap opportunity for the presence of REM sleep and time to fall asleep. Results Eleven of 63 PD patients studied showed 2 or more REM episodes and 10 showed 1 REM episode on their daytime MWTs. Nocturnal sleep characteristics and sleep disorders were unrelated to the presence of daytime REM sleep, however, patients with daytime REM were significantly sleepier during the daytime than those patients without REM. Demographic and clinical variables, including Unified Parkinson’s Disease Rating Scale motor scores and levodopa dose equivalents, were unrelated to the presence of REM sleep. Conclusions A sizeable proportion of PD patients demonstrated REM sleep and daytime sleep tendency during daytime nap testing. These data confirm similarities in REM intrusions between narcolepsy and PD, perhaps suggesting parallel neurodegenerative conditions of hypocretin deficiency. PMID:22939103

Multidisciplinary Approach to Esophageal Achalasia: A Single Center Experience.

PubMed

Schlottmann, Francisco; Andolfi, Ciro; Kavitt, Robert T; Konda, Vani J A; Patti, Marco G

2017-04-01

The treatment of achalasia is palliative. Pneumatic dilatation (PD) or laparoscopic Heller myotomy (LHM) just eliminates the outflow obstruction allowing easier emptying of the esophagus. The aim of this study was to evaluate the results of a multidisciplinary approach to esophageal achalasia. A consecutive series of patients with achalasia treated by a multidisciplinary esophageal team consisting of radiologists, gastroenterologists, and surgeons in a quaternary care center between May 2008 and April 2015 were analyzed. A total of 147 patients with achalasia underwent LHM and partial fundoplication. Sixty-two patients (42%) had been treated preoperatively with PD and/or botulinum toxin (BT). The preoperative Eckardt score (ES) was 6.4 ± 2. At a median follow-up of 22 months, 128 patients (87%) did well and required no further treatment (ES 0.1). The remaining 19 patients (13%) had recurrence of symptoms and required further treatment: 12 were treated with PD and improved (ES 0.7); 4 were treated with PD and BT and improved (ES 1.3); 3 failed PD. These 3 patients had been treated with multiple sessions of PD and BT before the myotomy. Overall, 144 patients (98%) did well with laparoscopic (87%) or laparoscopic and endoscopic treatment (11%). The results of this study show that (a) LHM is an effective treatment modality, (b) PD improved symptoms in the majority of patients with recurrent dysphagia after myotomy and (c) multiple preoperative endoscopic treatments seem to affect outcomes of LHM. Patients with achalasia should be treated in a quaternary care center by a multidisciplinary team.

TEMPORAL TRENDS AND FACTORS ASSOCIATED WITH MEDICATION PRESCRIPTION PATTERNS IN PERITONEAL DIALYSIS PATIENTS.

PubMed

Campos, Ludimila G; Bragg-Gresham, Jennifer; Han, Yun; Moraes, Thyago P; Figueiredo, Ana E; Barretti, Pasqual; Balkrishnan, Rajesh; Saran, Rajiv; Pecoits-Filho, Roberto

2018-06-06

Patients on peritoneal dialysis (PD) suffer from a high burden of comorbidities, which are managed with multiple medications. Determinants of prescription patterns are largely unknown in this population. This study assesses temporal changes and factors associated with medication prescription in a nationally representative population of patients on PD under the universal coverage healthcare system in Brazil. Incident patients recruited in the Brazilian Peritoneal Dialysis Study (BRAZPD) from December 2004 to January 2011, stratified by prior hemodialysis (HD) treatment, were included in the analysis. Multivariable logistic regression was used to assess the association between medication prescription and socioeconomic factors. Yearly prevalent cross-sections were calculated to estimate prescription over time. Medication prescription was in general higher among patients who had previously received HD, compared with those who started renal replacement therapy (RRT) directly on PD. Prescription increased from baseline to 6 months of PD therapy, particularly in those who did not previously receive HD. After accounting for patient characteristics, significant associations were found between socioeconomic factors, geographic region, and medication prescription patterns. Finally, the prescription of all cardioprotective and anemia medications and phosphate binders increased significantly over time. In a PD population under universal coverage in a developing country, there was an increase in drug prescription during the first 6 months on PD, and a trend toward more liberal prescription of medications in later years. Independent from patient characteristics and comorbidities, socioeconomic factors influenced drug prescriptions that likely impact patient outcome, calling for public health action to decrease potential inequities in management of comorbidities in PD patients.

Depression in Parkinson's disease: convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus.

PubMed

Cardoso, Ellison Fernando; Maia, Fernanda Martins; Fregni, Felipe; Myczkowski, Martin Luis; Melo, Luciano M; Sato, João R; Marcolin, Marco Antonio; Rigonatti, Sergio P; Cruz, Antonio Cesário; Barbosa, Egberto Reis; Amaro, Edson

2009-08-15

Depression is the most frequent psychiatric disorder in Parkinson's disease (PD). Although evidence suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontal cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation.

Correlation of Visuospatial Ability and EEG Slowing in Patients with Parkinson's Disease

PubMed Central

Meyer, Antonia; Chaturvedi, Menorca; Hatz, Florian; Gschwandtner, Ute

2017-01-01

Background. Visuospatial dysfunction is among the first cognitive symptoms in Parkinson's disease (PD) and is often predictive for PD-dementia. Furthermore, cognitive status in PD-patients correlates with quantitative EEG. This cross-sectional study aimed to investigate the correlation between EEG slowing and visuospatial ability in nondemented PD-patients. Methods. Fifty-seven nondemented PD-patients (17 females/40 males) were evaluated with a comprehensive neuropsychological test battery and a high-resolution 256-channel EEG was recorded. A median split was performed for each cognitive test dividing the patients sample into either a normal or lower performance group. The electrodes were split into five areas: frontal, central, temporal, parietal, and occipital. A linear mixed effects model (LME) was used for correlational analyses and to control for confounding factors. Results. Subsequently, for the lower performance, LME analysis showed a significant positive correlation between ROCF score and parietal alpha/theta ratio (b = .59, p = .012) and occipital alpha/theta ratio (b = 0.50, p = .030). No correlations were found in the group of patients with normal visuospatial abilities. Conclusion. We conclude that a reduction of the parietal alpha/theta ratio is related to visuospatial impairments in PD-patients. These findings indicate that visuospatial impairment in PD-patients could be influenced by parietal dysfunction. PMID:28348918

Programmed cell death-1 and programmed cell death ligand-1 antibodies-induced dysthyroidism.

PubMed

Jaafar, Jaafar; Fernandez, Eugenio; Alwan, Heba; Philippe, Jacques

2018-05-01

Monoclonal antibodies blocking the programmed cell death-1 (PD-1) or its ligand (PD-L1) are a group of immune checkpoints inhibitors (ICIs) with proven antitumor efficacy. However, their use is complicated by immune-related adverse events (irAEs), including endocrine adverse events (eAEs). We review the incidence, time to onset and resolution rate of dysthyroidism induced by PD-1/PD-L1 Ab, and the clinical, biological and radiological findings. We aim to discuss the potential mechanisms of PD-1/PD-L1 Ab-induced dysthyroidism, and to propose a management algorithm. We performed a literature search of available clinical trials regarding PD-1/PD-L1 Ab in the PubMed database. We selected all English language clinical trials that included at least 100 patients. We also present selected case series or reports, retrospective studies and reviews related to this issue. In patients treated with PD-1 Ab, hypothyroidism occurred in 2-10.1% and hyperthyroidism occurred in 0.9-7.8%. When thyroiditis was reported separately, it occurred in 0.34-2.6%. Higher rates were reported when PD-1 Ab were associated with other ICI or chemotherapy. The median time to onset of hyperthyroidism and hypothyroidism after PD-1 Ab initiation was 23-45 days and 2-3.5 months, respectively. Regarding PD-L1 Ab, hypothyroidism occurred in 0-10% and hyperthyroidism in 0.5-2% of treated patients. The average time to onset of dysthyroidism after PD-L1 Ab was variable and ranged from 1 day after treatment initiation to 31 months. Dysthyroidism occurs in up to 10% of patients treated with PD-1/PD-L1 Ab. Hypothyroidism and reversible destructive thyroiditis are the most frequent endocrine adverse events (eAE) in PD-1/PD-L1 treated patients. Immune and non-immune mechanisms are potentially involved, independently of the presence of thyroid antibodies. © 2018 The authors.

Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study.

PubMed

Yamauchi, Ichiro; Sakane, Yoriko; Fukuda, Yorihide; Fujii, Toshihito; Taura, Daisuke; Hirata, Masakazu; Hirota, Keisho; Ueda, Yohei; Kanai, Yugo; Yamashita, Yui; Kondo, Eri; Sone, Masakatsu; Yasoda, Akihiro; Inagaki, Nobuya

2017-07-01

The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international Phase 3 studies and national post-marketing surveillance of nivolumab in Japan. This study analyzed five consecutive cases with thyroid dysfunction associated with nivolumab therapy. Second, it examined the mRNA and protein expressions of PD-L1 and PD-L2 by reverse transcription polymerase chain reaction and Western blotting. All patients were diagnosed with painless thyroiditis. Thyrotoxicosis developed within four weeks from the first administration of nivolumab and normalized within four weeks of onset in three of the five patients. Hypothyroidism after transient thyrotoxicosis developed in two patients, and preexisting hypothyroidism persisted in one patient. The other two patients were treated with glucocorticoids and discontinued nivolumab therapy for comorbid adverse events. One did not develop hypothyroidism, and the other developed mild, transient hypothyroidism. In addition, it was verified that normal thyroid tissue expresses PD-L1 and PD-L2 mRNA and those proteins. In the present cases, nivolumab-induced thyrotoxicosis seemed to be associated with painless thyroiditis, while no patient with Graves' disease was observed. A transient and rapid course with subsequent hypothyroidism was observed in nivolumab-induced thyroiditis. In addition, it was verified that PD-L1 and PD-L2 are expressed in normal thyroid tissue. This suggests that nivolumab therapy reduces immune tolerance, even in normal thyroid tissue, and leads to the development of thyroiditis. Treating thyrotoxicosis with only supportive care and considering levothyroxine replacement therapy once subsequent hypothyroidism occurs is proposed. Further investigations are required to confirm whether glucocorticoid therapy and discontinuation of nivolumab therapy prevent subsequent hypothyroidism.

Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The balANZ Trial

PubMed Central

Cho, Yeoungjee; Johnson, David W.; Vesey, David A.; Hawley, Carmel M.; Clarke, Margaret; Topley, Nicholas

2015-01-01

♦ Background: The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. ♦ Methods: The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. ♦ Results: Baseline albuminuria was not a useful predictor of change in RRF in PD patients (p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population (p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model (p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon γ-induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. ♦ Conclusions: Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving biocompatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary biomarkers as tools to predict RRF decline in PD patients. PMID:24711637

Alteration of the fecal microbiota in Chinese patients with Parkinson's disease.

PubMed

Qian, Yiwei; Yang, Xiaodong; Xu, Shaoqing; Wu, Chunyan; Song, Yanyan; Qin, Nan; Chen, Sheng-Di; Xiao, Qin

2018-05-01

Emerging evidences suggest that gut microbiota dysbiosis plays a role in Parkinson's disease (PD). However, the alterations in fecal microbiome in Chinese PD patients remains unknown. This case-control study was conducted to explore fecal microbiota compositions in Chinese PD patients. Microbiota communities in the feces of 45 patients and their healthy spouses were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene. The relationships between fecal microbiota and PD clinical characteristics were analyzed. The structure and richness of the fecal microbiota differed between PD patients and healthy controls. Genera Clostridium IV, Aquabacterium, Holdemania, Sphingomonas, Clostridium XVIII, Butyricicoccus and Anaerotruncus were enriched in the feces of PD patients after adjusting for age, gender, body mass index (BMI), and constipation. Furthermore, genera Escherichia/Shigella were negatively associated with disease duration. Genera Dorea and Phascolarctobacterium were negatively associated with levodopa equivalent doses (LED). Among the non-motor symptoms (NMSs), genera Butyricicoccus and Clostridium XlVb were associated with cognitive impairment. Overall, we confirmed that gut microbiota dysbiosis occurs in Chinese patients with PD. A well-controlled population involved was beneficial for the identification of microbiota associated with diseases. Additionally, the fecal microbiota was closely related to PD clinical characteristics. Elucidating these differences in the fecal microbiome will provide a foundation to improve our understanding the pathogenesis of PD and to support the potentially therapeutic options modifying the gut microbiota. Copyright © 2018 Elsevier Inc. All rights reserved.

Knowledge of Parkinson's Disease in a Multiethnic Urban Asian Setting.

PubMed

Tan, Ai Huey; Tan, Chong Tin; Marras, Connie; Loh, Kwong Weng; Wye Ho, Niki Wai; Lim, Quan Hziung; Tan, Pei Wen; Lim, Chee Chean; Cheong, Yee Weai; Kong, Sik Thien; Schee, Jie Ping; Tan, Kean Hoong; Soo, Suet Ker; Vanderschaaf, Cheryl; Lai Heong Lew, Sara; Mahamad, Ummi Affah; Goh, Khean Jin; Yong, Hoi Sen; Lim, Shen-Yang

2015-01-01

Public knowledge regarding Parkinson's disease (PD) is important to facilitate good health-seeking behavior, but the literature on this topic is scarce. We aimed to explore the level of public knowledge regarding PD in a large multiethnic urban Asian cohort, and (as a secondary aim) in a smaller cohort of PD patients and caregivers. A Knowledge of PD Questionnaire (KPDQ) was developed and administered to members of the Malaysian general public, and to PD patients and caregivers. The KPDQ tests recognition of PD symptoms and general knowledge regarding PD. 1,258 members of the general public completed the KPDQ. Tremor was the most widely recognized symptom (recognized by 79.0% of respondents); however, 83.7% incorrectly believed that all PD patients experience tremor. Memory problem was the most widely recognized NMS. Overall, motor symptoms were better recognized than NMS. Common misperceptions were that there is a cure for PD (49.8%) and that PD is usually familial (41.4%). Female gender, Chinese ethnicity, tertiary education, healthcare-related work, and knowing someone with PD were independently associated with higher KPDQ scores. PD patients (n = 116) and caregivers (n = 135) demonstrated superior knowledge compared with the general public group, but one-third of them believed that PD is currently curable. This is the only study on public knowledge regarding PD in Asia. Important gaps in knowledge were evident, which could present a barrier to early diagnosis and appropriate treatment of PD. This highlights the need for targeted education campaigns and further research in this area.

Effects of physical exercise programs on cognitive function in Parkinson's disease patients: A systematic review of randomized controlled trials of the last 10 years.

PubMed

da Silva, Franciele Cascaes; Iop, Rodrigo da Rosa; de Oliveira, Laiana Cândido; Boll, Alice Mathea; de Alvarenga, José Gustavo Souza; Gutierres Filho, Paulo José Barbosa; de Melo, Lídia Mara Aguiar Bezerra; Xavier, André Junqueira; da Silva, Rudney

2018-01-01

Given the relative importance of cognitive impairment, there was considerable interest in identifying the cognitive profile of PD patients, in order to ensure specific and appropriate therapeutic interventions. To determine the effects of physical exercise programs on cognitive function in PD patients, compared with the control group. Medline, Cochrane, Scopus, PEDro and Web of Science (last searched in September 2016). Randomized clinical trials examining the effects of physical exercise programs and cognitive function in PD patients. Nine studies fulfilled the selection criteria and were included in this review. Characteristics of the publication, characteristics of the participants, test used for cognitive screening, cognitive domain assessed, tools used to assess cognitive function, characteristics of the experimental intervention, characteristics of the control group, mean results and standard deviation of function cognitive. The PEDro score was used to evaluate methodological quality. Most eligible studies showed good methodological quality based on the PEDro scale. Studies have shown that adapted tango for PD patients, cognitive training combined with motor training, and treadmill training promote the preservation or improvement of cognitive function in PD patients. The diversity of cognitive tests used to assess cognitive function and the high heterogeneity identified between the physical exercise programs. Physical exercise programs promote positive and significant effects on global cognitive function, processing speed, sustained attention and mental flexibility in PD patients, at a mild to moderate stage for patients with a 6-year clinical diagnosis of PD. However, treadmill training performed 3 times a week for about 60 minutes and for a period of 24 weeks produced larger improvements in cognition.

Ultrasound-detected subclinical inflammation was better reflected by the disease activity score (DAS-28) in patients with suspicion of inflammatory arthritis compared to established rheumatoid arthritis.

PubMed

Ciurtin, Coziana; Wyszynski, Karol; Clarke, Robert; Mouyis, Maria; Manson, Jessica; Marra, Giampiero

2016-10-01

Limited data are available about the ultrasound (US)-detected inflammatory features in patients with suspicion of inflammatory arthritis (S-IA) vs. established rheumatoid arthritis (RA). Our study aimed to assess if the presence of power Doppler (PD) can be predicted by a combination of clinical, laboratory and US parameters. We conducted a real-life, retrospective cohort study comparing clinical, laboratory and US parameters of 108 patients with established RA and 93 patients with S-IA. We propose a PD signal prediction model based on a beta-binomial distribution for PD variable using a mix of outcome measures. Patients with RA in clinical remission had significantly more active inflammation and erosions on US when compared with patients with S-IA with similar disease scores (p = 0.03 and p = 0.01, respectively); however, RA patients with different disease activity score (DAS-28) scores had similar PD scores (p = 0.058). The PD scores did not correlate with erosions (p = 0.38) or DAS-28 scores (p = 0.28) in RA patients, but they correlated with high disease activity in S-IA patients (p = 0.048). Subclinical inflammation is more common in patients with RA in clinical remission or with low disease activity than in patients with S-IA; therefore, US was more useful in assessing for true remission in RA rather than diagnosing IA in patients with low disease activity scores. This is the first study to propose a PD prediction model integrating several outcome measures in the two different groups of patients. Further research into validating this model can minimise the risk of underdiagnosing subclinical inflammation.

Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease.

PubMed

Ibanez, Laura; Dube, Umber; Davis, Albert A; Fernandez, Maria V; Budde, John; Cooper, Breanna; Diez-Fairen, Monica; Ortega-Cubero, Sara; Pastor, Pau; Perlmutter, Joel S; Cruchaga, Carlos; Benitez, Bruno A

2018-01-01

Background: The prevalence of dementia in Parkinson disease (PD) increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established. Objective: To assess the contribution of coding variants in Mendelian dementia-causing genes on the risk of developing PD and the effect on cognitive performance of PD patients. Methods: We analyzed the coding regions of the amyloid-beta precursor protein ( APP ), Presenilin 1 and 2 ( PSEN1, PSEN2 ), and Granulin ( GRN ) genes from 1,374 PD cases and 973 controls using pooled-DNA targeted sequence, human exome-chip and whole-exome sequencing (WES) data by single variant and gene base (SKAT-O and burden tests) analyses. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). The effect of coding variants in dementia-causing genes on cognitive performance was tested by multiple regression analysis adjusting for gender, disease duration, age at dementia assessment, study site and APOE carrier status. Results: Known AD pathogenic mutations in the PSEN1 (p.A79V) and PSEN2 (p.V148I) genes were found in 0.3% of all PD patients. There was a significant burden of rare, likely damaging variants in the GRN and PSEN1 genes in PD patients when compared with frequencies in the European population from the ExAC database. Multiple regression analysis revealed that PD patients carrying rare variants in the APP, PSEN1, PSEN2 , and GRN genes exhibit lower cognitive tests scores than non-carrier PD patients ( p = 2.0 × 10 -4 ), independent of age at PD diagnosis, age at evaluation, APOE status or recruitment site. Conclusions: Pathogenic mutations in the Alzheimer disease-causing genes ( PSEN1 and PSEN2) are found in sporadic PD patients. PD patients with cognitive decline carry rare variants in dementia-causing genes. Variants in genes causing Mendelian neurodegenerative diseases exhibit pleiotropic effects.

Impact of Depression on Hospitalization and Related Outcomes for Parkinson's Disease Patients: A Nationwide Inpatient Sample-Based Retrospective Study

PubMed Central

Makani, Ramkrishna; Mansuri, Zeeshan; Patel, Upenkumar; Desai, Rupak; Chopra, Amit

2017-01-01

Background Major Depressive Disorder (MDD) is a common comorbidity that significantly affects the quality of life and disease outcomes in Parkinson’s disease (PD) patients. No studies have been conducted to our knowledge to address the health care utilization and its outcomes in these patients. The aim of this study is to analyze and discern the differences in the hospitalization outcomes, comorbid conditions, and utilization of procedures in PD patients versus patients with comorbid MDD. Methods We used the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project from year’s 2010-2014. We identified PD and MDD as a primary and secondary diagnosis respectively using validated International Classification of Diseases, 9th Revision, and Clinical Modification codes. Pearson’s chi-square test and independent sample T-test were used for categorical data and continuous data, respectively. All statistical analysis was done by SPSS 22.0 in this study. Results Extensive analysis was performed on 63,912 patients with PD and 1445 patients with PD having MDD. Patients with comorbid depression had three times greater chances of disposition to acute care hospital (3.1% vs. 1.1%, p < 0.001). Median length of hospitalization was higher in Parkinson’s patients with depression (5.85 vs. 4.08 days; p < 0.001) though the median cost of hospitalization was low ($ 31,039 vs. $ 39,464; p < 0.001). This could be because therapeutic procedures performed during the hospitalization were lower in Parkinson’s patients with depression (0.53 vs. 0.89, p < 0.001). Utilization of Deep Brain Stimulation (DBS) was lower in Parkinson’s patients with depression (9.4% vs. 25.6%, p < 0.001). In­-hospital mortality was significantly higher in Parkinson’s patients with depression (1.4% vs. 1.1%; p < 0.001). Conclusion Our study establishes the negative impact of depression in PD with regards to hospitalization-related outcomes including the illness severity, comorbid conditions, risk of mortality, utilization of diagnostic and therapeutic procedures, the length of stay and disposition as compared to PD without depression. PMID:29142796

Development and Retrospective Clinical Assessment of a Patient-Specific Closed-Form Integro-Differential Equation Model of Plasma Dilution.

PubMed

Atlas, Glen; Li, John K-J; Amin, Shawn; Hahn, Robert G

2017-01-01

A closed-form integro-differential equation (IDE) model of plasma dilution (PD) has been derived which represents both the intravenous (IV) infusion of crystalloid and the postinfusion period. Specifically, PD is mathematically represented using a combination of constant ratio, differential, and integral components. Furthermore, this model has successfully been applied to preexisting data, from a prior human study, in which crystalloid was infused for a period of 30 minutes at the beginning of thyroid surgery. Using Euler's formula and a Laplace transform solution to the IDE, patients could be divided into two distinct groups based on their response to PD during the infusion period. Explicitly, Group 1 patients had an infusion-based PD response which was modeled using an exponentially decaying hyperbolic sine function, whereas Group 2 patients had an infusion-based PD response which was modeled using an exponentially decaying trigonometric sine function. Both Group 1 and Group 2 patients had postinfusion PD responses which were modeled using the same combination of hyperbolic sine and hyperbolic cosine functions. Statistically significant differences, between Groups 1 and 2, were noted with respect to the area under their PD curves during both the infusion and postinfusion periods. Specifically, Group 2 patients exhibited a response to PD which was most likely consistent with a preoperative hypovolemia. Overall, this IDE model of PD appears to be highly "adaptable" and successfully fits clinically-obtained human data on a patient-specific basis, during both the infusion and postinfusion periods. In addition, patient-specific IDE modeling of PD may be a useful adjunct in perioperative fluid management and in assessing clinical volume kinetics, of crystalloid solutions, in real time.

Development and Retrospective Clinical Assessment of a Patient-Specific Closed-Form Integro-Differential Equation Model of Plasma Dilution

PubMed Central

Atlas, Glen; Li, John K-J; Amin, Shawn; Hahn, Robert G

2017-01-01

A closed-form integro-differential equation (IDE) model of plasma dilution (PD) has been derived which represents both the intravenous (IV) infusion of crystalloid and the postinfusion period. Specifically, PD is mathematically represented using a combination of constant ratio, differential, and integral components. Furthermore, this model has successfully been applied to preexisting data, from a prior human study, in which crystalloid was infused for a period of 30 minutes at the beginning of thyroid surgery. Using Euler’s formula and a Laplace transform solution to the IDE, patients could be divided into two distinct groups based on their response to PD during the infusion period. Explicitly, Group 1 patients had an infusion-based PD response which was modeled using an exponentially decaying hyperbolic sine function, whereas Group 2 patients had an infusion-based PD response which was modeled using an exponentially decaying trigonometric sine function. Both Group 1 and Group 2 patients had postinfusion PD responses which were modeled using the same combination of hyperbolic sine and hyperbolic cosine functions. Statistically significant differences, between Groups 1 and 2, were noted with respect to the area under their PD curves during both the infusion and postinfusion periods. Specifically, Group 2 patients exhibited a response to PD which was most likely consistent with a preoperative hypovolemia. Overall, this IDE model of PD appears to be highly “adaptable” and successfully fits clinically-obtained human data on a patient-specific basis, during both the infusion and postinfusion periods. In addition, patient-specific IDE modeling of PD may be a useful adjunct in perioperative fluid management and in assessing clinical volume kinetics, of crystalloid solutions, in real time. PMID:29123436

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among malaria patients in Upper Myanmar.

PubMed

Lee, Jinyoung; Kim, Tae Im; Kang, Jung-Mi; Jun, Hojong; Lê, Hương Giang; Thái, Thị Lam; Sohn, Woon-Mok; Myint, Moe Kyaw; Lin, Khin; Kim, Tong-Soo; Na, Byoung-Kuk

2018-03-16

Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is one of the most common X-linked recessive hereditary disorders in the world. Primaquine (PQ) has been used for radical cure of P. vivax to prevent relapse. Recently, it is also used to reduce P. falciparum gametocyte carriage to block transmission. However, PQ metabolites oxidize hemoglobin and generate excessive reactive oxygen species which can trigger acute hemolytic anemia in malaria patients with inherited G6PD deficiency. A total of 252 blood samples collected from malaria patients in Myanmar were used in this study. G6PD variant was analysed by a multiplex allele specific PCR kit, DiaPlexC™ G6PD Genotyping Kit [Asian type]. The accuracy of the multiplex allele specific PCR was confirmed by sequencing analysis. Prevalence and distribution of G6PD variants in 252 malaria patients in Myanmar were analysed. Six different types of G6PD allelic variants were identified in 50 (7 females and 43 males) malaria patients. The predominant variant was Mahidol (68%, 34/50), of which 91.2% (31/34) and 8.8% (3/34) were males and females, respectively. Other G6PD variants including Kaiping (18%, 9/50), Viangchan (6%, 3/50), Mediterranean (4%, 2/50), Union (2%, 1/50) and Canton (2%, 1/50) were also observed. Results of this study suggest that more concern for proper and safe use of PQ as a radical cure of malaria in Myanmar is needed by combining G6PD deficiency test before PQ prescription. Establishment of a follow-up system to monitor potential PQ toxicity in malaria patients who are given PQ is also required.

G6PD Deficiency Does Not Enhance Susceptibility for Acquiring Helicobacter pylori Infection in Sardinian Patients

PubMed Central

Dore, Maria Pina; Marras, Giuseppina; Rocchi, Chiara; Soro, Sara

2016-01-01

Background Subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more susceptible to infections due to impaired leukocyte bactericidal activity. The disorder is common in the Mediterranean area. The aim of this study was to investigate whether G6PD deficiency may be a risk factor for acquiring H. pylori infection. Methods We performed a retrospective study. Data from clinical records of 6565 patients (2278 men and 4287 women, median age 51, range 7‒94) who underwent upper endoscopy between 2002 and 2014 were collected. H. pylori status, assessed by histology plus rapid urease test or 13C-urea breath test, and G6PD status were also reported. A multiple logistic regression model was used to investigate the association between G6PD deficiency and H. pylori infection. Results Enzyme deficiency was detected in 12% (789/6565) of the entire cohort, and more specifically in 8.3% of men and in 14.0% of women. Overall, the proportion of patients positive for H. pylori was 50.6% and 51.5% among G6PD deficient and non-deficient patients (χ² = 0.271; p = 0.315). Moreover, among G6PD-deficient and normal patients the frequency of previous H. pylori infection was similar. After adjustment for age and gender the risk for acquiring H. pylori infection was similar in G6PD-deficient and normal patients. Only age was a strong statistically significant risk predictor. Conclusions These results demonstrate for the first time that G6PD deficiency does not enhance patients’ susceptibility to acquire H. pylori infection in Sardinia. PMID:27467818

Screening for impulse control symptoms in patients with de novo Parkinson disease: a case-control study.

PubMed

Weintraub, Daniel; Papay, Kimberly; Siderowf, Andrew

2013-01-08

To determine the frequency and correlates of impulse control and related behavior symptoms in patients with de novo, untreated Parkinson disease (PD) and healthy controls (HCs). The Parkinson's Progression Markers Initiative is an international, multisite, case-control clinical study conducted at 21 academic movement disorders centers. Participants were recently diagnosed, untreated PD patients (n = 168) and HCs (n = 143). The outcome measures were presence of current impulse control and related behavior symptoms based on recommended cutoff points for the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP)-Short Form. There were 311 participants with complete QUIP data. Frequencies of impulse control and related behavior symptoms for patients with PD vs HCs were as follows: gambling (1.2% vs. 0.7%), buying (3.0% vs. 2.1%), sexual behavior (4.2% vs. 3.5%), eating (7.1% vs. 10.5%), punding (4.8% vs. 2.1%), hobbyism (5.4% vs. 11.9%), walkabout (0.6% vs. 0.7%), and any impulse control or related behavior (18.5% vs. 20.3%). In multivariable models, a diagnosis of PD was not associated with symptoms of any impulse control or related behavior (p ≥ 0.10 in all cases). PD itself does not seem to confer an increased risk for development of impulse control or related behavior symptoms, which further reinforces the reported association between PD medications and impulse control disorders in PD. Given that approximately 20% of patients with newly diagnosed PD report some impulse control or related behavior symptoms, long-term follow-up is needed to determine whether such patients are at increased risk for impulse control disorder development once PD medications are initiated.

Global differences in dialysis modality mix: the role of patient characteristics, macroeconomics and renal service indicators.

PubMed

van de Luijtgaarden, Moniek W M; Jager, Kitty J; Stel, Vianda S; Kramer, Anneke; Cusumano, Ana; Elliott, Robert F; Geue, Claudia; MacLeod, Alison M; Stengel, Benedicte; Covic, Adrian; Caskey, Fergus J

2013-05-01

An increase in the dialysis programme expenditure is expected in most countries given the continued rise in the number of people with end-stage renal disease (ESRD) globally. Since chronic peritoneal dialysis (PD) therapy is relatively less expensive compared with haemodialysis (HD) and because there is no survival difference between PD and HD, identifying factors associated with PD use is important. Incidence counts for the years 2003-05 were available from 36 countries worldwide. We studied associations of population characteristics, macroeconomic factors and renal service indicators with the percentage of patients on PD at Day 91 after starting dialysis. With linear regression models, we obtained relative risks (RRs) with 95% confidence intervals (CIs). The median percentage of incident patients on PD was 12% (interquartile range: 7-26%). Determinants independently associated with lower percentages of patients on PD were as follows: patients with diabetic kidney disease (per 5% increase) (RR 0.93; 95% CI 0.89-0.97), health expenditure as % gross domestic product (per 1% increase) (RR 0.93; 95% CI 0.87-0.98), private-for-profit share of HD facilities (per 1% increase) (RR 0.996; 95% CI 0.99-1.00; P = 0.04), costs of PD consumables relative to staffing (per 0.1 increase) (RR 0.97; 95% CI 0.95-0.99). The factors associated with a lower percentage of patients on PD include higher diabetes prevalence, higher healthcare expenditures, larger share of private-for-profit centres and higher costs of PD consumables relative to staffing. Whether dialysis modality mix can be influenced by changing healthcare organization and funding requires additional studies.

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data.

PubMed

Fengler, S; Roeske, S; Heber, I; Reetz, K; Schulz, J B; Riedel, O; Wittchen, H U; Storch, A; Linse, K; Baudrexel, S; Hilker, R; Mollenhauer, B; Witt, K; Schmidt, N; Balzer-Geldsetzer, M; Dams, J; Dodel, R; Gräber, S; Pilotto, A; Petrelli, A; Fünkele, S; Kassubek, J; Kalbe, E

2016-08-01

Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered. The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates. Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis. Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.

Association between keeping home records of catheter exit-site and incidence of peritoneal dialysis-related infections.

PubMed

Iida, Hidekazu; Kurita, Noriaki; Fujimoto, Shino; Kamijo, Yuka; Ishibashi, Yoshitaka; Fukuma, Shingo; Fukuhara, Shunichi

2018-04-01

To prevent peritoneal dialysis (PD)-related infection, components of self-catheter care have been emphasized. However, studies on the effectiveness of home recording for the prevention of PD-related infections are limited. This study aimed to examine the association between keeping home records of catheter exit site and incidence of PD-related infections. Home record books were submitted by patients undergoing PD. The proportion of days on which exit-site home recording was carried out for 120 days (0-100%) was obtained. The patients were divided into the frequent home recording group (≥ 40.5%; median value) and the infrequent home recording group (< 40.5%). The associations between the recording group and the incidence rate ratios (IRRs) of PD-related infections were estimated via negative binomial regression models. A total of 67 patients participated in this study (mean age, 66.7 years). The incidence rates for exit-site infection, tunnel infection, and peritonitis were 0.42, 0.22, and 0.06 times/patient-year, respectively. The IRRs of the frequent versus infrequent home recording groups for PD-related infection were 1.58 (95% confidence interval [CI], 0.72-3.46) in the univariate analysis and 1.49 (95% CI, 0.65-3.42) in the multivariate analysis. The IRRs of the frequent versus infrequent home recording groups for composite of surgery to create a new exit site and removal of PD catheter were 0.55 (95% CI, 0.78-3.88) and 0.35 (95% CI, 0.06-1.99), respectively. This study could not prove that keeping home records of patients' catheter exit site is associated with a lower incidence of PD-related infections.

The value of power Doppler ultrasound in patients with rheumatoid arthritis in clinical remission: Reclassifying disease activity?

PubMed

Vergara, Facundo; Ruta, Santiago; Rosa, Javier; Marín, Josefina; García-Mónaco, Ricardo; Soriano, Enrique R

2017-03-18

The aim of the present study was to describe the ultrasound (US) findings in patients with rheumatoid arthritis (RA) in clinical remission, and to evaluate the ability of power Doppler (PD) US to reclassify disease activity in these patients. We included consecutive patients with RA according to 2010 American College of Rheumatology/European League Against Rheumatism criteria, who were in clinical remission by the Disease Activity Score (DAS28<2.6). Twenty joints of both hands were assessed by US. PD signal was evaluated on a semi-quantitative scale from 0 to 3. Three different US-modified DAS28 (US-DAS28) were constructed, replacing the clinical swollen joint count by the PD US joint count using PD score ≥1, ≥2 or ≥3, respectively. Eighty-six patients were included. Twenty-three (26.7%) patients had at least one joint with abnormal US-positive PD signal. Thirteen percent of patients were reclassified to low disease activity by applying the US-DAS28 when joints were considered active with a PD signal ≥1; 12%, when a PD signal ≥2 was considered, and 2% of the patients were reclassified when a PD score of 3 was considered. No patients were reclassified to a level of moderate or high activity applying US-DAS28. Although around a quarter of patients with RA in clinical remission showed PD US features indicating residual activity, only a small percentage were reclassified to a state of low activity and none to a level of moderate or high activity, applying the proposed US-DAS28. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

The Role of Intrinsic Pathway in Apoptosis Activation and Progression in Peyronie's Disease

PubMed Central

Loreto, Carla; Caltabiano, Rosario; Vespasiani, Giuseppe; Castorina, Sergio; Ralph, David J.; Musumeci, Giuseppe; Djinovic, Rados; Sansalone, Salvatore

2014-01-01

Peyronie's disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes, and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplastic bone tissue. Apoptosis occurs in stabilized PD plaques and is partly induced by the intrinsic pathway. PMID:25197653

Parkinson Patients’ Initial Trust in Avatars: Theory and Evidence

PubMed Central

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson’s disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients’ interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research. PMID:27820864

Increasing hip fractures in patients receiving hemodialysis and peritoneal dialysis.

PubMed

Mathew, Anna T; Hazzan, Azzour; Jhaveri, Kenar D; Block, Geoffrey A; Chidella, Shailaja; Rosen, Lisa; Wagner, John; Fishbane, Steve

2014-01-01

Dialysis patients are at increased risk for hip fractures. Because changes in treatment of metabolic bone disease in this population may have impacted bone fragility, this study aims to analyze the longitudinal risk for fractures in hemodialysis (HD) and peritoneal dialysis (PD) patients. Using the United States Renal Data System database from 1992 to 2009, the temporal trend in hip fractures requiring hospitalization was analyzed using an overdispersed Poisson regression model. Generalized Estimating Equations were used to assess the adjusted effect of dialysis modality on hip fractures. 842,028 HD and 87,086 PD patients were included. There was a significant temporal increase in hip fractures in both HD and PD with stabilization of rates after 2005. With stratification, the increase in fractures occurred in patients who were white and over 65 years of age. In adjusted analyses, HD patients had 1.6 times greater odds of hip fracture than PD patients (OR 1.60 95% CI 1.52, 1.68, p < 0.001). In contrast to the declining hip fracture rates in the general population, we identified a temporal rise in incidence of hip fractures in HD and PD patients. HD patients were at a higher risk for hip fractures than PD patients after adjustment for recognized bone fragility risk factors. The increase in fracture rate over time was limited to older white patients in both HD and PD, the demographics being consistent with osteoporosis risk. Further research is indicated to better understand the longitudinal trend in hip fractures and the discordance between HD and PD. © 2014 S. Karger AG, Basel.

Genomics of NSCLC patients both affirm PD-L1 expression and predict their clinical responses to anti-PD-1 immunotherapy.

PubMed

Brogden, Kim A; Parashar, Deepak; Hallier, Andrea R; Braun, Terry; Qian, Fang; Rizvi, Naiyer A; Bossler, Aaron D; Milhem, Mohammed M; Chan, Timothy A; Abbasi, Taher; Vali, Shireen

2018-02-27

Programmed Death Ligand 1 (PD-L1) is a co-stimulatory and immune checkpoint protein. PD-L1 expression in non-small cell lung cancers (NSCLC) is a hallmark of adaptive resistance and its expression is often used to predict the outcome of Programmed Death 1 (PD-1) and PD-L1 immunotherapy treatments. However, clinical benefits do not occur in all patients and new approaches are needed to assist in selecting patients for PD-1 or PD-L1 immunotherapies. Here, we hypothesized that patient tumor cell genomics influenced cell signaling and expression of PD-L1, chemokines, and immunosuppressive molecules and these profiles could be used to predict patient clinical responses. We used a recent dataset from NSCLC patients treated with pembrolizumab. Deleterious gene mutational profiles in patient exomes were identified and annotated into a cancer network to create NSCLC patient-specific predictive computational simulation models. Validation checks were performed on the cancer network, simulation model predictions, and PD-1 match rates between patient-specific predicted and clinical responses. Expression profiles of these 24 chemokines and immunosuppressive molecules were used to identify patients who would or would not respond to PD-1 immunotherapy. PD-L1 expression alone was not sufficient to predict which patients would or would not respond to PD-1 immunotherapy. Adding chemokine and immunosuppressive molecule expression profiles allowed patient models to achieve a greater than 85.0% predictive correlation among predicted and reported patient clinical responses. Our results suggested that chemokine and immunosuppressive molecule expression profiles can be used to accurately predict clinical responses thus differentiating among patients who would and would not benefit from PD-1 or PD-L1 immunotherapies.

Interaction effect of psychological distress and asthma control on productivity loss?

PubMed

Moullec, Grégory; FitzGerald, J Mark; Rousseau, Roxanne; Chen, Wenjia; Sadatsafavi, Mohsen

2015-06-01

Little is known about the potential synergistic effect of comorbid psychological distress (PD) and uncontrolled asthma (UA) on productivity loss. We estimated the productivity loss associated with the combination of these two potentially preventable conditions in employed adults with asthma. A population-based random sample of 300 adults with asthma in British Columbia, Canada, was prospectively recruited between Dec 2010 and Aug 2012. PD and productivity loss due to absenteeism and presenteeism was measured using validated instruments, and asthma control was ascertained using 2010 Global Initiative for Asthma management strategy. We used two-part regression models to study the contribution of UA and PD to productivity loss. Compared with reference group (controlled asthma (CA)+noPD), those with UA+noPD had CAD$286 (95%CI $276-297) weekly productivity loss, and those with CA+PD had CAD$465 ($445-485). Those with UA+PD had CAD$449 (437-462) in productivity loss. There was no significant interaction effect of PD with asthma control levels on productivity loss (p=0.22). In patients without PD, uncontrolled asthma was associated with a higher productivity loss than controlled asthma, but this was not the case in patients with PD. This finding can be explained by the fact that the contribution of PD to productivity loss is so large that there is no room for synergy with asthma control. Future studies should assess the impact of interventions that modify PD in patients with asthma. Copyright ©ERS 2015.

Increased arterial stiffness parameters in panic disorder patients in long term treatment period.

PubMed

Yanartas, Omer; Sunbul, Murat; Senkal, Zeynep; Durmus, Erdal; Kivrak, Tarik; Subasi, Nilufer; Karaer, Gulhan; Ergun, Serhat; Sari, Ibrahim; Sayar, Kemal

2016-01-01

The relationship between mental stress and cardiovascular disease has been shown in several studies. Panic disorder (PD) is also associated with cardiovascular disease due to increased risk of myocardial infarction. The aim of this study is to evaluate the association between arterial stiffness parameters and depression/anxiety scores in patients with PD. The study population consisted of 25 patients with PD and 25 age-sex-matched healthy controls. Depression and anxiety levels were evaluated by Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. Determination of arterial stiffness parameters was conducted using a Mobil-O-Graph arteriograph system that detected signals from the brachial artery. While baseline characteristics were similar between two groups, BDI and BAI scores were significantly higher in patients with PD (p < 0.005). The pulse wave velocity (PWV) and Augmentation Index (AIx) were also significantly higher in patients with PD (p = 0.001, p = 0.006). There was a moderate correlation between PWV and AIx with BAI scores (r = 0.442, p = 0.001, r = 0.441, p = 0.001). AIx was also positively correlated with BDI scores (r = 0.415, p = 0.03). We demonstrated a significant relationship between arterial stiffness parameters and anxiety/depression scores in patients with PD who receive antidepressant treatment.

Effect of cognitive and motor tasks on postural stability in Parkinson's disease: a posturographic study.

PubMed

Marchese, Roberta; Bove, Marco; Abbruzzese, Giovanni

2003-06-01

To analyse the effect of concomitant cognitive or motor task performance on balance control in Parkinson's disease (PD), we performed a posturographic study in 24 PD patients and in 20 sex- and age-matched control subjects. Postural sway was measured with eyes open (EO) and eyes closed (EC) during quiet stance and during performance of calculation or motor sequence of thumb opposition to the other fingers. No difference of centre of foot pressure (COP) parameters was observed during quiet standing (either EO or EC) between patients and controls, but visual deprivation induced in both groups a worsening of postural stability. COP area was significantly increased in PD patients during dual task performance, whereas no difference of COP path and x-y axes was observed. The effects induced by the performance of cognitive or motor task were significantly more evident in PD patients with clinical evidence of postural instability (presence of prior falls in the history). This study demonstrates that dual task interference on postural control can be observed in PD patients during performance of cognitive as well as motor tasks. The balance deterioration during dual task performance was significantly enhanced in patients with history of prior falls. These findings have some implications for the strategies to be used in reducing the risk of fall in PD. Copyright 2003 Movement Disorder Society

Impairment of work productivity in panic disorder patients.

PubMed

Lee Park, Yu; Kim, Won; Chae, Jeong-Ho; Seo Oh, Kang; Frick, Kevin D; Woo, Jong-Min

2014-03-01

Panic disorder (PD) has a critical impact on productivity at the workplace. This study aimed to identify the lost productivity time (LPT) for patients with PD. It also assessed change in LPT for patients with PD after 12 weeks of treatment with Selective Serotonin Reuptake Inhibitors (SSRIs), compared with healthy controls. Working patients diagnosed with PD without other major medical or psychiatric illness were enrolled at outpatient psychiatric clinics (N=108). Age and sex-matched healthy controls were recruited through advertisement (N=108). Health and productivity, PD symptoms, and depressive symptoms were assessed using the Korean version of the World Health Organization's Health and Work Performance Questionnaire (HPQ), the Panic Disorder Severity Scale (PDSS), and the Hamilton Rating Scales for Depression (HAM-D), respectively at baseline, week 4, and week 12. At baseline, the PD group showed significantly higher LPT compared to the control group (103.02 vs. 47.28h in the past 4 weeks). After 12 weeks of treatment, the PD group displayed significant clinical improvement as well as improved productivity with a marked reduction in LPT. Among the patients who completed the treatment, LPT due to PD was reduced from 104.38 to 55.15h in the past 4 weeks. There may be selection bias due to case-control study design. These data suggest that, after the treatment, there was significant improvement in clinical symptoms, and that productivity loss due to PD was almost entirely recovered to the level of healthy controls after 12 weeks of psychiatric outpatient treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Observations on Sleep-Disordered Breathing in Idiopathic Parkinson’s Disease

PubMed Central

Valko, Philipp O.; Hauser, Sabrina; Sommerauer, Michael; Werth, Esther; Baumann, Christian R.

2014-01-01

Background This study has two main goals: 1.) to determine the potential influence of dopaminergic drugs on sleep-disordered breathing (SDB) in Parkinson’s disease (PD) and 2.) to elucidate whether NREM and REM sleep differentially impact SDB severity in PD. Methods Retrospective clinical and polysomnographic study of 119 consecutive PD patients and comparison with age-, sex- and apnea-hypopnea-index-matched controls. Results SDB was diagnosed in 57 PD patients (48%). Apnea-hypopnea index was significantly higher in PD patients with central SDB predominance (n = 7; 39.3±16.7/h) than obstructive SDB predominance (n = 50; 20.9±16.8/h; p = 0.003). All PD patients with central SDB predominance appeared to be treated with both levodopa and dopamine agonists, whereas only 56% of those with obstructive SDB predominance were on this combined treatment (p = 0.03). In the whole PD group with SDB (n = 57), we observed a significant decrease of apnea-hypopnea index from NREM to REM sleep (p = 0.02), while controls revealed the opposite tendency. However, only the PD subgroup with SDB and treatment with dopamine agonists showed this phenomenon, while those without dopamine agonists had a similar NREM/REM pattern as controls. Conclusions Our findings suggest an ambiguous impact of dopamine agonists on SDB. Medication with dopamine agonists seems to enhance the risk of central SDB predominance. Loss of normal muscle atonia may be responsible for decreased SDB severity during REM sleep in PD patients with dopamine agonists. PMID:24968233

Early Peritonitis in a Large Peritoneal Dialysis Provider System in Colombia.

PubMed

Vargas, Edgar; Blake, Peter G; Sanabria, Mauricio; Bunch, Alfonso; López, Patricia; Vesga, Jasmín; Buitrago, Alberto; Astudillo, Kindar; Devia, Martha; Sánchez, Ricardo

♦ BACKGROUND: Peritonitis is the most important complication of peritoneal dialysis (PD), and early peritonitis rate is predictive of the subsequent course on PD. Our aim was to calculate the early peritonitis rate and to identify characteristics and predisposing factors in a large nationwide PD provider network in Colombia. ♦ METHODS: This was a historical observational cohort study of all adult patients starting PD between January 1, 2012, and December 31, 2013, in 49 renal facilities in the Renal Therapy Services in Colombia. We studied the peritonitis rate in the first 90 days of treatment, its causative micro-organisms, its predictors and its variation with time on PD and between individual facilities. ♦ RESULTS: A total of 3,525 patients initiated PD, with 176 episodes of peritonitis during 752 patient-years of follow-up for a rate of 0.23 episodes per patient year equivalent to 1 every 52 months. In 41 of 49 units, the rate was better than 1 per 33 months, and in 45, it was better than 1 per 24 months. Peritonitis rates did not differ with age, ethnicity, socioeconomic status, or PD modality. We identified high incidence risk periods at 2 to 5 weeks after initiation of PD and again at 10 to 12 weeks. ♦ CONCLUSION: An excellent peritonitis rate was achieved across a large nationwide network. This occurred in the context of high nationwide PD utilization and despite high rates of socioeconomic deprivation. We propose that a key factor in achieving this was a standardized approach to management of patients. Copyright © 2017 International Society for Peritoneal Dialysis.

The Association Between PD-L1 Expression and the Clinical Outcomes to Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

PubMed Central

Shin, Su-Jin; Jeon, Yoon Kyung; Cho, Yong Mee; Lee, Jae-Lyun; Chung, Doo Hyun; Park, Ji Young

2015-01-01

Background. Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are used as the first-line treatment for patients with metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising therapy for renal cell carcinoma. However, the expression pattern and prognostic implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF-TKI remain unclear. Patients and Methods. PD-L1 and PD-L2 expression in tumor cells and the quantities of PD-1+ tumor-infiltrating lymphocytes were immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and their associations with VEGF-TKI responsiveness and clinical outcome were analyzed. Results. PD-L1 immunopositivity was observed in 17.6% and significantly associated with a high International Society of Urological Pathology grade (p = .031) and sarcomatoid features (p = .014). PD-L2 immunopositivity was observed in 39.6% and was not associated with any of the assessed clinicopathological variables. PD-L1-positive cases showed poor VEGF-TKI responsiveness (p = .012) compared with PD-L1-negative cases. In univariate survival analysis, PD-L1 immunopositivity was significantly associated with shorter overall survival (OS) (p = .037) and progression-free survival (PFS) (p = .043). Multivariate survival analysis revealed that PD-L1 expression was independently associated with poor OS (p = .038) and PFS (p = .013) in addition to tumor necrosis (p = .006; p = .029, respectively) and Memorial Sloan Kettering Cancer Center score (p = .018; p = .032, respectively). PD-L2 expression was neither associated with VEGF-TKI responsiveness nor patients’ outcome. Conclusion. PD-L1 expression was significantly related to lack of VEGF-TKI responsiveness and independently associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD-L1 may have a predictive and prognostic value for determining the value of VEGF-TKI treatment in patients with mCCRCC. Implications for Practice: Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are essential for the treatment of metastatic renal cell carcinoma patients, but the treatment suffers from a lack of predictive markers. This study demonstrates that PD-L1 expression is a predictor for unfavorable response to VEGF-TKI and a prognostic indicator for poor overall survival and progression-free survival in patients with metastatic clear cell renal cell carcinoma receiving VEGF-TKI. PMID:26424759

The Evolution of REM Sleep Behavior Disorder in Early Parkinson Disease.

PubMed

Sixel-Döring, Friederike; Zimmermann, Johannes; Wegener, Andrea; Mollenhauer, Brit; Trenkwalder, Claudia

2016-09-01

To investigate the development of REM sleep behavior disorder (RBD) and REM sleep behavioral events (RBE) not yet fulfilling diagnostic criteria for RBD as markers for neurodegeneration in a cohort of Parkinson disease (PD) patients between their de novo baseline assessment and two-year follow-up in comparison to healthy controls (HC). Clinically confirmed PD patients and HC with video-supported polysomnography (vPSG) data at baseline were re-investigated after two years. Diagnostic scoring for RBE and RBD was performed in both groups and related to baseline findings. One hundred thirteen PD patients and 102 healthy controls (HC) were included in the study. Within two years, the overall occurrence of behaviors during REM sleep in PD patients increased from 50% to 63% (P = 0.02). RBD increased from 25% to 43% (P < 0.001). Eleven of 29 (38%) RBE positive PD patients and 10/56 (18%) patients with normal REM sleep at baseline converted to RBD. In HC, the occurrence of any REM behavior increased from 17% to 20% (n.s.). RBD increased from 2% to 4% (n.s.). One of 15 (7%) RBE positive HC and 1/85 (1%) HC with normal REM at baseline converted to RBD. RBD increased significantly in PD patients from the de novo state to two-year follow-up. We propose RBE being named "prodromal RBD" as it may follow a continuous evolution in PD possibly similar to the spreading of Lewy bodies in PD patients. RBD itself was shown as a robust and stable marker of early PD. © 2016 Associated Professional Sleep Societies, LLC.

Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson's disease.

PubMed

Zhao, Na; Xiao, Jianqiu; Zheng, Zhiyong; Fei, Guoqiang; Zhang, Feng; Jin, Lirong; Zhong, Chunjiu

2015-04-01

Our previous studies have demonstrated that ceruloplasmin (CP) dysmetabolism is correlated with Parkinson's disease (PD). However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene (both promoter and coding regions) were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms (SNPs). High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/iron metabolism. The frequencies of eight SNPs (one intronic SNP and seven promoter SNPs of the CP gene) and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.

Nutritional status, fecal elastase-1, and 13C-labeled mixed triglyceride breath test in the long-term after pancreaticoduodenectomy.

PubMed

Muniz, Cinara Knychala; dos Santos, José Sebastião; Pfrimer, Karina; Ferrioli, Eduardo; Kemp, Rafael; Marchini, Júlio Sérgio; Cunha, Selma Freire

2014-04-01

This study aimed to compare the body composition, dietary intake and serum levels of vitamins and minerals, and exocrine pancreatic function in patients late after pancreaticoduodenectomy (PD) and healthy subjects. Fifteen patients (PD group) who had undergone PD over 1 year before the study and 15 health volunteers (control group) were included in the study. All volunteers underwent dietary intake evaluation, body composition, laboratory data, exocrine pancreatic function by elastase-1, and carbon (C )-labeled triglycerides in breath tests. The PD group subjects also underwent upper gastrointestinal endoscopy and small intestinal bacterial overgrowth analysis. Nutrient intake was adequate, and there were no differences in body mass index and mineral serum levels between the groups. The PD group showed lower serum levels of retinol, α-tocopherol, and ascorbic acid. Small intestinal bacterial overgrowth occurred in 39% of the patients. Fecal elastase-1 was lower in the PD group. The PD group had a higher C peak time; the cumulative label C recovery in 7 hours was similar in both groups. Fecal elastase-1 decreased, and the excretion of C in breath was similar to healthy controls. Although the data point toward an adaptation in the absorptive capacity of fats, A, C, and E hypovitaminosis indicate that some absorptive insufficiency persists late after PD.

What motivates Parkinson's disease patients to enter clinical trials?

PubMed

Valadas, Anabela; Coelho, Miguel; Mestre, Tiago; Guedes, Leonor Correia; Finisterra, Maria; Noronha, Ana; Rosa, Mário M; Sampaio, Cristina; Ferreira, Joaquim J

2011-11-01

Limited data is available regarding motivations and concerns of Parkinson's disease (PD) patients when participating in clinical trials (CTs). Knowledge of these factors may improve the recruitment and quality of future trials. To assess the motivations and concerns of PD patients concerning participation in CTs and to evaluate the extent to which patients understand informed consent materials and placebo effect concept. Cross-sectional study in PD patients enrolled in CTs between 2002 and 2007. Two questionnaires designed for placebo-controlled and active-controlled studies were mailed to patients. From the 93/127 replied questionnaires (response rate: 73.2%) 91 were evaluable. Fifty-nine percent of the participants were women with a mean age of 66.8 years. The main reasons for participating in CTs were to help the advance of science (63.7%), to gain access to a better treatment (56.0%), and to benefit others (51.6%). Risk of adverse events (49.5%) and negative effects of treatment (35.2%) were the major concerns. Ninety percent reported they had understood the informed consent. Of 80 patients included in placebo-controlled studies, 63.9% understood the placebo effect concept. Globally, 66% of patients would participate in another CT and 41.6% in a placebo-controlled trial. The main motivations of PD patients to participate in CTs were the benefit to the patient himself and to others. The major concern was safety. PD patients understood the informed consent, but more educational efforts must be made to explain the placebo effect. Most PD patients were very positive toward CTs and would participate in another trial. Copyright © 2011 Elsevier Ltd. All rights reserved.

Is EQ-5D a valid quality of life instrument in patients with Parkinson's disease? A study in Singapore.

PubMed

Luo, Nan; Low, Serena; Lau, Puay-Ngoh; Au, Wing-Lok; Tan, Louis C S

2009-06-01

The purpose of the present study was to evaluate the validity of the EQ-5D in patients with Parkinson's disease (PD) in Singapore. In a cross-sectional survey, patients with PD completed English or Chinese version of the EQ-5D, the 8-item Parkinson's disease questionnaire (PDQ-8), and questions assessing socio-demographic and health characteristics. Clinical data were retrieved from patients' medical records. The validity of the EQ-5D was assessed by testing a-priori hypotheses relating the EQ-5D to the PDQ-8 and clinical data. Two hundred and eight PD patients (English speaking: 135) participated in the study. Spearman correlation coefficients between the EQ-5D and PDQ-8 ranged from 0.25 to 0.75 for English-speaking patients and from 0.16 to 0.67 for Chinese-speaking patients. By and large, the EQ-5D scores were weakly or moderately correlated with Hoehn and Yahr stage (correlation coefficients: 0.05 to 0.43), Schwab and England Activities of Daily Living score (correlation coefficients: 0.10 to 0.60), and duration of PD (correlation coefficients: 0.16 to 0.43). The EQ-5D index scores for patients with dyskinesia or "wearing off" periods were significantly lower than those without these problems. The EQ-5D Visual Analog Scale (EQ-VAS) scores also differed for English-speaking patients with deferring dyskinesia, "wearing off" periods, or health transition status; however, such differences were not observed in patients who completed the survey in Chinese. The EQ-5D questionnaire appears valid for measuring quality of life in patients with PD in Singapore. However, the validity of EQ-VAS in Chinese-speaking patients with PD should be further assessed.

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists.

PubMed

Ikeda, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kawabe, Kiyokazu; Iwasaki, Yasuo

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off.

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists

PubMed Central

Ikeda, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kawabe, Kiyokazu; Iwasaki, Yasuo

2016-01-01

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off. PMID:27725534

Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non-Small Cell Lung Cancer.

PubMed

Gettinger, Scott N; Wurtz, Anna; Goldberg, Sarah B; Rimm, David; Schalper, Kurt; Kaech, Susan; Kavathas, Paula; Chiang, Anne; Lilenbaum, Rogerio; Zelterman, Daniel; Politi, Katerina; Herbst, Roy S

2018-06-01

With expanding indications for programmed death 1 (PD-1) axis inhibitors in non-small cell lung cancer (NSCLC), acquired resistance (AR) to these therapies is increasingly being encountered. We sought to characterize clinical patterns of AR to PD-1 axis inhibitors in patients with advanced NSCLC, and evaluate subsequent outcome and management strategies for such patients. Patients with NSCLC who developed AR to PD-1 axis inhibitor therapy initiated between December 2009 and February 2016 at one institution were identified and examined by clinical and radiographic features. AR was defined as progressive disease after initial response by either Response Evaluation Criteria in Solid Tumors v1.1 or immune-related response criteria. Twenty-six patients with AR to PD-1 axis inhibitor therapy were identified and evaluated. Median time to AR was 313 days; the 2-year survival rate from AR was 70% (95% confidence interval: 0.53-0.92). Twenty patients (77%) experienced AR in lymph nodes (LNs), including 11 patients with LN-only progression. Twenty-three (88%) patients had recurrence limited to one (54%) or two (35%) sites of disease. Fourteen patients (54%) continued PD-1 axis inhibitor therapy beyond progression. Three patients were re-challenged with the same PD-1 axis inhibitor after holiday from and progression off therapy, 2 again responded. Fifteen patients (58%) received local therapy to site(s) of AR, 11 continued respective PD-1 axis inhibitor after local therapy. The 2-year survival rate from AR among these 15 patients was 92% (95% confidence interval: 0.77-1). Acquired resistance to PD-1 axis inhibitors is often limited to one or two sites when local therapy and continuation of PD-1 axis inhibitor therapy can result in prolonged benefit. LN metastases appear to be particularly susceptible sites to AR. When progression of disease following response occurs after holiday from PD-1 axis inhibitor, re-challenge can again lead to tumor regression. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Association of postdischarge complications with reoperation and mortality in general surgery.

PubMed

Kazaure, Hadiza S; Roman, Sanziana A; Sosa, Julie A

2012-11-01

To describe procedure-specific types, rates, and risk factors for postdischarge (PD) complications occurring within 30 days after 21 groups of inpatient general surgery procedures. Retrospective cohort study. American College of Surgeons National Surgical Quality Improvement Program 2005 through 2010 Participant Use Data Files. A total of 551,510 adult patients who underwent one of 21 groups of general surgery procedures in the inpatient setting. Postdischarge complications, reoperation, and mortality. Of 551,510 patients (mean age, 54.6 years), 16.7% experienced a complication; 41.5% occurred PD. Of the PD complications, 75.0% occurred within 14 days PD. Proctectomy (14.5%), enteric fistula repair (12.6%), and pancreatic procedures (11.4%) had the highest PD complication rates. Breast, bariatric, and ventral hernia repair procedures had the highest proportions of complications that occurred PD (78.7%, 69.4%, and 62.0%, respectively). For all procedures, surgical site complications, infections, and thromboembolic events were the most common. Occurrence of an inpatient complication increased the likelihood of a PD complication (12.5% vs 6.2% without an inpatient complication; P < .001). Compared with patients without a PD complication, those with a PD complication had higher rates of reoperation (4.6% vs 17.9%, respectively; P < .001) and death (2.0% vs 6.9%, respectively; P < .001) within 30 days after surgery; those whose PD complication was preceded by an inpatient complication had the highest rates of reoperation (33.7%) and death (24.7%) (all P < .001). After adjustment, PD complications were associated with procedure type, American Society of Anesthesiologists class higher than 3, and steroid use. The PD complication rates vary by procedure, are commonly surgical site related, and are associated with mortality. Fastidious, procedure-specific patient triage at discharge as well as expedited patient follow-up could improve PD outcomes.

Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma.

PubMed

Maruse, Y; Kawano, S; Jinno, T; Matsubara, R; Goto, Y; Kaneko, N; Sakamoto, T; Hashiguchi, Y; Moriyama, M; Toyoshima, T; Kitamura, R; Tanaka, H; Oobu, K; Kiyoshima, T; Nakamura, S

2018-07-01

Programmed cell death ligand 1 (PD-L1) and its receptor PD-1 are immune checkpoint molecules that attenuate the immune response. Blockade of PD-L1 enhances the immune response in a variety of tumours and thus serves as an effective anti-cancer treatment. However, the biological and prognostic roles of PD-L1/PD-1 signalling in oral squamous cell carcinoma (OSCC) remain to be elucidated. The purpose of this study was to examine the correlation of PD-L1/PD-1 signalling with the prognosis of OSCC patients to assess its potential therapeutic relevance. The expression of PD-L1 and of PD-1 was determined immunohistochemically in 97 patients with OSCC and the association of this expression with clinicopathological characteristics was examined. Increased expression of PD-L1 was found in 64.9% of OSCC cases and increased expression of PD-1 was found in 61.9%. Univariate and multivariate analysis revealed that increased expression of PD-L1 and PD-1 positively correlated with cervical lymph node metastasis. The expression of CD25, an activated T-cell marker, was negatively correlated with the labelling index of PD-L1 and PD-1. Moreover, the patient group with PD-L1-positive and PD-1-positive expression showed a more unfavourable prognosis than the group with PD-L1-negative and PD-1-negative expression. These data suggest that increased PD-L1 and PD-1 expression is predictive of nodal metastasis and a poor prognosis and is possibly involved in cancer progression via attenuating the immune response. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Reliability and validity of Parkinson's disease sleep scale-Chinese version in the south west of China].

PubMed

Zhang, J H; Peng, R; Du, Y; Mou, Y; Li, N N; Cheng, L

2016-11-08

Objective: To evaluate the reliability and validity of Parkinson's disease sleep scale-Chinese version (CPDSS) through a study of a large PD population in southwest China, and to explore the prevalence and characteristics of sleep disorders in Parkinson's disease (PD) patients from southwest China. Methods: A total of 544 PD patients and 220 control subjects were enrolled in our study. Demographic data, CPDSS, ESS, PDQ39, HAMD and H-Y stage were assessed in all subjects. Statistical description, Cronbach's alpha coefficient, intra-class correlation coefficient ( ICC ), Spearman rank correlation coefficient and Mann-Whitney U test were used for statistical analyses. Result: The Cronbach's alpha coefficient for CPDSS was 0.79, ICC of the total scale was 0.94 and ICC of each item ranged from 0.73 to 0.97. The factor analysis yielded a five-factor solution, which explained 63.4% of the total variance. Total and each item scores of CPDSS in PD patients were lower than those in healthy controls. 69.3% of PD patients had sleep disorder, while prevalence in the control group was only 29.6%. Negative correlation was found between CPDSS and ESS. Daytime sleepiness was the most common factor (35.9%) leading to sleep disorders. The sleep disorders of PD patients in Southwest China were significantly related with the course of disease, the severity of disease, the quality of life, depression, cognitive level and motor symptoms. Conclusion: CPDSS has good feasibility, reliability and validity in PD population from southwest China. CPDSS is considered as an effective tool for the assessment of sleep disorder in PD patients.

Asymptomatic Effluent Protozoa Colonization in Peritoneal Dialysis Patients.

PubMed

Simões-Silva, Liliana; Correia, Inês; Barbosa, Joana; Santos-Araujo, Carla; Sousa, Maria João; Pestana, Manuel; Soares-Silva, Isabel; Sampaio-Maia, Benedita

Currently, chronic kidney disease (CKD) is a global health problem. Considering the impaired immunity of CKD patients, the relevance of infection in peritoneal dialysis (PD), and the increased prevalence of parasites in CKD patients, protozoa colonization was evaluated in PD effluent from CKD patients undergoing PD. Overnight PD effluent was obtained from 49 asymptomatic stable PD patients. Protozoa analysis was performed microscopically by searching cysts and trophozoites in direct wet mount of PD effluent and after staining smears. Protozoa were found in PD effluent of 10.2% of evaluated PD patients, namely Blastocystis hominis, in 2 patients, and Entamoeba sp., Giardia sp., and Endolimax nana in the other 3 patients, respectively. None of these patients presented clinical signs or symptoms of peritonitis at the time of protozoa screening. Our results demonstrate that PD effluent may be susceptible to asymptomatic protozoa colonization. The clinical impact of this finding should be further investigated. Copyright © 2016 International Society for Peritoneal Dialysis.

Permanent cardiac pacing in patients with end-stage renal disease undergoing dialysis.

PubMed

Wang, I-Kuan; Lin, Kuo-Hung; Lin, Shih-Yi; Lin, Cheng-Li; Chang, Chiz-Tzung; Yen, Tzung-Hai; Sung, Fung-Chang

2016-12-01

Studies investigating the risk of cardiac dysrhythmia warranting permanent pacemaker therapy for end-stage renal disease (ESRD) patients are limited. This study investigated the incidence rate of permanent cardiac pacing in dialysis patients. Using the Taiwan National Health Insurance Database, we identified 28 471 newly diagnosed ESRD patients in 2000-2010 [9700 on peritoneal dialysis (PD) and 18 771 on hemodialysis (HD)] and 113 769 randomly selected controls without kidney disease, frequency-matched by sex, age and diagnosis date. We also established propensity score-matched HD and PD cohorts with 9700 patients each. Incidence rates and hazard ratios (HRs) of implantation were evaluated by the end of 2011. Complications were also evaluated among patients with implantation. The incidence rates of permanent pacemaker implantation were 5.93- and 3.50-fold greater in HD and PD patients than in controls (1.44 and 0.85 versus 0.24 per 1000 person-years, respectively). The adjusted HRs (aHRs) of implantation were 3.26 [95% confidence interval (CI) = 2.41-4.42] and 2.36 (95% CI = 1.56-3.58) for HD and PD patients, respectively, compared with controls. The pacemaker implantation rate was 0.33 per 1000 person-years greater in the propensity score-matched HD cohort than in the PD cohort, with an aHR of 1.30 (95% CI = 0.82-2.05) for the HD cohort compared with the PD cohort. Dialysis patients are at an increased risk of dysrhythmia requiring pacemaker implantation compared with the general population. The risks are not significantly different between HD and PD patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A study of the clinical and biochemical profile of peritoneal dialysis fluid low in glucose degradation products.

PubMed

Lai, Kar Neng; Lam, Man Fai; Leung, Joseph C K; Chan, Loretta Y; Lam, Christopher W K; Chan, Iris H S; Chan, Hoi Wong; Li, Chun Sang; Wong, Sunny S H; Ho, Yiu Wing; Cheuk, Au; Tong, Matthew K L; Tang, Sydney C W

2012-01-01

Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum.

A Study of the Clinical and Biochemical Profile of Peritoneal Dialysis Fluid Low in Glucose Degradation Products

PubMed Central

Lai, Kar Neng; Lam, Man Fai; Leung, Joseph C.K.; Chan, Loretta Y.; Lam, Christopher W.K.; Chan, Iris H.S.; Chan, Hoi Wong; Li, Chun Sang; Wong, Sunny S.H.; Ho, Yiu Wing; Cheuk, Au; Tong, Matthew K.L.; Tang, Sydney C.W.

2012-01-01

♦ Objective: Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. ♦ Methods: We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. ♦ Results: Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. ♦ Conclusions: It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum. PMID:22045098

Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells

PubMed Central

Liao, Yunfei; Chen, Lulu; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

2017-01-01

Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed on tumor cells that suppresses the T cell-mediated immune response. Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown promising results in some types of cancers. However, the functional and therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study, we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue microarray of patient tumors. Tissue microarray immunohistochemistry analysis showed that the overall and five-year survival rates of patients with high levels of PD-L1 expression were significantly shorter than patients with low levels. High levels of PD-L1 expression were also associated with metastasis in osteosarcoma patients. Furthermore, we applied the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to target PD-L1 gene at the DNA level in osteosarcoma cell lines. We found that the expression of PD-L1 could be efficiently disrupted by CRISPR/Cas9 system and PD-L1 knockdown increased drug sensitivities for doxorubicin and paclitaxel. These results suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of osteosarcoma. PMID:28415820

Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells.

PubMed

Liao, Yunfei; Chen, Lulu; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

2017-05-02

Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed on tumor cells that suppresses the T cell-mediated immune response. Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown promising results in some types of cancers. However, the functional and therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study, we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue microarray of patient tumors. Tissue microarray immunohistochemistry analysis showed that the overall and five-year survival rates of patients with high levels of PD-L1 expression were significantly shorter than patients with low levels. High levels of PD-L1 expression were also associated with metastasis in osteosarcoma patients. Furthermore, we applied the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to target PD-L1 gene at the DNA level in osteosarcoma cell lines. We found that the expression of PD-L1 could be efficiently disrupted by CRISPR/Cas9 system and PD-L1 knockdown increased drug sensitivities for doxorubicin and paclitaxel. These results suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of osteosarcoma.

Driving safety in Parkinson's disease.

PubMed

Zesiewicz, T A; Cimino, C R; Malek, A R; Gardner, N; Leaverton, P L; Dunne, P B; Hauser, R A

2002-12-10

In this study, 39 patients with PD and 25 control subjects without neurologic disease completed testing in a driving simulator. PD patients had more total collisions on the driving simulator than control subjects (t = -3.7, p < 0.01). In PD patients, collisions were associated with Hoehn and Yahr stage (chi(2) = 12.4, p = 0.006) and correlated with Unified Parkinson's Disease Rating Scale score (r = 0.5, p < 0.01).

The impact of the peritoneal glucose load index on hydration status and inflammation in peritoneal dialysis patients.

PubMed

Hassan, Kamal; Hassan, Fadi; Edgem, Rabia; Moshe, Smadar; Hassan, Shadi

2015-02-01

To evaluate the impact of the peritoneal glucose load (PGL) on hydration status and inflammation in peritoneal dialysis (PD) patients. This cross-sectional study evaluated stable PD patients using a novel PGL index (PGLI), which was calculated as the net glucose content (g) in the PD solutions administered in the daily PD prescription divided by the dry body weight (kg) assessed by whole-body bioimpedance spectroscopy. The relationship between PGLI and glycosylated haemoglobin (HbA1c), fluid overload (FO), and inflammatory markers was investigated. A total of 43 stable PD patients participated in the study. Significant positive correlations were found between PGLI and HbA1c, FO, plasma high sensitivity C-reactive protein (hsCRP), and plasma interleukin-6 (IL-6) levels. HbA1c, FO, plasma hsCRP and plasma IL-6 levels were significantly higher in patients with PGLI >3 g/kg/day compared with those with PGLI ≤3 g/kg/day. PGLI values >3 g/kg/day may be associated with poor glycaemic control, over hydration and augmented inflammation. PGLI might be a useful tool for the quantitative assessment of the PGL and could be applied when managing PD patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Risk of hematologic toxicities with programmed cell death-1 inhibitors in cancer patients: a meta-analysis of current studies.

PubMed

Sui, Jiang-Dong; Wang, Ying; Wan, Yue; Wu, Yong-Zhong

2018-01-01

Programmed cell death-1 (PD-1) inhibitor-related hematologic toxicities are a category of rare but clinically serious and potentially life-threatening adverse events; however, little is known about their risks across different treatment regimens and tumor types. The objective of this study was to compare the incidences of PD-1 inhibitor-related hematologic toxicities among different therapeutic regimens and tumor types. Twenty-six original articles on PD-1 inhibitor trials were identified based on a PubMed search completed on September 26, 2017. The incidences of hematologic toxicities were collected. A total of 26 studies containing 5,088 patients were included in the meta-analysis. PD-1 inhibitor monotherapy was associated with an increased risk of all-grade anemia in cancer patients (5%, 95% CI 4%-6%), particularly in patients with renal cell carcinoma (RCC) (8%, 95% CI 6%-12%), compared with all-grade thrombocytopenia (2%, 95% CI 1%-5%), leukopenia (2%, 95% CI 1%-3%), and neutropenia (1%, 95% CI 0-1%). However, low incidences of high-grade hematologic toxicities were observed in cancer patients treated with PD-1 inhibitor monotherapy. The use of PD-1 inhibitors in combination with ipilimumab, peptide vaccines, or chemotherapy had significantly higher risks than PD-1 inhibitor monotherapy for all-grade anemia (13%, 95% CI 5%-31%), thrombocytopenia (6%, 95% CI 2%-18%), leukopenia (5%, 95% CI 1%-35%), neutropenia (4%, 95% CI 1%-26%), and only high-grade thrombocytopenia (4%, 95% CI 1%-15%). In addition, all-grade and high-grade hematologic toxicities in chemotherapy and everolimus treatment arms were more frequent than in PD-1 inhibitor monotherapy arms. The risks of PD-1 inhibitor-related hematologic toxicities were higher in RCC than in other cancers, and during combination therapy. These results may contribute toward enhancing awareness among clinicians about frequent clinical monitoring when managing PD-1 inhibitors.

Tissue advanced glycation end products (AGEs), measured by skin autofluorescence, predict mortality in peritoneal dialysis.

PubMed

Siriopol, Dimitrie; Hogas, Simona; Veisa, Gabriel; Mititiuc, Irina; Volovat, Carmen; Apetrii, Mugurel; Onofriescu, Mihai; Busila, Irina; Oleniuc, Mihaela; Covic, Adrian

2015-03-01

The relation between tissue AGEs and mortality in end-stage renal disease (ESRD) is documented, but only in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGEs levels in patients receiving either HD or peritoneal dialysis (PD) and to study the effect of these products on all-cause, cardiovascular or sepsis-related mortality. Tissue AGEs were noninvasively assessed in 304 dialysis patients (202 on chronic HD and 102 on continuous ambulatory PD) by measuring skin autofluorescence using a validated Autofluorescence Reader (AGE Reader, DiagnOptics b.v., Groningen, The Netherlands). There was no difference in regard to AGEs levels between the HD (3.6 ± 0.8 AU)- and PD (3.5 ± 0.7 AU, p = 0.2)-treated patients. Diabetic patients had higher AGEs values in the HD group (3.97 ± 0.81 vs. 3.52 ± 0.77, p = 0.002), but not in the PD group (3.68 ± 0.6 vs. 3.45 ± 0.70, p = 0.26). In PD patients, increasing AGEs levels were associated with an elevated risk of all-cause mortality (a 2.09-fold increase for each increment of 1 AU in AGEs values) and sepsis (a 3.44-fold increase for each increment of 1 AU in AGEs values)-related mortality. Performing a similar analysis in diabetic patients, AGEs was associated only with sepsis-related mortality (a 3.08-fold increase for each increment of 1 AU in AGEs values). This is the first study that demonstrates a relationship between tissue AGEs levels and sepsis-related mortality in PD-treated or diabetic ESRD patients. Future studies are necessary to evaluate the non-cardiovascular effects of tissue AGEs in ESRD patients.

Effects of Health Qigong Exercises on Relieving Symptoms of Parkinson's Disease.

PubMed

Liu, Xiao Lei; Chen, Shihui; Wang, Yongtai

2016-01-01

The purpose of this study was to investigate the effects of Health Qigong on the treatment and releasing symptoms of Parkinson's disease (PD). Fifty-four moderate PD patients ( N = 54) were randomly divided into experimental and control groups. Twenty-eight PD patients were placed in the experimental group in which the prescribed medication plus Health Qigong exercise will be used as intervention. The other 26 PD patients as the control group were treated only with regular medication. Ten-week intervention had been conducted for the study, and participants completed the scheduled exercises 5 times per week for 60 minutes each time (10 minutes for warm-up, 40 minutes for the exercise, and 10 minutes for cooldown). Data which included the muscle hardness, one-legged blind balance, physical coordination, and stability was collected before, during, and after the intervention. Comparisons were made between the experimental and control groups through the Repeated Measures ANOVA. The results showed that PD patients demonstrate a significant improvement in muscle hardness, the timed "up and go," balance, and hand-eye coordination (the turn-over-jars test). There were no significant differences between the two groups in gender, age, and course of differences ( P < 0.05). The study concluded that Health Qigong exercises could reduce the symptoms of Parkinson's disease and improve the body functions of PD patients in both the mild and moderate stages. It can be added as an effective treatment of rehabilitation therapy for PD.

Effects of Health Qigong Exercises on Relieving Symptoms of Parkinson's Disease

PubMed Central

Liu, Xiao Lei; Wang, Yongtai

2016-01-01

The purpose of this study was to investigate the effects of Health Qigong on the treatment and releasing symptoms of Parkinson's disease (PD). Fifty-four moderate PD patients (N = 54) were randomly divided into experimental and control groups. Twenty-eight PD patients were placed in the experimental group in which the prescribed medication plus Health Qigong exercise will be used as intervention. The other 26 PD patients as the control group were treated only with regular medication. Ten-week intervention had been conducted for the study, and participants completed the scheduled exercises 5 times per week for 60 minutes each time (10 minutes for warm-up, 40 minutes for the exercise, and 10 minutes for cooldown). Data which included the muscle hardness, one-legged blind balance, physical coordination, and stability was collected before, during, and after the intervention. Comparisons were made between the experimental and control groups through the Repeated Measures ANOVA. The results showed that PD patients demonstrate a significant improvement in muscle hardness, the timed “up and go,” balance, and hand-eye coordination (the turn-over-jars test). There were no significant differences between the two groups in gender, age, and course of differences (P < 0.05). The study concluded that Health Qigong exercises could reduce the symptoms of Parkinson's disease and improve the body functions of PD patients in both the mild and moderate stages. It can be added as an effective treatment of rehabilitation therapy for PD. PMID:27891159

[Inferior frontal region hypoperfusion in Parkinson disease with dementia].

PubMed

Ochudło, Stanisław; Opala, Grzegorz; Jasińska-Myga, Barbara; Siuda, Joanna; Nowak, Stanisław

2003-01-01

Dementia is more frequent in patients suffering from Parkinson's disease (PD) then in general population. The mechanism for mental deterioration in PD remains controversial. The aim of our study was comparison of the regional cerebral perfusion quantified by single photon emission computed tomography in patients suffering from idiopathic Parkinson's disease with and without dementia. We examined 49 PD patients: 22 PD patients with dementia and 27 PD patients without dementia. Dementia was recognized according to ICD-10 and DSM-IV criteria. Cognitive functions were executed by means of the Mini Mental State Examination (MMSE) and neuropsychological assessment. The Unified Parkinson's Disease Rating Scale (UPDRS) and Modified Hoehn & Yahr Scale was used to quantify the severity of PD. SPECT was performed with Siemens Diacam single--head rotating gamma camera after intravenous application of technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO). The perfusion values were expressed as cortical or basal ganglia regions of interest (ROIs)/cerebellum activity ratios. In both examined group of patients the lowest uptake was in basal ganglia region, while the highest uptake was in occipital region. In the subgroup of PD patients with dementia significant hypoperfusion affecting the inferior frontal cortices was observed. In Parkinson's disease with dementia hypoperfusion in inferior frontal region can be found.

Hyposalivation and xerostomia among Parkinson's disease patients and its impact on quality of life.

PubMed

Barbe, A G; Heinzler, A; Derman, Shm; Hellmich, M; Timmermann, L; Noack, M J

2017-05-01

Parkinson's disease (PD) adversely affects oral health (OH). However, the informative value of xerostomia compared to objective parameters and its impact on quality of life (QoL) are still unclear. This study aimed to explore whether xerostomia correlates with hyposalivation and to define its impact on OH-related QoL. Whole stimulated saliva (WSS) was collected from 30 patients with PD and 30 matched healthy controls. Objective parameters (community periodontal index of treatment needs, plaque/gingivitis index, mucosa situation and cheilitis angularis) and questionnaires (German Oral Health Impact Profile [OHIPG]-14, visual analogue scale [VAS], xerostomia [yes/no] and the Unified Parkinson's Disease Rating Scale-II) were assessed. Eighty-seven per cent of patients with PD showed hyposalivation vs 50% of controls (P = 0.001); 50% of patients with PD reported xerostomia, and none of controls (P < 0.001). The OHIPG-14 was impaired in patients with PD compared to controls (P < 0.001), PD patients with xerostomia reported mean VAS values of 4.1 (s.d.: 2.2). WSS did not correlate with VAS values. Half of the patients with PD reported xerostomia and underestimated their xerostomic status, with higher probability than healthy controls. WSS did not reflect the grade of xerostomia. Patients with PD suffered from impaired OH-related QoL. Dental teams should not overlook these oral health risks. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increased Risk of Dementia in Patients With Chronic Obstructive Pulmonary Disease.

PubMed

Liao, Kuang-Ming; Ho, Chung-Han; Ko, Shian-Chin; Li, Chung-Yi

2015-06-01

Neurodegenerative disease in patients with chronic obstructive pulmonary disease (COPD) was observed. We aim to clarify the risk of dementia in patients with COPD. The study used claims data from Taiwan's National Health Insurance Research Database. Subjects were those who received a discharge diagnosis of COPD between January 1, 2002 and December 31, 2011. Only the first hospitalization was enrolled, and the index date was the first day of admission. Patients younger than 40 years or those with a history of Alzheimer disease (AD) or Parkinson disease (PD) before the index date were excluded. The patients with COPD were then followed until receiving a diagnosis of AD or PD, death, or the end of the study. Control subjects were selected from hospitalized patients without a history of COPD, AD, or PD and were matched according to age (±3 years), gender, and the year of admission at a 2:1 ratio. The comorbidities were measured from 1 year before the index date based on the ICD-9-CM codes. The study included 8640 patients with COPD and a mean age of 68.76 (±10.74) years. The adjusted hazard ratio of developing dementia (AD or PD) was 1.74 (95% confidence interval = 1.55-1.96) in patients with COPD compared with patients without COPD after adjusting for age, gender, and comorbidities. This nationwide cohort study demonstrates that the risk of dementia, including AD and PD, is significantly increased in patients with COPD compared with individuals in the general population.

[Personality disorders in adolescent patients with anorexia and bulimia nervosa].

PubMed

Bottin, Julia; Salbach-Andrae, Harriet; Schneider, Nora; Pfeiffer, Ernst; Lenz, Klaus; Lehmkuhl, Ulrike

2010-09-01

The present study aimed to ascertain the occurrence of personality disorders (PD) in adolescent patients with anorexia (AN) and bulimia nervosa (BN) by means of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). 99 female adolescent patients (57 AN - restrictive type, 17 AN - binge-purging type, 25 BN; M(age) = 16.3 +/- 1.6) were consecutively assessed by means of SCID-II. Furthermore, the influence of age, axis-I-comorbidities, and type of treatment according to PD were examined. 30.3% of the patients met the criteria for PD according to SCID-II. AN patients of the binge-purging type showed higher prevalences of PD and higher dimensional scores than the other eating disorder groups. Moreover, our findings indicate that age and axis-I-comorbidities are associated with the development of PD. Significant differences in the occurrence of PD in the three eating disorder groups were found. Patients of the AN binge-purging type are more often affected than restricting AN or BN patients are. This, and also the influence of age and axis-I-comorbidities, should be taken into account in the treatment of patients with eating disorders.

Clinical Significance of PD-L1+ Exosomes in Plasma of Head and Neck Cancer Patients.

PubMed

Theodoraki, Marie-Nicole; Yerneni, Saigopalakrishna S; Hoffmann, Thomas K; Gooding, William E; Whiteside, Theresa L

2018-02-15

Purpose: The microenvironment of head and neck squamous cell carcinomas (HNSCC) is highly immunosuppressive. HNSCCs expressing elevated levels of PD-L1 have especially poor outcome. Exosomes that carry PD-L1 and suppress T-cell functions have been isolated from plasma of patients with HNSCC. The potential contributions of PD-L1 + exosomes to immune suppression and disease activity are evaluated. Experimental Design: Exosomes isolated from plasma of 40 HNSCC patients by size exclusion chromatography were captured on beads using anti-CD63 Abs, stained for PD-1 and PD-L1 and analyzed by flow cytometry. The percentages and mean fluorescence intensities (MFI) of PD-L1 + and PD-1 + exosome/bead complexes were correlated with the patients' clinicopathologic data. PD-L1 high or PD-L1 low exosomes were incubated with activated CD69 + human CD8 + T cells ± PD-1 inhibitor. Changes in CD69 expression levels on T cells were measured. Patients' plasma was tested for soluble PD-L1 (sPD-L1) by ELISA. Results: Levels of PD-L1 carried by exosomes correlated with patients' disease activity, the UICC stage and the lymph node status ( P = 0.0008-0.013). In contrast, plasma levels of sPD-L1 or exosome PD-1 levels did not correlate with any clinicopathologic parameters. CD69 expression levels were inhibited ( P < 0.03) by coincubation with PD-L1 high but not by PD-L1 low exosomes. Blocking of PD-L1 + exosome signaling to PD-1 + T cells attenuated immune suppression. Conclusions: PD-L1 levels on exosomes, but not levels of sPD-L1, associated with disease progression in HNSCC patients. Circulating PD-L1 + exosomes emerge as useful metrics of disease and immune activity in HNSCC patients. Circulating PD-L1 high exosomes in HNC patients' plasma but not soluble PD-L1 levels associate with disease progression. Clin Cancer Res; 24(4); 896-905. ©2017 AACR . ©2017 American Association for Cancer Research.

Asymmetric pain processing in Parkinson's disease.

PubMed

Granovsky, Y; Schlesinger, I; Fadel, S; Erikh, I; Sprecher, E; Yarnitsky, D

2013-10-01

Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Pathophysiology of Small-Fiber Sensory System in Parkinson's Disease

PubMed Central

Lin, Chin-Hsien; Chao, Chi-Chao; Wu, Shao-Wei; Hsieh, Paul-Chen; Feng, Fang-Ping; Lin, Yea-Huey; Chen, Ya-Mei; Wu, Ruey-Meei; Hsieh, Sung-Tsang

2016-01-01

Abstract Sensory symptoms are frequent nonmotor complaints in patients with Parkinson's disease (PD). However, few investigations integrally explored the physiology and pathology of the thermonociceptive pathway in PD. We aim to investigate the involvement of the thermonociceptive pathway in PD. Twenty-eight PD patients (16 men, with a mean age and standard deviation of 65.6 ± 10.7 years) free of neuropathic symptoms and systemic disorders were recruited for the study and compared to 23 age- and gender-matched control subjects (12 men, with a mean age and standard deviation of 65.1 ± 9.9 years). We performed skin biopsy, contact heat-evoked potential (CHEP), and quantitative sensory tests (QST) to study the involvement of the thermonociceptive pathway in PD. The duration of PD was 7.1 ± 3.2 (range 2–17 years) years and the UPDRS part III score was 25.6 ± 9.7 (range 10–48) during the off period. Compared to control subjects, PD patients had reduced intra-epidermal nerve fiber (IENF) density (2.48 ± 1.65 vs 6.36 ± 3.19 fibers/mm, P < 0.001) and CHEP amplitude (18.02 ± 10.23 vs 33.28 ± 10.48 μV, P < 0.001). Twenty-three patients (82.1%) had abnormal IENF densities and 18 (64.3%) had abnormal CHEP. Nine patients (32.1%) had abnormal thermal thresholds in the feet. In total 27 patients (96.4%) had at least 1 abnormality in IENF, CHEP, or thermal thresholds of the foot, indicating dysfunctions in the small-fiber nerve system. In control subjects, CHEP amplitude linearly correlated with IENF density (P < 0.001). In contrast, this relationship disappeared in PD (P = 0.312) and CHEP amplitude was negatively correlated with motor severity of PD independent of age, gender, and anti-PD medication dose (P = 0.036), suggesting the influences of central components on thermonociceptive systems in addition to peripheral small-fiber nerves in PD. The present study suggested impairment of small-fiber sensory system at both peripheral and central levels is an intrinsic feature of PD, and skin biopsy, CHEP, and QST provided an integral approach for assessing such dysfunctions. PMID:26962835

A mobile cloud-based Parkinson's disease assessment system for home-based monitoring.

PubMed

Pan, Di; Dhall, Rohit; Lieberman, Abraham; Petitti, Diana B

2015-03-26

Parkinson's disease (PD) is the most prevalent movement disorder of the central nervous system, and affects more than 6.3 million people in the world. The characteristic motor features include tremor, bradykinesia, rigidity, and impaired postural stability. Current therapy based on augmentation or replacement of dopamine is designed to improve patients' motor performance but often leads to levodopa-induced adverse effects, such as dyskinesia and motor fluctuation. Clinicians must regularly monitor patients in order to identify these effects and other declines in motor function as soon as possible. Current clinical assessment for Parkinson's is subjective and mostly conducted by brief observations made during patient visits. Changes in patients' motor function between visits are hard to track and clinicians are not able to make the most informed decisions about the course of therapy without frequent visits. Frequent clinic visits increase the physical and economic burden on patients and their families. In this project, we sought to design, develop, and evaluate a prototype mobile cloud-based mHealth app, "PD Dr", which collects quantitative and objective information about PD and would enable home-based assessment and monitoring of major PD symptoms. We designed and developed a mobile app on the Android platform to collect PD-related motion data using the smartphone 3D accelerometer and to send the data to a cloud service for storage, data processing, and PD symptoms severity estimation. To evaluate this system, data from the system were collected from 40 patients with PD and compared with experts' rating on standardized rating scales. The evaluation showed that PD Dr could effectively capture important motion features that differentiate PD severity and identify critical symptoms. For hand resting tremor detection, the sensitivity was .77 and accuracy was .82. For gait difficulty detection, the sensitivity was .89 and accuracy was .81. In PD severity estimation, the captured motion features also demonstrated strong correlation with PD severity stage, hand resting tremor severity, and gait difficulty. The system is simple to use, user friendly, and economically affordable. The key contribution of this study was building a mobile PD assessment and monitoring system to extend current PD assessment based in the clinic setting to the home-based environment. The results of this study proved feasibility and a promising future for utilizing mobile technology in PD management.

Analysis of oropharyngeal dysphagia through fibroendoscopy evaluation of swallowing in patients with Parkinson's disease.

PubMed

Correa-Flores, Melissa; Arch-Tirado, Emilio; Villeda-Miranda, Alicia; Rocha-Cacho, Karina Elizabeth; Verduzco-Mendoza, Antonio; Hernández-López, Xochiquetzal

2012-01-01

Parkinson's disease (PD) has a high incidence in Mexico and is estimated at approximately 500,000 patients. One of the main clinical manifestations of PD is dysphagia, which is the difficult passage of food from the mouth to the stomach. The aim of this study was to assess oropharyngeal dysphagia through fibroendoscopy evaluation of swallowing in patients with PD. We conducted a census sample of patients with PD: 17 males and 10 females, aged >49 years. Clinical history, physical examination and neurological evaluation of swallowing fibroendoscopy were carried out. Of the symptomatic patients, 16 patients (59.25%) reported dysphagia. Fibroendoscopic evaluation demonstrated swallowing disorders in 25 patients (92.59%). The main findings were poor bolus control in 19 patients (70.37%), deficits in bolus propulsion in 25 patients (92.59%), impaired swallowing in 14 patients (51.85%), fractional swallowing in 11 patients (40.74%), reduced epiglottic tilting in 11 patients (48.14%), food residue in vallecula in 24 patients (88.88%) and piriform sinus in 19 patients (70.37%). There was no correlation between duration of PD and degree of involvement of oropharyngeal dysphagia. Oropharyngeal dysphagia in patients with PD is a common symptom and can range from the oral cavity to the upper esophageal sphincter. Early onset of severe dysphagia is exceptional in this disease and should alert the clinician to the diagnostic possibility of parkinsonism.

Cardiovascular Autonomic Dysfunction in Patients with Drug-Induced Parkinsonism

PubMed Central

Ryu, Dong-Woo; Oh, Ju-Hee; Lee, Yang-Hyun; Park, Sung-Jin; Jeon, Kipyung; Lee, Jong-Yun; Ho, Seong Hee; So, Jungmin; Im, Jin Hee; Lee, Kwang-Soo

2017-01-01

Background and Purpose Recent studies have shown that several nonmotor symptoms differ between Parkinson's disease (PD) and drug-induced parkinsonism (DIP). However, there have been no reports on cardiovascular autonomic function in DIP, and so this study investigated whether cardiovascular autonomic function differs between PD and DIP patients. Methods This study consecutively enrolled 20 DIP patients, 99 drug-naïve PD patients, and 25 age-matched healthy controls who underwent head-up tilt-table testing and 24-h ambulatory blood pressure monitoring. Results Orthostatic hypotension was more frequent in patients with PD or DIP than in healthy controls. In DIP, orthostatic hypotension was associated with the underlying psychiatric diseases and neuroleptics use, whereas prokinetics were not related to orthostatic hypotension. The supine blood pressure, nighttime blood pressure, and nocturnal blood pressure dipping did not differ significantly between the DIP and control groups. Supine hypertension and nocturnal hypertension were more frequent in PD patients than in controls. Conclusions The included DIP patients frequently exhibited orthostatic hypotension that was associated with the underlying diseases as well as the nature of and exposure time to the offending drugs. Clinicians should individualize the manifestations of DIP according to underlying diseases as well as the action mechanism of and exposure time to each offending drug. PMID:27730767

Effects of Rotigotine on REM Sleep Behavior Disorder in Parkinson Disease

PubMed Central

Wang, Yan; Yang, Yuechang; Wu, Huijuan; Lan, Danmei; Chen, Ying; Zhao, Zhongxin

2016-01-01

Study Objectives: REM sleep behavior disorder (RBD) is a common manifestation of Parkinson disease (PD). In this study, we assessed the effects of rotigotine transdermal patch on RBD features in patients with PD. Methods: In this prospective open-label study, eleven PD patients with untreated RBD were administered rotigotine patches for up to seven months to ameliorate their parkinsonism. The severities of their RBD symptoms before and after rotigotine therapy were evaluated through patient and bed partner interviews, a validated evaluation scale (REM sleep behavior disorder questionnaire-Hong Kong, RBDQ-HK), and blinded assessments based on video-polysomnographic (VPSG) measure. Results: Rotigotine improved parkinsonism and subjective sleep quality in PD patients with RBD. The RBDQ-HK total score, especially the Factor 2 score, was decreased, which demonstrated that the subjective severity of RBD symptoms was improved after rotigotine treatment, especially the frequency and severity of abnormal RBD-related motor behaviors. The VPSG analyses showed that the total sleep time (TST) and stage 1% were increased and that the PLMS index was decreased. However, no differences in the RBD-related sleep measures were observed. Conclusions: The improved RBD symptoms and VPSG measures of PD patients in this study (TST, stage 1%, and PLMS index) suggest that, in PD, rotigotine may partially improve RBD-related symptoms. Rotigotine should be considered to be an optional drug for the treatment of RBD symptoms in PD. Citation: Wang Y, Yang Y, Wu H, Lan D, Chen Y, Zhao Z. Effects of rotigotine on REM sleep behavior disorder in Parkinson disease. J Clin Sleep Med 2016;12(10):1403–1409. PMID:27568909

Association of rapid eye movement sleep behavior disorder with sleep-disordered breathing in Parkinson's disease.

PubMed

Zhang, Lin-Yuan; Liu, Wen-Yan; Kang, Wen-Yan; Yang, Qiong; Wang, Xiao-Ying; Ding, Jian-Qing; Chen, Sheng-Di; Liu, Jun

2016-04-01

Rapid eye movement (REM) sleep behavior disorder (RBD) and sleep-disordered breathing (SDB) are two major sleep disturbances observed in patients with Parkinson's disease (PD). However, prior studies exploring the clinical correlations between RBD and SDB in PD have been limited. We aimed to investigate the relationship between RBD and SDB in PD using a case-control study. A total of 46 PD patients with Hoehn-Yahr stages ranging from 1 to 3 participated in the present study. Participants underwent polysomnography to diagnose the presence of RBD and SDB, and were classified into groups, accordingly. SDB was defined as an apnea-hypopnea index greater than 5. Comparison of clinical and sleep-respiratory parameters was performed among them. SDB was more frequent in the RBD group than in the non-RBD group (51.4% vs 9.1%, p = 0.016). PD patients with RBD had significantly reduced mean SaO2 and more severe sleep apnea-related parameters during total sleep and non-REM sleep in comparison with non-RBD PD patients. However, there were no differences on the REM-related apnea/hypopnea variables between participants with and without RBD (p > 0.05). Both the frequency of RBD and RBD screening questionnaire (RBDSQ) scores were higher in the participants with SDB than in the participants without SDB (p <0.05). Furthermore, a significant negative correlation was found between RBDSQ and mean SaO2 in all participants. In PD patients, SDB is more frequent and more severe in patients with RBD than in patients without, and RBD increases the risk of hypoxemia during sleep. Copyright © 2016 Elsevier B.V. All rights reserved.

Reduction of gastrointestinal symptoms in Parkinson's disease after a switch from oral therapy to rotigotine transdermal patch: a non-interventional prospective multicenter trial.

PubMed

Woitalla, Dirk; Kassubek, Jan; Timmermann, Lars; Lauterbach, Thomas; Berkels, Reinhard; Grieger, Frank; Müller, Thomas

2015-03-01

Gastrointestinal (GI) symptoms are common among patients with Parkinson's disease (PD), due to both the disease itself and anti-PD drugs. We hypothesized that transdermal drug administration may result in fewer GI problems. This prospective observational study (ClinicalTrials.gov: NCT01159691) investigated effect of switching to rotigotine transdermal patch from oral anti-PD medications in patients with PD and existing GI symptoms. Patients were enrolled if their physician was planning to switch them to rotigotine because of GI symptoms experienced while receiving oral anti-PD medications. Effectiveness assessments included a visual analog scale (VAS) measuring intensity of GI symptoms from 0 (no disorder) to 100 mm (extremely severe disorder), a questionnaire on the frequency and intensity of six individual GI complaints (heartburn, bloating, nausea, vomiting, abdominal pain, diarrhea), each rated 0-12 for a sum score of 0-72, and patient satisfaction regarding GI symptoms over approximately 6 weeks after switching. Of 75 patients who received rotigotine, 58 had follow-up data available for final analysis. Intensity of GI complaints improved numerically on both the VAS (47.5 ± 24.4 mm [n = 65] at baseline, 19.7 ± 23.3 mm [n = 58] after around 6 weeks) and the sum score of GI complaints (11.2 ± 9.0 at baseline, 2.1 ± 4.4 [n = 58] after around 6 weeks). Fifty of 58 patients were "satisfied" or "very satisfied" regarding GI symptoms over around 6 weeks following switch to the patch. This study suggests that a switch from oral anti-PD medications to rotigotine transdermal patch may improve existing GI symptoms among patients with PD. Additional controlled studies are needed to confirm this finding. Copyright © 2014 Elsevier Ltd. All rights reserved.

Peritoneal dialysis peritonitis by anaerobic pathogens: a retrospective case series

PubMed Central

2013-01-01

Background Bacterial infections account for most peritoneal dialysis (PD)-associated peritonitis episodes. However, anaerobic PD peritonitis is extremely rare and intuitively associated with intra-abdominal lesions. In this study, we examined the clinical characteristics of PD patients who developed anaerobic peritonitis. Methods We retrospectively identified all anaerobic PD peritonitis episodes from a prospectively collected PD registry at a single center between 1990 and 2010. Only patients receiving more than 3 months of PD were enrolled. We analyzed clinical features as well as outcomes of anaerobic PD peritonitis patients. Results Among 6 patients, 10 episodes of PD-associated peritonitis were caused by anaerobic pathogens (1.59% of all peritonitis episodes during study the period), in which the cultures from 5 episodes had mixed growth. Bacteroides fragilis was the most common species identified (4 isolates). Only 3 episodes were associated with gastrointestinal lesions, and 4 episodes were related to a break in sterility during exchange procedures. All anaerobic pathogens were susceptible to clindamycin and metronidazole, but penicillin resistance was noted in 4 isolates. Ampicillin/sulbactam resistance was found in 2 isolates. In 5 episodes, a primary response was achieved using the first-generation cephalosporin and ceftazidime or aminoglycoside. In 3 episodes, the first-generation cephalosporin was replaced with aminoglycosides. Tenckhoff catheter removal was necessary in 2 episodes. Only one episode ended with mortality (due to a perforated bowel). Conclusion Anaerobic PD-associated peritonitis might be predominantly caused by contamination, rather than intra-abdominal events. Half of anaerobic PD-associated peritonitis episodes had polymicrobial growth. The overall outcome of anaerobic peritonitis is fair, with a high catheter survival rate. PMID:23705895

Premorbid dietetic habits and risk for Parkinson's disease.

PubMed

Ayuso-Peralta, L; Jiménez-Jiménez, F J; Cabrera-Valdivia, F; Molina, J; Javier, M R; Almazán; De Pedro-Cuesta, J; Tabernero, C; Giménez-Roldán, S

1997-01-01

To evaluate the possible role of antioxidant (vitamins A, E, C, beta-carotene, zinc, selenium) or pro-oxidant (iron, copper, manganese) factors present in the diet, in the risk for Parkinson's disease (PD), we conducted a dietetic study (pre- and postmarriage) which included 91 foodstuffs. We interviewed separately 119 PD patients (64 males, 55 females, age 65.3 +/- 8.5 years, age at marriage 27.8 +/- 5.9 years) and their spouses (age 65.0 +/- 9.2 years, age at marriage 27.2 +/- 5.9 years) as the control group (C). Premarriage consumption for each foodstuff was classified into: (1) rarely of annually, (2) monthly, or (3) weekly; and postmarriage consumption (which included the period between age at marruage and age 40 years; only concordant answers were considered to be valid) into: (1) PD > Control, (2) Control > PD, and (3) PD = Control. The premarriage interview showed a trend towards a lower consumption of peas in PD patients as compared to controls. The postmarriage interview in PD patients showed a higher tendency for the consumption of rice, bluefish, liver paté and eggs, and a less consumption of tea than controls. We were unable to find any consistent trend towards a lower consumption of vitamins E and C during adulthood in PD patients, but they seemed to have eaten selenium-rich foodstuffs more frequently than controls. These results differ from those obtained by previous studies, and question the possible role of premorbid dietary habits on the risk for PD.

OLFACTORY DYSFUNCTION IN PARKINSON’S DISEASE: POSITIVE EFFECT OF CIGARETTE SMOKING

PubMed Central

Sharer, James D.; Leon-Sarmiento, Fidias E.; Morley, James F.; Weintraub, Daniel; Doty, Richard L.

2014-01-01

Background There is compelling evidence from over 60 epidemiological studies that smoking significantly reduces the risk of Parkinson’s disease (PD). In general, those who currently smoke cigarettes, as well as those with a past history of such smoking, have a reduced risk of PD compared to those who have never smoked. Recently it has been suggested that a cardinal non-motor sensory symptom of PD, olfactory dysfunction, may be less severe in PD patients who smoke than in PD patients who do not, in contrast to the negative effect of smoking on olfaction described in the general population. Methods We evaluated University of Pennsylvania Smell Identification Test (UPSIT) scores from 323 Parkinson’s patients and 323 controls closely matched individually on age, sex, and smoking history (never, past, current). Results The patients exhibited much lower UPSIT scores than did the controls (P<0.0001). The relative decline in dysfunction of the current PD smokers was less than that of the never- and past-PD smokers (respective Ps=0.0005 & 0.0019). The female PD patients outperformed their male counterparts by a larger margin than did the female controls (3.66 vs. 1.07 UPSIT points; respective Ps < 0.0001 & 0.06). Age-related declines in UPSIT scores were generally present (P < 0.0001). No association between the olfactory measure and smoking dose, as indexed by pack years, was evident. Conclusions PD patients who currently smoke do not exhibit the smoking-related decline in olfaction observed in non-PD control subjects who currently smoke. The physiologic basis of this phenomenon is yet to be defined. PMID:25545729

Economic impact of disease progression in follicular non-Hodgkin lymphoma

PubMed Central

Beveridge, Roy; Satram-Hoang, Sacha; Sail, Kavita; Darragh, Joseph; Chen, Clara; Forsyth, Michael; Reyes, Carolina

2011-01-01

Using a retrospective claims database, we estimated the economic costs of progression among patients with follicular non-Hodgkin lymphoma (f-NHL) treated in an outpatient community-based setting. Patients with f-NHL who received care between 1 July 2006 and 31 December 2009 were categorized into two cohorts based on whether they experienced progressive disease (PD) or not. Costs per patient per month (PPPM) were compared between patients with PD versus non-PD. Follow-up time was censored at the last entry for disease status or 6 months after the date of remission/stable disease or progression. Of the 1002 patients with f-NHL identified, 268 progressed and 734 did not. The mean overall costs PPPM over the 6-month follow-up period were significantly higher for patients with PD versus non-PD ($3527 vs. $860; difference = $2667; p < 0.001). This cost difference persisted within all resource categories evaluated. Results of this study indicate that therapies which delay progression for patients with f-NHL may result in potential cost savings. PMID:21745172

Umbilical Hernia in Peritoneal Dialysis Patients: Surgical Treatment and Risk Factors.

PubMed

Banshodani, Masataka; Kawanishi, Hideki; Moriishi, Misaki; Shintaku, Sadanori; Ago, Rika; Hashimoto, Shinji; Nishihara, Masahiro; Tsuchiya, Shinichiro

2015-12-01

No previous reports have focused on surgical treatments and risk factors of umbilical hernia alone in peritoneal dialysis (PD) patients. Herein, we evaluated the treatments and risk factors. A total of 411 PD patients were enrolled. Of the 15 patients with umbilical hernia (3.6%), six underwent hernioplasty. There was no recurrence in five patients treated with tension-free hernioplasty. The mean PD vintage after onset of hernia in the hernioplasty group tended to be longer than that in the non-hernioplasty group. An incarcerated hernia occurred in one non-hernioplasty patient. Although the incidence was significantly higher among women (P = 0.02), female sex was not a risk factor for umbilical hernia (P = 0.08). Our findings suggest that umbilical hernias should be repaired for continuing PD. Furthermore, there were no significant risk factors for umbilical hernia in PD patients. Future studies with larger sample groups are required to elucidate these risk factors. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Preoperative clinical and diagnostic characteristics of patients who require delayed IPP after primary Peyronies repair.

PubMed

Alphs, Hannah H; Navai, Neema; Köhler, Tobias S; McVary, Kevin T

2010-03-01

Penile vascular abnormalities occur in a high proportion of patients with Peyronie's disease (PD). Penile duplex ultrasonography (PDU) and dynamic infusion cavernosometry and cavernosography (DICC) are tools that can be used to help tailor individualized treatment for patients undergoing surgical intervention for their PD. However, precisely which parameters can be used to predict those patients with PD at risk for developing erectile dysfunction (ED) after intervention without inflatable penile prosthesis (IPP) has not been previously elucidated. To evaluate preoperative vascular parameters that predispose PD patients for developing ED after intervention without IPP. Twenty-six patients receiving surgical intervention for their PD at a single center were retrospectively identified. Of these, 11 (42.3%) opted for primary repair without placement of an IPP. Three (27.2%) of these 11 patients went on to develop ED postoperatively. We compared various demographic, PDU, and DICC parameters between patients who did and did not fail primary repair of their PD. Mean age and follow-up of patients who went on to develop ED after repair of PD without IPP were not significantly different (P < 0.05). Resistive index (RI) and end diastolic volume were significantly different between these two groups (P < 0.05), while peak systolic volume, flow to maintain, and pressure decay were not significantly different. An RI cutoff of <0.80 was found to identify all patients who would later develop ED and fail primary repair without IPP. Penile vascular assessment can aid in counseling patients about their risk of developing delayed ED after primary repair of PD. In our cohort of patients, PDU provided preoperative risk stratification for postoperative erectile dysfunction in men undergoing Peyronie's repair without IPP. We propose the prospective study of an RI cutoff to identify patients at risk of failing primary PD repair without IPP.

Economic Evaluation of Urgent-Start Peritoneal Dialysis Versus Urgent-Start Hemodialysis in the United States

PubMed Central

Liu, Frank Xiaoqing; Ghaffari, Arshia; Dhatt, Harman; Kumar, Vijay; Balsera, Cristina; Wallace, Eric; Khairullah, Quresh; Lesher, Beth; Gao, Xin; Henderson, Heather; LaFleur, Paula; Delgado, Edna M.; Alvarez, Melissa M.; Hartley, Janett; McClernon, Marilyn; Walton, Surrey; Guest, Steven

2014-01-01

Abstract Patients presenting late in the course of kidney disease who require urgent initiation of dialysis have traditionally received temporary vascular catheters followed by hemodialysis. Recent changes in Medicare payment policy for dialysis in the USA incentivized the use of peritoneal dialysis (PD). Consequently, the use of more expeditious PD for late-presenting patients (urgent-start PD) has received new attention. Urgent-start PD has been shown to be safe and effective, and offers a mechanism for increasing PD utilization. However, there has been no assessment of the dialysis-related costs over the first 90 days of care. The objective of this study was to characterize the costs associated with urgent-start PD, urgent-start hemodialysis (HD), or a dual approach (urgent-start HD followed by urgent-start PD) over the first 90 days of treatment from a provider perspective. A survey of practitioners from 5 clinics known to use urgent-start PD was conducted to provide inputs for a cost model representing typical patients. Model inputs were obtained from the survey, literature review, and available cost data. Sensitivity analyses were also conducted. The estimated per patient cost over the first 90 days for urgent-start PD was $16,398. Dialysis access represented 15% of total costs, dialysis services 48%, and initial hospitalization 37%. For urgent-start HD, total per patient costs were $19,352, and dialysis access accounted for 27%, dialysis services 42%, and initial hospitalization 31%. The estimated cost for dual patients was $19,400. Urgent-start PD may offer a cost saving approach for the initiation of dialysis in eligible patients requiring an urgent-start to dialysis. PMID:25526471

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson’s Disease Patients

PubMed Central

Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H.; Caviness, John N.; Shill, Holly A.; Sabbagh, Marwan; Samanta, Johan E.; Sue, Lucia I.; Beach, Thomas G.

2015-01-01

Dysphagia is common in Parkinson’s disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia. PMID:26041249

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson's Disease Patients.

PubMed

Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H; Caviness, John N; Shill, Holly A; Sabbagh, Marwan; Samanta, Johan E; Sue, Lucia I; Beach, Thomas G

2015-08-01

Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy

PubMed Central

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

ABSTRACT Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation (mPD-1) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = −0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35–4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16–3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies. PMID:27853645

The epidemiology, consequences and management of periodontal disease in older adults.

PubMed

Boehm, Tobias K; Scannapieco, Frank A

2007-09-01

This review summarizes the literature on periodontal disease (PD) in older adults. The authors focused on significant sequelae of PD and therapy in this population. The authors conducted a search on PubMed for human studies using the terms "periodontal disease OR periodontitis" and "older adults." They retrieved 649 articles and excluded studies that had poor experimental design. For each topic of the review, they selected one to three of the most recent studies or reviews for inclusion and cited classic articles where appropriate. PD is a common oral chronic inflammatory disease often found in older adults. In older patients, PD may lead to root caries, impaired eating and socialization. It also may increase patients' risk of developing systemic diseases such as diabetes mellitus, lung disease, heart disease and stroke. Treatment is not limited by chronological age but depends on the patient's medical and emotional status and the availability of financial resources. General dentists usually can treat the majority of older people with mild or moderate PD. For older adults who are medically compromised and dependent, the literature supports treatment that prevents PD progression.

Propofol Requirement for Induction of Unconsciousness Is Reduced in Patients with Parkinson's Disease: A Case Control Study

PubMed Central

Xu, Xiao-ping; Yu, Xi-ya; Wu, Xi; Hu, Xiao-wu; Chen, Jian-chun; Li, Jin-bao; Deng, Xiao-ming

2015-01-01

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, but whether the neurodegenerative process influences the pharmacodynamics of propofol remains unclear. We aimed to evaluate the effect of PD on pharmacodynamics of propofol. A total of 31 PD patients undergoing surgical treatment (PD group) and 31 pair-controlled non-PD patients undergoing intracranial surgery (NPD group) were recruited to investigate the propofol requirement for unconsciousness induction. Unconsciousness was induced in all patients with target-controlled infusion of propofol. The propofol concentration at which unconsciousness was induced was compared between the two groups. EC50 and EC95 were calculated as well. Demographic data, bispectral index, and hemodynamic values were comparable between PD and NPD groups. The mean target concentration of propofol when unconsciousness was achieved was 2.32 ± 0.38 μg/mL in PD group, which was significantly lower than that in NPD group (2.90 ± 0.35 μg/mL). The EC50 was 2.05 μg/mL (95% CI: 1.85–2.19 μg/mL) in PD group, much lower than the 2.72 μg/mL (95% CI: 2.53–2.88 μg/mL) in NPD group. In conclusion, the effective propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in PD patients. (This trial is registered with NCT01998204.) PMID:26495319

The effect of speed-accuracy strategy on response interference control in Parkinson's disease.

PubMed

Wylie, S A; van den Wildenberg, W P M; Ridderinkhof, K R; Bashore, T R; Powell, V D; Manning, C A; Wooten, G F

2009-07-01

Studies that used conflict paradigms such as the Eriksen Flanker task show that many individuals with Parkinson's disease (PD) have pronounced difficulty resolving the conflict that arises from the simultaneous activation of mutually exclusive responses. This finding fits well with contemporary views that postulate a key role for the basal ganglia in action selection. The present experiment aims to specify the cognitive processes that underlie action selection deficits among PD patients in the context of variations in speed-accuracy strategy. PD patients (n=28) and healthy controls (n=17) performed an arrow version of the flanker task under task instructions that either emphasized speed or accuracy of responses. Reaction time (RT) and accuracy rates decreased with speed compared to accuracy instructions, although to a lesser extent for the PD group. Differences in flanker interference effects among PD and healthy controls depended on speed-accuracy strategy. Compared to the healthy controls, PD patients showed larger flanker interference effects under speed stress. RT distribution analyses suggested that PD patients have greater difficulty suppressing incorrect response activation when pressing for speed. These initial findings point to an important interaction between strategic and computational aspects of interference control in accounting for cognitive impairments of PD. The results are also compatible with recent brain imaging studies that demonstrate basal ganglia activity to co-vary with speed-accuracy adjustments.

A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer

PubMed Central

Wang, Cuihua; Yu, Xuetao; Wang, Wei

2016-01-01

Abstract Background: Nonsmall cell lung cancer (NSCLC)-patients treated with standard chemotherapy experienced progression rapidly. A novel therapy based on programed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors showed an increasing potential in several malignancies including advanced NSCLC. Objectives: This article is a meta-analysis aiming to systematically evaluate the efficacy and safety profiles of PD-1/PD-L1 agents in patients with NSCLC. Data sources: Data were collected from eligible studies searched from PubMed, ScienceDirect, and Web of Science. Synthesis methods: Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1/PD-L1 inhibitors versus docetaxel, pooled odds ratio (OR) was calculated for objective response rate (ORR). The overall frequency was estimated for 1-year OS, 1-year progression-free survival, and ORR. A subgroup analysis among NSCLC patients tested with different epidermal growth factor receptor (EGFR) status was also performed to figure out the relationship between EGFR status and efficacy of PD-1/PD-L1 therapies. OR for occurrence of any grade and grade 3 to 5 treatment-related adverse effect was calculated for evaluating the safety of PD-1/PD-L1 therapies. Results: Nine studies were included in this analysis. The pooled HRs for OS and PFS were 0.68 (95% confidence interval [CI] 0.61–0.75) and 0.83 (95% CI 0.75–0.91), respectively, the pooled OR for ORR was 1.83 (95% CI 1.41–2.36), indicating a significant improvement in OS, PFS, and ORR. In the results of subgroup analysis, the HR for OS in NSCLC patients was 1.05 (95% CI 0.69–1.59) in patients with mutant EGFR and 0.66 (95% CI 0.57–0.77) in patients with wild-type EGFR status. OR for occurrence was 0.36 (95% CI 0.28–0.46) in any grade treatment-related adverse effect and 0.18 (95% CI 0.14–0.22) in grade 3 to 5 treatment-related adverse effect, suggesting a superior safety profile of PD-1/PD-L1 inhibitors. Conclusion: The PD-1/PD-L1 therapy significantly prolonged the OS and improved the ORR, simultaneously lowering the treatment-related adverse effect events versus docetaxel. PMID:28033249

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson's disease progression.

PubMed

Santos-García, Diego; Mir, Pablo; Cubo, Esther; Vela, Lydia; Rodríguez-Oroz, Mari Cruz; Martí, Maria José; Arbelo, José Matías; Infante, Jon; Kulisevsky, Jaime; Martínez-Martín, Pablo

2016-02-25

Parkinson's disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression. Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson's Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson's Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson's disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Public/Private. COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers.

Comorbidity of personality disorders and attention-deficit hyperactivity disorder in adults.

PubMed

Irastorza Eguskiza, Luis Javier; Bellón, Jose M; Mora, María

2016-03-08

A high comorbidity has been observed among attention-deficit hyperactivity disorder (ADHD) and categorical personality disorders (PD). A study is conducted on the dimensional traits associated with ADHD and PD, in order to determine whether there are any differences. A cross-sectional study was conducted on 78 outpatients attending a Mental Health Clinic in Arganda (Madrid) from January 2013 to June 2015. ADHD diagnosis was evaluated with the CAARS, the CAADID, and the WURS scales, and the PD with the SCID-II-DSM-IV questionnaire. None of the patients were receiving any stimulant or atomoxetine before the study, and all patients signed the informed consent before the study. A high comorbidity was found with all PD clusters, especially with hyperactive and combined type ADHD. Depressive PD was associated with inattentive ADHD. In spite of using a questionnaire to evaluate PD, some differences can be observed between specific ADHD types and PD. More studies are needed to investigate dimensional personality traits in order to improve the diagnosis and therapeutics goals. Copyright © 2016 SEP y SEPB. Published by Elsevier España. All rights reserved.

Dysphagia in Parkinson's Disease.

PubMed

Suttrup, Inga; Warnecke, Tobias

2016-02-01

More than 80 % of patients with Parkinson's disease (PD) develop dysphagia during the course of their disease. Swallowing impairment reduces quality of life, complicates medication intake and leads to malnutrition and aspiration pneumonia, which is a major cause of death in PD. Although the underlying pathophysiology is poorly understood, it has been shown that dopaminergic and non-dopaminergic mechanisms are involved in the development of dysphagia in PD. Clinical assessment of dysphagia in PD patients is challenging and often delivers unreliable results. A modified water test assessing maximum swallowing volume is recommended to uncover oropharyngeal dysphagia in PD. PD-specific questionnaires may also be useful to identify patients at risk for swallowing impairment. Fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing study are both considered to be the gold standard for evaluation of PD-related dysphagia. In addition, high-resolution manometry may be a helpful tool. These instrumental methods allow a reliable detection of aspiration events. Furthermore, typical patterns of impairment during the oral, pharyngeal and/or esophageal swallowing phase of PD patients can be identified. Therapy of dysphagia in PD consists of pharmacological interventions and swallowing treatment by speech and language therapists (SLTs). Fluctuating dysphagia with deterioration during the off-state should be treated by optimizing dopaminergic medication. The methods used during swallowing treatment by SLTs shall be selected according to the individual dysphagia pattern of each PD patient. A promising novel method is an intensive training of expiratory muscle strength. Deep brain stimulation does not seem to have a clinical relevant effect on swallowing function in PD. The goal of this review is giving an overview on current stages of epidemiology, pathophysiology, diagnosis, and treatment of PD-associated dysphagia, which might be helpful for neurologists, speech-language therapists, and other clinicians in their daily work with PD patients and associated swallowing difficulties. Furthermore areas with an urgent need for future clinical research are identified.

Palliative care for patients with Parkinson's disease: study protocol for a mixed methods study.

PubMed

Lennaerts, Herma; Groot, Marieke; Steppe, Maxime; van der Steen, Jenny T; Van den Brand, Marieke; van Amelsvoort, Dorian; Vissers, Kris; Munneke, Marten; Bloem, Bastiaan R

2017-11-25

Parkinson's disease (PD) is a chronic, progressive neurological disorder with many intractable consequences for patients and their family caregivers. Little is known about the possibilities that palliative care could offer to patients and their proxies. Guidelines strongly recommend palliative care to improve the quality of life and - if needed - the quality of dying. However, providing palliative care to persons with PD involves specific challenges. For example, a timely initiation of palliative interventions is difficult because due to the gradually progressive nature of PD, there is often no clear marker for the transition from curative towards palliative care. Furthermore, there is little evidence to indicate which palliative care interventions are effective. Here, we describe the contours of a study that aims to examine the experiences of patients, (bereaved) family caregivers and professionals, with the aim of improving our knowledge about palliative care needs in PD. We will perform a mixed methods study to evaluate the experiences of patients, (bereaved) family caregivers and palliative care professionals. In this study, we focus on Quality of Life, Quality of Care, perceived symptoms, caregiver burden and collaboration between professionals. In phase 1, we will retrospectively explore the views of bereaved family caregivers and professionals by conducting individual interviews and focus group interviews. In phase 2, 5-15 patients with PD and their family caregiver will be followed prospectively for 8-12 months. Data collection will involve semi-structured interviews and questionnaires at three consecutive contact moments. Qualitative data will be audio recorded, transcribed and analyzed using CAQDAS. If patients pass away during the study period, a bereavement interview will be done with the closest family caregiver. This study will offer a broad perspective on palliative care, and the results can be used to inform a palliative care protocol for patients with PD. By describing the experiences of patients, (bereaved) family caregivers and professionals with palliative care, this investigation will also establish an important ground for future intervention research.

Soluble PD-L1 with PD-1-binding capacity exists in the plasma of patients with non-small cell lung cancer.

PubMed

Takeuchi, Masahiro; Doi, Tomomitsu; Obayashi, Kunie; Hirai, Ayako; Yoneda, Kazue; Tanaka, Fumihiro; Iwai, Yoshiko

2018-04-01

PD-L1 is one of the important immune checkpoint molecules that can be targeted by cancer immunotherapies. PD-L1 has a soluble form (sPD-L1) and a membrane-bound form (mPD-L1). Conventional enzyme-linked immunosorbent assay (ELISA) systems can detect sPD-L1 using anti-PD-L1 capture antibody through the antigen-antibody reaction, but cannot evaluate the quality and function of sPD-L1. In this study, we developed a novel ELISA system for the detection and quantification of sPD-L1 with PD-1-binding capacity (bsPD-L1). To capture bsPD-L1 through the ligand-receptor reaction, the anti-PD-L1 capture antibody in the conventional ELISA was replaced with PD-1-Ig fusion protein in the new ELISA. The new ELISA could detect bsPD-L1 in 29 out of 75 plasma samples from patients with non-small cell lung cancer (NSCLC), with higher sensitivity and frequency than the conventional ELISA. The western blot analysis showed that sPD-L1 in the plasma was glycosylated. Treatment of the samples with glycosidase reduced the absorbance determined by the new ELISA but had no effect on the absorbance determined by the conventional ELISA. These results suggest that glycosylation of sPD-L1 is important for its binding to the immobilized PD-1 in the new ELISA. Our new ELISA system may be useful for the evaluation of functional sPD-L1 with PD-1-binding capacity in cancer patients. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Automatic Online Motor Control Is Intact in Parkinson's Disease With and Without Perceptual Awareness.

PubMed

Merritt, Kate E; Seergobin, Ken N; Mendonça, Daniel A; Jenkins, Mary E; Goodale, Melvyn A; MacDonald, Penny A

2017-01-01

In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson's disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients ( n = 14) and healthy controls ( n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls'. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses.

Automatic Online Motor Control Is Intact in Parkinson’s Disease With and Without Perceptual Awareness

PubMed Central

Seergobin, Ken N.; Mendonça, Daniel A.

2017-01-01

Abstract In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson’s disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients (n = 14) and healthy controls (n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls’. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses. PMID:29085900

Patients with Parkinson's disease display a dopamine therapy related negative bias and an enlarged range in emotional responses to facial emotional stimuli.

PubMed

Lundqvist, Daniel; Svärd, Joakim; Michelgård Palmquist, Åsa; Fischer, Håkan; Svenningsson, Per

2017-09-01

The literature on emotional processing in Parkinson's disease (PD) patients shows mixed results. This may be because of various methodological and/or patient-related differences, such as failing to adjust for cognitive functioning, depression, and/or mood. In the current study, we tested PD patients and healthy controls (HCs) using emotional stimuli across a variety of tasks, including visual search, short-term memory (STM), categorical perception, and emotional stimulus rating. The PD and HC groups were matched on cognitive ability, depression, and mood. We also explored possible relationships between task results and antiparkinsonian treatment effects, as measured by levodopa equivalent dosages (LED), in the PD group. The results show that PD patients use a larger emotional range compared with HCs when reporting their impression of emotional faces on rated emotional valence, arousal, and potency. The results also show that dopaminergic therapy was correlated with stimulus rating results such that PD patients with higher LED scores rated negative faces as less arousing, less negative, and less powerful. Finally, results also show that PD patients display a general slowing effect in the visual search tasks compared with HCs, indicating overall slowed responses. There were no group differences observed in the STM or categorical perception tasks. Our results indicate a relationship between emotional responses, PD, and dopaminergic therapy, in which PD per se is associated with stronger emotional responses, whereas LED levels are negatively correlated with the strength of emotional responses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Gambling behavior in Parkinson's Disease: Impulsivity, reward mechanism and cortical brain oscillations.

PubMed

Balconi, Michela; Angioletti, Laura; Siri, Chiara; Meucci, Nicoletta; Pezzoli, Gianni

2018-03-20

Psychopathological components, such as reward sensitivity and impulsivity, and dopaminergic treatment are crucial characteristics related to the development of Pathological Gambling (PG) in Parkinson's Disease (PD). The aim of the present study is to investigate the differences in decision-making in PD patients with or without PG considering both neurophysiological and behavioral aspects. The IOWA Gambling Task (IGT) and electroencephalographic (EEG) activity were considered to elucidate the decision and post-feedback processes in PG. The sample included fifty-two PD patients, divided in three groups: 17 PD patients with active gambling behavior (PD Gamblers, PDG); 15 PD patients who remitted from PG (PD Non-Gamblers, PDNG); and a Control Group (CG) composed by 20 patients with PD only. EEG and IGT performance were recorded during decision and post-feedback phase. Results showed worse performance and an increase of the low frequency bands in the frontal area for the PDG group compared to the other two groups. In addition, higher BAS (Behavioral Activation System) and BIS-11 (Barratt Impulsiveness Scale) personality components were correlated to groups' behavioral response. These results show an anomalous behavioral (IGT) and cortical response of PDG patients related to their inability to use adequate control mechanisms during a decision-making task where reward mechanisms (BAS) and impulsivity (BIS-11) are relevant. Copyright © 2018 Elsevier B.V. All rights reserved.

Multiple White Matter Volume Reductions in Patients with Panic Disorder: Relationships between Orbitofrontal Gyrus Volume and Symptom Severity and Social Dysfunction

PubMed Central

Konishi, Jun; Asami, Takeshi; Hayano, Fumi; Yoshimi, Asuka; Hayasaka, Shunsuke; Fukushima, Hiroshi; Whitford, Thomas J.; Inoue, Tomio; Hirayasu, Yoshio

2014-01-01

Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p<0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD. PMID:24663245

Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study

PubMed Central

Healy, Daniel G; Falchi, Mario; O'Sullivan, Sean S; Bonifati, Vincenzo; Durr, Alexandra; Bressman, Susan; Brice, Alexis; Aasly, Jan; Zabetian, Cyrus P; Goldwurm, Stefano; Ferreira, Joaquim J; Tolosa, Eduardo; Kay, Denise M; Klein, Christine; Williams, David R; Marras, Connie; Lang, Anthony E; Wszolek, Zbigniew K; Berciano, Jose; Schapira, Anthony HV; Lynch, Timothy; Bhatia, Kailash P; Gasser, Thomas; Lees, Andrew J; Wood, Nicholas W

2008-01-01

Summary Background Mutations in LRRK2, the gene that encodes leucine-rich repeat kinase 2, are a cause of Parkinson's disease (PD). The International LRRK2 Consortium was established to answer three key clinical questions: can LRRK2-associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2? Methods Researchers from 21 centres across the world collaborated on this study. The frequency of the common LRRK2 Gly2019Ser mutation was estimated on the basis of data from 24 populations worldwide, and the penetrance of the mutation was defined in 1045 people with mutations in LRRK2 from 133 families. The LRRK2 phenotype was defined on the basis of 59 motor and non-motor symptoms in 356 patients with LRRK2-associated PD and compared with the symptoms of 543 patients with pathologically proven idiopathic PD. Findings Six mutations met the consortium's criteria for being proven pathogenic. The frequency of the common LRRK2 Gly2019Ser mutation was 1% of patients with sporadic PD and 4% of patients with hereditary PD; the frequency was highest in the middle east and higher in southern Europe than in northern Europe. The risk of PD for a person who inherits the LRRK2 Gly2019Ser mutation was 28% at age 59 years, 51% at 69 years, and 74% at 79 years. The motor symptoms (eg, disease severity, rate of progression, occurrence of falls, and dyskinesia) and non-motor symptoms (eg, cognition and olfaction) of LRRK2-associated PD were more benign than those of idiopathic PD. Interpretation Mutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD. However, this knowledge should be applied with caution in the diagnosis and counselling of patients. Funding UK Medical Research Council; UK Parkinson's Disease Society; UK Brain Research Trust; Internationaal Parkinson Fonds; Volkswagen Foundation; National Institutes of Health: National Institute of Neurological Disorders and Stroke and National Institute of Aging; Udall Parkinson's Disease Centre of Excellence; Pacific Alzheimer Research Foundation Centre; Italian Telethon Foundation; Fondazione Grigioni per il Morbo di Parkinson; Michael J Fox Foundation for Parkinson's Research; Safra Global Genetics Consortium; US Department of Veterans Affairs; French Agence Nationale de la Recherche. PMID:18539534

P wave dispersion in patients with hypochondriasis.

PubMed

Atmaca, Murad; Korkmaz, Hasan; Korkmaz, Sevda

2010-11-26

P wave dispersion (Pd), defined as the difference between the maximum and the minimum P wave duration, has been associated with anxiety. Thus, we wondered whether Pd in hypochondriasis which is associated with anxiety differed from that in healthy controls. Pd was measured in 30 hypochondriac patients and same number of physically and mentally healthy age- and gender-matched controls. Hamilton Depression Rating (HDRS) and Hamilton Anxiety Rating Scales (HARS) were scored. The heart rate and left atrium (LA) sizes were not significantly different between groups. However, both Pmax and Pmin values of the patients were significantly higher than those of healthy controls. As for the main variable investigated in the present study, the corrected Pd was significantly longer in the patient group compared to control group. On the basis of this study, we can conclude that Pd may be related to hypochondriasis though our sample is too small to allow us to obtain a clear conclusion. Future studies with larger sample evaluating the effects of treatment are required. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Hospital care for mental health and substance abuse conditions in Parkinson's disease.

PubMed

Willis, Allison W; Thibault, Dylan P; Schmidt, Peter N; Dorsey, E Ray; Weintraub, Daniel

2016-12-01

The objective of this study was to examine mental health conditions among hospitalized individuals with Parkinson's disease in the United States. This was a serial cross-sectional study of hospitalizations of individuals aged ≥60 identified in the Nationwide Inpatient Sample dataset from 2000 to 2010. We identified all hospitalizations with a diagnosis of PD, alcohol abuse, anxiety, bipolar disorder, depression, impulse control disorders, mania, psychosis, substance abuse, and attempted suicide/suicidal ideation. National estimates of each mental health condition were compared between hospitalized individuals with and without PD. Hierarchical logistic regression models determined which inpatient mental health diagnoses were associated with PD, adjusting for demographic, payer, geographic, and hospital characteristics. We identified 3,918,703 mental health and substance abuse hospitalizations. Of these, 2.8% (n = 104, 437) involved a person also diagnosed with PD. The majority of mental health and substance abuse patients were white (86.9% of PD vs 83.3% of non-PD). Women were more common than men in both groups (male:female prevalence ratio, PD: 0.78, 0.78-0.79, non-PD: 0.58, 0.57-0.58). Depression (adjusted odds ratio 1.32, 1.31-1.34), psychosis (adjusted odds ratio 1.25, 1.15-1.33), bipolar disorder (adjusted odds ratio 2.74, 2.69-2.79), impulse control disorders (adjusted odds ratio 1.51, 1.31-1.75), and mania (adjusted odds ratio 1.43, 1.18-1.74) were more likely among PD patients, alcohol abuse was less likely (adjusted odds ratio 0.26, 0.25-0.27). We found no PD-associated difference in suicide-related care. PD patients have unique patterns of acute care for mental health and substance abuse. Research is needed to guide PD treatment in individuals with pre-existing psychiatric illnesses, determine cross provider reliability of psychiatric diagnoses in PD patients, and inform efforts to improve psychiatric outcomes. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

An observational clinical and video-polysomnographic study of the effects of rotigotine in sleep disorder in Parkinson's disease.

PubMed

Wang, Yan; Yang, Yue-Chang; Lan, Dan-Mei; Wu, Hui -Juan; Zhao, Zhong-Xin

2017-05-01

Sleep disturbance is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopamine agonists influence nocturnal sleep in PD, particularly in sleep laboratory data to measure sleep parameters and their changes objectively. The goal of this open-label study was to objectively evaluate the effect of rotigotine on sleep in PD patients by video-polysomnographic methods. A total of 25 PD patients with complaints of nocturnal sleep impairment were enrolled. The sleep quality before and after stable rotigotine therapy was evaluated subjectively through questionnaire assessments and objectively measured by video-polysomnographic methods. The Parkinsonism, depression, anxiety, and quality of life of PD patients were also evaluated through questionnaire assessments. At the end of rotigotine treatment, the PD daytime functioning, motor performance, depression, subjective quality of sleep, and the quality of life improved. Video-polysomnographic analysis showed that the sleep efficiency and stage N1% were increased, while the sleep latency, wake after sleep onset, and the periodic leg movements in sleep index were decreased after rotigotine treatment. Video-polysomnographic analysis confirmed the subjective improvement of sleep after rotigotine treatment. This observation suggests that in PD rotigotine is a treatment option for patients complaining from sleep disturbances.

Risk of immune-related colitis with PD-1/PD-L1 inhibitors vs chemotherapy in solid tumors: systems assessment.

PubMed

Su, Qiang; Zhang, Xiaochen; Shen, Xinhua; Hou, Yanli; Sun, Zhigang; Gao, Zu Hua

2018-01-01

Background: We performed a meta-analysis to evaluate the risk of immune-related colitis associated with PD1/PD-L1 inhibitors as compared to chemotherapy in solid tumor patients. Methods: Eligible studies were identified through a comprehensive search of multiple databases and included solid tumor patients in randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors. The data was analyzed by Stata version 12.0 software. Results: After exclusion of ineligible studies, 11 clinical trials were considered eligible for the meta-analysis, including 5751 patients. Compared with chemotherapy, the risk ratios (RRs) of all-grade colitis were significant for the PD-1 inhibitor subgroup (RR 2.69, 95% confidence interval (CI): 1.15-6.29, p=0.023), and for pembrolizumab subgroup (RR 3.17, 95% CI: 1.08-9.37, p=0.037), but not for nivolumab treatment and PD-L1 inhibitor (atezolizumab) treatment (RR 2.05, 95% CI: 0.52-8.13, p=0.305; RR 4.75,95% CI: 0.56-40.50, p=0.154, respectively). The RR of all-grade colitis was significant for PD-1/PD-L1 inhibitor in NSCLC (RR 4.34, 95% CI: 1.37-13.82, p=0.013), and not significant in melanoma (RR 2.11, 95% CI: 0.54-8.34, p=0.285). Moreover, the RRs of all-grade diarrhea were significant for the PD-1 inhibitor subgroup (RR 0.61, 95% CI: 0.44-0.83, p=0.002), for the nivolumab subgroup (RR 0.54, 95% CI: 0.34-0.87, p=0.012), and for atezolizumab subgroup (RR 0.48, 95% CI: 0.25-0.89, p=0.021). The RR of high-grade diarrhea was significant for atezolizumab subgroup (RR 0.34, 95% CI: 0.12-0.94, p=0.037). Conclusions: Our meta-analysis demonstrates that compared with chemotherapy, pembrolizumab may result in a higher risk of all-grade immune-mediated colitis. PD-1/PD-L1 inhibitor treatment in NSCLC patients, but not in melanoma patients, increases the risk of all-grade colitis incidence.

Refining diagnosis of Parkinson's disease with deep learning-based interpretation of dopamine transporter imaging.

PubMed

Choi, Hongyoon; Ha, Seunggyun; Im, Hyung Jun; Paek, Sun Ha; Lee, Dong Soo

2017-01-01

Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies.

Advanced Theory of Mind in patients at early stage of Parkinson's disease.

PubMed

Yu, Rwei-Ling; Wu, Ruey-Meei; Chiu, Ming-Jang; Tai, Chun-Hwei; Lin, Chin-Hsien; Hua, Mau-Sun

2012-01-01

Advanced Theory of Mind (ToM) refers to the sophisticated ability to infer other people's thoughts, intentions, or emotions in social situations. With appropriate advanced ToM, one can behave well in social interactions and can understand the intention of others' behavior. Prefrontal cortex plays a vital role in this ability, as shown in functional brain imaging and lesion studies. Considering the primary neuropathology of Parkinson's disease (PD) involving the frontal lobe system, patients with PD are expected to exhibit deficits in advanced ToM. However, few studies on this issue have been explored, and whether advanced ToM is independent of executive functions remains uncertain. Thirty-nine early non-demented PD patients and 40 normal control subjects were included. Both groups were matched in age, level of education, and verbal intelligence quotient. Each participant received advanced ToM, executive functions, and verbal intelligence quotient tests. We discovered that the performance of the PD patients on the Cartoon ToM task was significantly poorer than that of their normal counterparts. Correlation analysis revealed that performance scores of advanced ToM in PD patients were significantly associated with their executive functions scores; however, this is not the case for normal controls. We conclude that dysfunction of advanced ToM develops in early PD patients, who require more cognitive abilities than their normal counterparts to generate advanced ToM. Our findings might be helpful in developing educational and medical care programs for PD patients in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Taste responses in patients with Parkinson's disease

PubMed Central

Sienkiewicz-Jaros..., H; Scinska, A; Kuran, W; Ryglewicz, D; Rogowski, A; Wrobel, E; Korkosz, A; Kukwa, A; Kostowski, W; Bienkowski, P

2005-01-01

Objective: Preclinical studies indicate that dopaminergic transmission in the basal ganglia may be involved in processing of both pleasant and unpleasant stimuli. Given this, the aim of the present study was to assess taste responses to sweet, bitter, sour, and salty substances in patients with Parkinson's disease (PD). Methods: Rated intensity and pleasantness of filter paper discs soaked in sucrose (10–60%), quinine (0.025–0.5%), citric acid (0.25–4.0%), or sodium chloride (1.25–20%) solutions was evaluated in 30 patients with PD and in 33 healthy controls. Paper discs soaked in deionised water served as control stimuli. In addition, reactivity to 100 ml samples of chocolate and vanilla milk was assessed in both groups. Taste detection thresholds were assessed by means of electrogustometry. Sociodemographic and neuropsychiatric data, including cigarette smoking, alcohol consumption, tea and coffee drinking, depressive symptoms, and cognitive functioning were collected. Results: In general, perceived intensity, pleasantness, and identification of the sucrose, quinine, citric acid, or sodium chloride samples did not differ between the PD patients and controls. Intensity ratings of the filter papers soaked in 0.025% quinine were significantly higher in the PD patients compared with the control group. No inter-group differences were found in taste responses to chocolate and vanilla milk. Electrogustometric thresholds were significantly (p = 0.001) more sensitive in the PD patients. Conclusions: PD is not associated with any major alterations in responses to pleasant or unpleasant taste stimuli. Patients with PD may present enhanced taste acuity in terms of electrogustometric threshold. PMID:15607993

Manometric abnormalities of the oesophagus in patients with Parkinson's disease.

PubMed

Castell, J A; Johnston, B T; Colcher, A; Li, Q; Gideon, R M; Castell, D O

2001-08-01

Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of oropharyngeal function. Oesophageal abnormalities have not been previously demonstrated to correlate with dysphagia. The aim of the study was to determine if motor dysfunction of the oesophageal body correlates with dysphagia or disease severity in PD. Twenty-two patients with PD were assessed for the severity of their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All underwent oesophageal manometry. Dysphagia was present daily in 10 patients (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen patients had either complete aperistalsis or multiple simultaneous contractions (diffuse oesophageal spasm). These findings were significantly more common in patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to duration or severity of PD. We conclude that the presence of aperistalsis or multiple simultaneous contractions in the oesophagus does correlate with dysphagia and is independent of PD severity or duration. This may reflect selective involvement of either the dorsal motor nucleus of the vagus or the oesophageal myenteric plexus.

Degraded Impairment of Emotion Recognition in Parkinson's Disease Extends from Negative to Positive Emotions.

PubMed

Lin, Chia-Yao; Tien, Yi-Min; Huang, Jong-Tsun; Tsai, Chon-Haw; Hsu, Li-Chuan

2016-01-01

Because of dopaminergic neurodegeneration, patients with Parkinson's disease (PD) show impairment in the recognition of negative facial expressions. In the present study, we aimed to determine whether PD patients with more advanced motor problems would show a much greater deficit in recognition of emotional facial expressions than a control group and whether impairment of emotion recognition would extend to positive emotions. Twenty-nine PD patients and 29 age-matched healthy controls were recruited. Participants were asked to discriminate emotions in Experiment  1 and identify gender in Experiment  2. In Experiment  1, PD patients demonstrated a recognition deficit for negative (sadness and anger) and positive faces. Further analysis showed that only PD patients with high motor dysfunction performed poorly in recognition of happy faces. In Experiment  2, PD patients showed an intact ability for gender identification, and the results eliminated possible abilities in the functions measured in Experiment  2 as alternative explanations for the results of Experiment  1. We concluded that patients' ability to recognize emotions deteriorated as the disease progressed. Recognition of negative emotions was impaired first, and then the impairment extended to positive emotions.

Degraded Impairment of Emotion Recognition in Parkinson's Disease Extends from Negative to Positive Emotions

PubMed Central

Tien, Yi-Min; Huang, Jong-Tsun

2016-01-01

Because of dopaminergic neurodegeneration, patients with Parkinson's disease (PD) show impairment in the recognition of negative facial expressions. In the present study, we aimed to determine whether PD patients with more advanced motor problems would show a much greater deficit in recognition of emotional facial expressions than a control group and whether impairment of emotion recognition would extend to positive emotions. Twenty-nine PD patients and 29 age-matched healthy controls were recruited. Participants were asked to discriminate emotions in Experiment  1 and identify gender in Experiment  2. In Experiment  1, PD patients demonstrated a recognition deficit for negative (sadness and anger) and positive faces. Further analysis showed that only PD patients with high motor dysfunction performed poorly in recognition of happy faces. In Experiment  2, PD patients showed an intact ability for gender identification, and the results eliminated possible abilities in the functions measured in Experiment  2 as alternative explanations for the results of Experiment  1. We concluded that patients' ability to recognize emotions deteriorated as the disease progressed. Recognition of negative emotions was impaired first, and then the impairment extended to positive emotions. PMID:27555668

Immunotherapy for metastatic urothelial carcinoma: status quo and the future.

PubMed

Necchi, Andrea; Rink, Michael; Giannatempo, Patrizia; Raggi, Daniele; Xylinas, Evanguelos

2018-01-01

The treatment paradigm of urothelial carcinoma has been revolutionized by the advent of multiple anti-programmed-cell death-1/ligand-1 (PD-1/PD-L1) antibodies. Significant improvements have been obtained in the locally advanced or metastatic stage, which was lacking of therapeutic standards. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in this disease. Anti-PD-1/PD-L1 monoclonal antibodies have shown efficacy and safety in patients with urothelial carcinoma, regardless of their prognostic features. Efficacy was similar across different compounds, with objective responses that approximate 20%, with some differences favoring PD-L1-expressing patients. Typically, responding patients have good chances of achieving durable response, but biomarkers predictive of therapeutic effect are lacking. To date, evidences from randomized studies are limited to the second-line, postplatinum therapy. Despite the activity of PD-1/PD-L1 inhibitors is well established in metastatic urothelial carcinoma, multiple gray zones still exist regarding their optimal use in clinical practice. These uncertainties are related to patient and treatment-related criteria, to the optimal duration of treatment, including combination or sequence with standard chemotherapy. Special issues are represented by pseudoprogression or hyperprogression. Generally, enhanced predictive tools are needed and a myriad of further investigations are underway.

Altered moral decision-making in patients with idiopathic Parkinson's disease.

PubMed

Rosen, Jan B; Rott, Elisa; Ebersbach, Georg; Kalbe, Elke

2015-10-01

Moral decision-making essentially contributes to social conduct. Although patients with Parkinson's disease (PD) show deficits in (non-moral) decision making and related neuropsychological functions, i.e. executive functions, theory of mind (ToM), and empathy, moral decision-making has rarely been examined in PD patients. We examined possible alterations of moral decision-making and associated functions in PD. Twenty non-demented PD patients and 23 age- and education-matched healthy control participants were examined with tests that assess reasoning, executive functions (set-shifting and planning), ToM and empathy, decision-making under risk, and moral intuitions. Moral decision-making was assessed with a close-to-everyday moral dilemma paradigm that opposes socially oriented "altruistic" choices to self-beneficial "egoistic" choices in 20 moral dilemma short stories (10 high and 10 low emotional). Concurrently, electrodermal activity was recorded. PD patients made more egoistic moral decisions than healthy controls. Remarkably, while reasoning, planning and empathy correlated with moral decision-making in the control group, in the PD group neuropsychological functions and dopaminergic medication did not correlate with moral decisions. No evidence for reduced skin conductance responses in PD patients and no relationships between skin conductance responses and moral decisions were observed. This study provides evidence for moral decision-making dysfunctions in PD patients who made more egoistic moral decisions. As a possible underlying mechanism, reduced exercise of attentional control due to a dysfunctional interplay between the prefrontal cortex and the basal ganglia is discussed. Future research will have to determine the impact of PD patients' moral decision-making dysfunctions on everyday life and further determine correlates of the deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy?

PubMed

Tang, Fei; Zheng, Pan

2018-01-01

Antibody blockade of the PD-1/PD-L1 pathway has elicited durable antitumor responses in the therapy of a broad spectrum of cancers. PD-L1 is constitutively expressed in certain tumors and host immune cells, and its expression can be induced or maintained by many factors. The expression of PD-L1 on tumor tissues has been reported to be positively correlated with the efficacy of anti-PD-1/PD-L1 therapy in patients. However, multiple clinical trials indicate that patients with PD-L1-negative tumors also respond to this blockade therapy, which suggests the potential contribution of PD-L1 from host immune cells. Recently, six articles independently evaluated and verified the contributions of PD-L1 from tumor versus non-tumor cells in various mouse tumor models. These studies confirmed that PD-L1 on either tumor cells or host immune cells contributes to tumor escape, and the relative contributions of PD-L1 on these cells seem to be context-dependent. While both tumor- and host-derived PD-L1 can play critical roles in immune suppression, differences in tumor immunogenicity appear to underlie their relative importance. Notably, these reports highlight the essential roles of PD-L1 from host myeloid cells in negatively regulating T cell activation and limiting T cell trafficking. Therefore, comprehensive evaluating the global PD-L1 expression, rather than monitoring PD-L1 expression on tumor cells alone, should be a more accurate way for predicting responses in PD-1/PD-L1 blockade therapy in cancer patients.

Human leukocyte antigen variation and Parkinson’s disease

PubMed Central

Puschmann, Andreas; Verbeeck, Christophe; Heckman, Michael G.; Soto-Ortolaza, Alexandra I.; Lynch, Timothy; Jasinska-Myga, Barbara; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Uitti, Ryan J.; Wszolek, Zbigniew K.; Ross, Owen A.

2011-01-01

A role for the immune system in the pathogenesis of Parkinson’s Disease (PD) has previously been suggested. A recent genome-wide association (GWA) study identified an association between one single nucleotide polymorphism (SNP) in the human leucocyte antigen (HLA) region (HLA-DRA rs3129882) and PD in a population of American patients with European ancestry. In that study, the minor rs3129882 allele (G) was associated with an increased risk of PD under an additive model. Due to the increased likelihood of obtaining false positive results in GWA studies compared to studies conducted based on a hypothesis-driven approach, repeated validation of findings from GWA studies are necessary. Herein, we evaluated the association between rs3129882 and PD in three different Caucasian patient-control series (combined 1,313 patients and 1,305 controls) from the US, Ireland, and Poland. We observed no association (OR: 0.96, P=0.50) between rs3129882 and PD when analyzing our data under an additive or dominant model. In contrast, when examined under a recessive model, the GG genotype was observed to be protective in the Irish (OR: 0.55, P=0.008), Polish (OR: 0.67, P=0.040) and combined (OR: 0.75, P=0.006) patient-control series. In view of these diverging results, the exact role of genetic variation at the HLA region and susceptibility to PD remains to be resolved. PMID:21482477

Classical eyeblink conditioning in Parkinson's disease.

PubMed

Daum, I; Schugens, M M; Breitenstein, C; Topka, H; Spieker, S

1996-11-01

Patients with Parkinson's disease (PD) show impairments of a range of motor learning tasks, including tracking or serial reaction time task learning. Our study investigated whether such deficits would also be seen on a simple type of motor learning, classic conditioning of the eyeblink response. Medicated and unmediated patients with PD showed intact unconditioned eyeblink responses and significant learning across acquisition; the learning rates did not differ from those of healthy control subjects. The overall frequency of conditioned responses was significantly higher in the medicated patients with PD relative to control subjects, and there was also some evidence of facilitation in the unmedicated patients with PD. Conditioning of electrodermal and electrocortical responses was comparable in all groups. The findings are discussed in terms of enhanced excitability of brainstem pathways in PD and of the involvement of different neuronal circuits in different types of motor learning.

Problem-solving ability and comorbid personality disorders in depressed outpatients.

PubMed

Harley, Rebecca; Petersen, Timothy; Scalia, Margaret; Papakostas, George I; Farabaugh, Amy; Fava, Maurizio

2006-01-01

Major depressive disorder (MDD) is associated with poor problem-solving abilities. In addition, certain personality disorders (PDs) that are common among patients with MDD are also associated with limited problem-solving skills. Attempts to understand the relationship between PDs and problem solving can be complicated by the presence of acute MDD. Our objective in this study was to investigate the relationships between PDs, problem-solving skills, and response to treatment among outpatients with MDD. We enrolled 312 outpatients with MDD in an open, fixed-dose, 8-week fluoxetine trial. PD diagnoses were ascertained via structured clinical interview before and after fluoxetine treatment. Subjects completed the Problem-Solving Inventory (PSI) at both time points. We used analyses of covariance (ANCOVAs) to assess relationships between PD diagnoses and PSI scores prior to treatment. Subjects were divided into three groups: those with PD diagnoses that remained stable after fluoxetine treatment (N=91), those who no longer met PD criteria after fluoxetine treatment (N=119), and those who did not meet criteria for a PD at any time point in the study (N=95). We used multiple chi(2) analyses to compare rates of MDD response and remission between the three PD groups. ANCOVA was also used to compare posttreatment PSI scores between PD groups. Prior to fluoxetine treatment, patients with avoidant, dependent, narcissistic, and borderline PDs reported significantly worse problem-solving ability than did patients without any PDs. Only subjects with dependent PD remained associated with poorer baseline problem-solving reports after the effects of baseline depression severity were controlled. Patients with stable PD diagnoses had significantly lower rates of MDD remission. Across PD groups, problem solving improved as MDD improved. No significant differences in posttreatment problem-solving were found between PD groups after controlling for baseline depression severity, baseline PSI score, and response to treatment. Treatment with fluoxetine is less likely to lead to remission of MDD in patients with stable PDs. More study is needed to investigate causal links between PDs, problem solving, and MDD treatment response. Published 2006 Wiley-Liss, Inc.

Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

PubMed

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-11-01

The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas express PD-L1. Malignant effusions in this disease are characterized by the presence of tumor cells and CD3-positive T cells that highly express PD-L1. In addition, mesothelioma tumor cells are susceptible to ADCC by the anti-PD-L1 antibody avelumab. Published by Elsevier Inc.

Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

PubMed Central

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-01-01

INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T cells that highly express PD-L1. In addition, mesothelioma tumor cells are susceptible to ADCC by anti-PD-L1 antibody avelumab. PMID:27544053

Intact emotion recognition and experience but dysfunctional emotion regulation in idiopathic Parkinson's disease.

PubMed

Ille, Rottraut; Wabnegger, Albert; Schwingenschuh, Petra; Katschnig-Winter, Petra; Kögl-Wallner, Mariella; Wenzel, Karoline; Schienle, Anne

2016-02-15

A specific non-motor impairment in Parkinson's disease (PD) concerns difficulties to accurately identify facial emotions. Findings are numerous but very inconsistent, ranging from general discrimination deficits to problems for specific emotions up to no impairment at all. By contrast, only a few studies exist about emotion experience, altered affective traits and states in PD. To investigate the decoding capacity for affective facial expressions, affective experience of emotion-eliciting images and affective personality traits in PD. The study sample included 25 patients with mild to moderate symptom intensity and 25 healthy controls (HC) of both sexes. The participants were shown pictures of facial expressions depicting disgust, fear, and anger as well as disgusting and fear-relevant scenes. Additionally, they answered self-report scales for the assessment of affective traits. PD patients had more problems in controlling anger and disgust feelings than HC. Higher disgust sensitivity in PD was associated with lower functioning in everyday life and lower capacity to recognize angry faces. Furthermore, patients reported less disgust towards poor hygiene and spoiled food and they stated elevated anxiety. However, the clinical group displayed intact facial emotion decoding and emotion experience. Everyday life functionality was lowered in PD and decreased with stronger motor impairment. Furthermore, disease duration was negatively associated to correct classification of angry faces. Our data indicate that problems with emotion regulation may appear already in earlier disease stages of PD. By contrast, PD patients showed appropriate emotion recognition and experience. However, data also point to a deterioration of emotion recognition capacity with the course of the disease. Compensatory mechanisms in PD patients with less advanced disease are discussed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Altered white matter microarchitecture in the cingulum bundle in women with primary dysmenorrhea: A tract-based analysis study.

PubMed

Liu, Jixin; Liu, Hongjuan; Mu, Junya; Xu, Qing; Chen, Tao; Dun, Wanghuan; Yang, Jing; Tian, Jie; Hu, Li; Zhang, Ming

2017-09-01

Primary dysmenorrhea (PD), as characterized by painful menstrual cramps without organic causes, is associated with central sensitization and brain function changes. Previous studies showed the integrated role of the default mode network (DMN) in the pain connectome and its key contribution on how an individual perceives and copes with pain disorders. Here, we aimed to investigate whether the cingulum bundle connecting hub regions of the DMN was disrupted in young women with PD. Diffusion tensor imaging was obtained in 41 PD patients and 41 matched healthy controls (HC) during their periovulatory phase. The production of prostaglandins (PGs) was obtained in PD patients during their pain-free and pain phases. As compared with HC, PD patients had similar scores of pain intensity, anxiety, and depression in their pain-free phase. However, altered white matter properties mainly located in the posterior section of the cingulum bundle were observed in PD. Besides PGs being related to menstrual pain, a close relationship was found between the white matter properties of the cingulum bundle during the pain-free phase and the severity of the menstrual pain in PD patients. Our study suggested that PD had trait changes of white matter integrities in the cingulum bundle that persisted beyond the time of menstruation. We inferred that altered anatomical connections may lead to less-flexible communication within the DMN, and/or between the DMN and other pain-related brain networks, which may result in the central susceptibility to develop chronic pain conditions in PD's later life. Hum Brain Mapp 38:4430-4443, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Lack of post-exercise depression of corticospinal excitability in patients with Parkinson's disease.

PubMed

Khedr, E M; Galal, O; Said, A; Abd-elsameea, M; Rothwell, J C

2007-07-01

There is lack of clarity in the literature over whether patients with Parkinson's disease (PD) show the same post-exercise depression of corticospinal excitability as is usually observed in healthy control. This study set out to resolve the problem. Ten patients with idiopathic PD and 10 age-matched controls were included in this study. Each subject performed a submaximal sustained voluntary contraction of the right first dorsal interosseous muscle (FDI) for 10 min or until force could no longer be sustained. Resting motor threshold, motor-evoked potential (MEP), input-output curve, cortical silent period duration, interference pattern (IP) and M/F ratio were recorded at baseline, immediately after fatigue and after 20 min rest. Immediately after exercise, decreased MEP amplitude and increased cortical SP duration were observed in the control group whilst no such changes were observed in PD patients. The input-output curve was also significantly suppressed only in controls, but not in patients. The amplitude of IP was significantly reduced immediately after exercise in both PD patients and controls. Almost all these changes returned nearly to baseline values after 20 min rest. The amount of exercise was approximately equal in both groups because the effect on M-waves and EMG amplitude was similar. However, the expected decline in corticospinal excitability was absent in PD patients. The absence of this effect in PD patients may reflect reorganization of motor commands in response to basal ganglia deficit.

Challenging Postural Tasks Increase Asymmetry in Patients with Parkinson’s Disease

PubMed Central

Beretta, Victor Spiandor; Gobbi, Lilian Teresa Bucken; Lirani-Silva, Ellen; Simieli, Lucas; Orcioli-Silva, Diego; Barbieri, Fabio Augusto

2015-01-01

The unilateral predominance of Parkinson’s disease (PD) symptoms suggests that balance control could be asymmetrical during static tasks. Although studies have shown that balance control asymmetries exist in patients with PD, these analyses were performed using only simple bipedal standing tasks. Challenging postural tasks, such as unipedal or tandem standing, could exacerbate balance control asymmetries. To address this, we studied the impact of challenging standing tasks on postural control asymmetry in patients with PD. Twenty patients with PD and twenty neurologically healthy individuals (control group) participated in this study. Participants performed three 30s trials for each postural task: bipedal, tandem adapted and unipedal standing. The center of pressure parameter was calculated for both limbs in each of these conditions, and the asymmetry between limbs was assessed using the symmetric index. A significant effect of condition was observed, with unipedal standing and tandem standing showing greater asymmetry than bipedal standing for the mediolateral root mean square (RMS) and area of sway parameters, respectively. In addition, a group*condition interaction indicated that, only for patients with PD, the unipedal condition showed greater asymmetry in the mediolateral RMS and area of sway than the bipedal condition and the tandem condition showed greater asymmetry in the area of sway than the bipedal condition. Patients with PD exhibited greater asymmetry while performing tasks requiring postural control when compared to neurologically healthy individuals, especially for challenging tasks such as tandem and unipedal standing. PMID:26367032

Differential diagnosis between Parkinson's disease and essential tremor using the smartphone's accelerometer.

PubMed

Barrantes, Sergi; Sánchez Egea, Antonio J; González Rojas, Hernán A; Martí, Maria J; Compta, Yaroslau; Valldeoriola, Francesc; Simo Mezquita, Ester; Tolosa, Eduard; Valls-Solè, Josep

2017-01-01

The differential diagnosis between patients with essential tremor (ET) and those with Parkinson's disease (PD) whose main manifestation is tremor may be difficult unless using complex neuroimaging techniques such as 123I-FP-CIT SPECT. We considered that using smartphone's accelerometer to stablish a diagnostic test based on time-frequency differences between PD an ET could support the clinical diagnosis. The study was carried out in 17 patients with PD, 16 patients with ET, 12 healthy volunteers and 7 patients with tremor of undecided diagnosis (TUD), who were re-evaluated one year after the first visit to reach the definite diagnosis. The smartphone was placed over the hand dorsum to record epochs of 30 s at rest and 30 s during arm stretching. We generated frequency power spectra and calculated receiver operating characteristics curves (ROC) curves of total spectral power, to establish a threshold to separate subjects with and without tremor. In patients with PD and ET, we found that the ROC curve of relative energy was the feature discriminating better between the two groups. This threshold was then used to classify the TUD patients. We could correctly classify 49 out of 52 subjects in the category with/without tremor (97.96% sensitivity and 83.3% specificity) and 27 out of 32 patients in the category PD/ET (84.38% discrimination accuracy). Among TUD patients, 2 of 2 PD and 2 of 4 ET were correctly classified, and one patient having PD plus ET was classified as PD. Based on the analysis of smartphone accelerometer recordings, we found several kinematic features in the analysis of tremor that distinguished first between healthy subjects and patients and, ultimately, between PD and ET patients. The proposed method can give immediate results for the clinician to gain valuable information for the diagnosis of tremor. This can be useful in environments where more sophisticated diagnostic techniques are unavailable.

Emotion processing in Parkinson's disease: an EEG spectral power study.

PubMed

Yuvaraj, R; Murugappan, M; Omar, Mohd Iqbal; Ibrahim, Norlinah Mohamed; Sundaraj, Kenneth; Mohamad, Khairiyah; Satiyan, M

2014-07-01

Although an emotional deficit is a common finding in Parkinson's disease (PD), its neurobiological mechanism on emotion recognition is still unknown. This study examined the emotion processing deficits in PD patients using electroencephalogram (EEG) signals in response to multimodal stimuli. EEG signals were investigated on both positive and negative emotions in 14 PD patients and 14 aged-matched normal controls (NCs). The relative power (i.e., ratio of EEG signal power in each frequency band compared to the total EEG power) was computed over three brain regions: the anterior (AF3, F7, F3, F4, F8 and AF4), central (FC5 and FC6) and posterior (T7, P7, O1, O2, P8 and T8) regions for theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz) and gamma (30-60 Hz) frequency sub-bands, respectively. Behaviorally, PD patients showed decreased performance in classifying emotional stimuli as measured by subjective ratings. EEG power at theta, alpha, beta, and gamma bands in all regions were significantly different between the NC and PD groups during both the emotional tasks, with p-values less than 0.05. Furthermore, an increase of relative spectral powers in the theta and gamma bands and a decrease of relative powers in the alpha and beta bands were observed for PD patients compared with NCs during emotional information processing. The results suggest the possibility of the existence of a distinctive neurobiological substrate of PD patients during emotional information processing. Also, these distributed spectral powers in different frequency bands might provide meaningful information about emotional processing in PD patients.

Endoscopic approach to achalasia

PubMed Central

Müller, Michaela; Eckardt, Alexander J; Wehrmann, Till

2013-01-01

Achalasia is a primary esophageal motor disorder. The etiology is still unknown and therefore all treatment options are strictly palliative with the intention to weaken the lower esophageal sphincter (LES). Current established endoscopic therapeutic options include pneumatic dilation (PD) or botulinum toxin injection. Both treatment approaches have an excellent symptomatic short term effect, and lead to a reduction of LES pressure. However, the long term success of botulinum toxin (BT) injection is poor with symptom recurrence in more than 50% of the patients after 12 mo and in nearly 100% of the patients after 24 mo, which commonly requires repeat injections. In contrast, after a single PD 40%-60% of the patients remain asymptomatic for ≥ 10 years. Repeated on demand PD might become necessary and long term remission can be achieved with this approach in up to 90% of these patients. The main positive predictors for a symptomatic response to PD are an age > 40 years, a LES-pressure reduction to < 15 mmHg and/or an improved radiological esophageal clearance post-PD. However PD has a significant risk for esophageal perforation, which occurs in about 2%-3% of cases. In randomized, controlled studies BT injection was inferior to PD and surgical cardiomyotomy, whereas the efficacy of PD, in patients > 40 years, was nearly equivalent to surgery. A new promising technique might be peroral endoscopic myotomy, although long term results are needed and practicability as well as safety issues must be considered. Treatment with a temporary self expanding stent has been reported with favorable outcomes, but the data are all from one study group and must be confirmed by others before definite recommendations can be made. In addition to its use as a therapeutic tool, endoscopy also plays an important role in the diagnosis and surveillance of patients with achalasia. PMID:23951393

Effect of center practices on the choice of the first dialysis modality for children and young adults.

PubMed

Hogan, Julien; Ranchin, Bruno; Fila, Marc; Harambat, Jérome; Krid, Saoussen; Vrillon, Isabelle; Roussey, Gwenaelle; Fischbach, Michel; Couchoud, Cécile

2017-04-01

Peritoneal dialysis (PD) remains the modality of choice in children, but there is no clear evidence to support a better outcome in children treated with PD. We aimed to assess factors that have an impact on the choice of dialysis modality in children and young adults in France and sought to determine the roles of medical factors and center practices. We included all patients aged <20 years at the start of renal replacement therapy (RRT), recorded in the French RRT Registry between 2002 and 2013. Hierarchical logistic regression models were used to study the association between the patient/center characteristics and the probability of receiving PD as the first dialysis modality. We included 806 patients starting RRT in 177 centers, 23 of which were specialized pediatric centers. Six hundred and one patients (74.6 %) started with hemodialysis (HD), whereas 205 (25.4 %) started with PD. A greater probability of PD was found in younger children, whereas starting the treatment in an emergency setting was associated with a low use of PD. We found a significant variability among centers that accounted for 43 % of the total variability. The probability of PD was higher in adult centers and was proportional to the rate of PD in the center. Center practices are a major factor in the choice of dialysis modality. This raises concerns about patient and family choices and to what extent doctors may influence the final decision. Further pediatric studies focusing on children's and parents' wishes are needed to provide care as close as possible to patients' and families' expectations.

PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis.

PubMed

Hecht, Markus; Büttner-Herold, Maike; Erlenbach-Wünsch, Katharina; Haderlein, Marlen; Croner, Roland; Grützmann, Robert; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold V

2016-09-01

The influence of neoadjuvant radiochemotherapy (RCT) on programmed death-ligand 1 (PD-L1) expression, a predictive marker for programmed cell death protein 1 (PD-1) inhibitor therapy, was studied on tumour and inflammatory cells in rectal adenocarcinoma patients along with its prognostic value. PD-L1 immunohistochemistry was performed on tissue microarrays of 103 pre-RCT biopsies and 159 post-RCT surgical specimens (central tumour, invasive front and normal tissue) of 199 patients. In 63 patients, both samples were available. Proportion and maximum intensity of PD-L1-positive (PD-L1+) cells were evaluated. RCT increased the proportion of PD-L1-expressing cancer cells from 2.1% to 7.8% in the central tumour (p < 0.001) or 9.3% in the invasive front (p < 0.001). Cancer cell PD-L1 on its own could not predict prognosis. High PD-L1 expression on pre-RCT inflammatory cells (maximum intensity: p = 0.048) and post-RCT invasive front inflammatory cells (p = 0.010) correlated with improved no evidence of disease survival. In multivariate analysis, the combination of low PD-L1 in cancer and inflammatory cells was an independent negative prognostic marker for overall survival (OS) pre-RCT (Cox's proportional hazard ratio 0.438, p = 0.045) and in the invasive front post-RCT (Cox's proportional hazard ratio 0.257, p = 0.030). Neoadjuvant RCT is associated with an increased PD-L1 expression in rectal adenocarcinoma patients, which should prompt clinical trials combining radiotherapy and PD-1/PD-L1 pathway blockade. Combined low PD-L1 expression on tumour and inflammatory cells is an independent negative prognostic marker for OS in RCT of rectal adenocarcinoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuropsychological Characteristics and Their Association with Higher-Level Functional Capacity in Parkinson's Disease

PubMed Central

Miura, Kayoko; Matsui, Mie; Takashima, Shutaro; Tanaka, Kortaro

2015-01-01

Background/Aims Little is known about the relationship between cognitive functions and higher-level functional capacity (e.g. intellectual activity, social role, and social participation) in Parkinson's disease (PD). The purpose of this study was to clarify neuropsychological characteristics and their association with higher-level functional capacity in PD patients. Methods Participants were 31 PD patients and 23 demographically matched healthy controls. Neuropsychological tests were conducted. One year later, a questionnaire survey evaluated higher-level functional capacity in daily living. Results The PD group scored significantly lower than the control group in all cognitive domains, particularly executive function and processing. Executive function, processing speed, language, and memory were significantly correlated with higher-level functional capacity in PD patients. Stepwise regression showed that only executive function (Trail Making Test-B), together with disease severity (HY stage), predicted the higher-level functional capacity. Conclusion Our findings provide evidence of a relationship between executive function and higher-level functional capacity in patients with PD. PMID:26273243

SNCA 3'UTR genetic variants in patients with Parkinson's disease and REM sleep behavior disorder.

PubMed

Toffoli, M; Dreussi, E; Cecchin, E; Valente, M; Sanvilli, N; Montico, M; Gagno, S; Garziera, M; Polano, M; Savarese, M; Calandra-Buonaura, G; Placidi, F; Terzaghi, M; Toffoli, G; Gigli, G L

2017-07-01

REM sleep behavior disorder (RBD) is an early marker of Parkinson's disease (PD); however, it is still unclear which patients with RBD will eventually develop PD. Single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of alpha-synuclein (SNCA) have been associated with PD, but at present, no data is available about RBD. The 3'UTR hosts regulatory regions involved in gene expression control, such as microRNA binding sites. The aim of this study was to determine RBD specific genetic features associated to an increased risk of progression to PD, by sequencing of the SNCA-3'UTR in patients with "idiopathic" RBD (iRBD) and in patients with PD. We recruited 113 consecutive patients with a diagnosis of iRBD (56 patients) or PD (with or without RBD, 57 patients). Sequencing of SNCA-3'UTR was performed on genomic DNA extracted from peripheral blood samples. Bioinformatic analyses were carried out to predict the potential effect of the identified genetic variants on microRNA binding. We found three SNCA-3'UTR SNPs (rs356165, rs3857053, rs1045722) to be more frequent in PD patients than in iRBD patients (p = 0.014, 0.008, and 0.008, respectively). Four new or previously reported but not annotated specific genetic variants (KP876057, KP876056, NM_000345.3:c*860T>A, NM_000345.3:c*2320A>T) have been observed in the RBD population. The in silico approach highlighted that these variants could affect microRNA-mediated gene expression control. Our data show specific SNPs in the SNCA-3'UTR that may bear a risk for RBD to be associated with PD. Moreover, new genetic variants were identified in patients with iRBD.

Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease.

PubMed

Suppa, A; Marsili, L; Belvisi, D; Conte, A; Iezzi, E; Modugno, N; Fabbrini, G; Berardelli, A

2011-02-01

In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors "Group" and "Time". After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (p<0.01 at all time-points) but in PD patients with and without LIDs, on and off therapy, remained unchanged. In PD patients with and without LIDs, on and off therapy iTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features. Copyright © 2010 Elsevier Inc. All rights reserved.

Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

PubMed

Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

2017-12-01

Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

PD-1 (PDCD1) Promoter Methylation Is a Prognostic Factor in Patients With Diffuse Lower-Grade Gliomas Harboring Isocitrate Dehydrogenase (IDH) Mutations.

PubMed

Röver, Lea Kristin; Gevensleben, Heidrun; Dietrich, Jörn; Bootz, Friedrich; Landsberg, Jennifer; Goltz, Diane; Dietrich, Dimo

2018-02-01

Immune checkpoints are important targets for immunotherapies. However, knowledge on the epigenetic modification of immune checkpoint genes is sparse. In the present study, we investigated promoter methylation of CTLA4, PD-L1, PD-L2, and PD-1 in diffuse lower-grade gliomas (LGG) harboring isocitrate dehydrogenase (IDH) mutations with regard to mRNA expression levels, clinicopathological parameters, previously established methylation subtypes, immune cell infiltrates, and survival in a cohort of 419 patients with IDH-mutated LGG provided by The Cancer Genome Atlas. PD-L1, PD-L2, and CTLA-4 mRNA expression levels showed a significant inverse correlation with promoter methylation (PD-L1: p=0.005; PD-L2: p<0.001; CTLA-4: p<0.001). Furthermore, immune checkpoint methylation was significantly associated with age (PD-L2: p=0.003; PD-1: p=0.015), molecular alterations, i.e. MGMT methylation (PD-L1: p<0.001; PD-L2: p<0.001), ATRX mutations (PD-L2: p<0.001, PD-1: p=0.001), and TERT mutations (PD-L1: p=0.035, PD-L2: p<0.001, PD-1: p<0.001, CTLA4: p<0.001) as well as methylation subgroups and immune cell infiltrates. In multivariate Cox proportional hazard analysis, PD-1 methylation qualified as strong prognostic factor (HR=0.51 [0.34-0.76], p=0.001). Our findings suggest an epigenetic regulation of immune checkpoint genes via DNA methylation in LGG. PD-1 methylation may assist the identification of patients that might benefit from an alternative treatment, particularly in the context of emerging immunotherapies. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Altered Kinematics of Facial Emotion Expression and Emotion Recognition Deficits Are Unrelated in Parkinson's Disease.

PubMed

Bologna, Matteo; Berardelli, Isabella; Paparella, Giulia; Marsili, Luca; Ricciardi, Lucia; Fabbrini, Giovanni; Berardelli, Alfredo

2016-01-01

Altered emotional processing, including reduced emotion facial expression and defective emotion recognition, has been reported in patients with Parkinson's disease (PD). However, few studies have objectively investigated facial expression abnormalities in PD using neurophysiological techniques. It is not known whether altered facial expression and recognition in PD are related. To investigate possible deficits in facial emotion expression and emotion recognition and their relationship, if any, in patients with PD. Eighteen patients with PD and 16 healthy controls were enrolled in this study. Facial expressions of emotion were recorded using a 3D optoelectronic system and analyzed using the facial action coding system. Possible deficits in emotion recognition were assessed using the Ekman test. Participants were assessed in one experimental session. Possible relationship between the kinematic variables of facial emotion expression, the Ekman test scores, and clinical and demographic data in patients were evaluated using the Spearman's test and multiple regression analysis. The facial expression of all six basic emotions had slower velocity and lower amplitude in patients in comparison to healthy controls (all P s < 0.05). Patients also yielded worse Ekman global score and disgust, sadness, and fear sub-scores than healthy controls (all P s < 0.001). Altered facial expression kinematics and emotion recognition deficits were unrelated in patients (all P s > 0.05). Finally, no relationship emerged between kinematic variables of facial emotion expression, the Ekman test scores, and clinical and demographic data in patients (all P s > 0.05). The results in this study provide further evidence of altered emotional processing in PD. The lack of any correlation between altered facial emotion expression kinematics and emotion recognition deficits in patients suggests that these abnormalities are mediated by separate pathophysiological mechanisms.

Safety and Efficacy of PD-1 Inhibitors Among HIV-Positive Patients With Non-Small Cell Lung Cancer.

PubMed

Ostios-Garcia, Lorena; Faig, Jennifer; Leonardi, Giulia C; Adeni, Anika E; Subegdjo, Safiya J; Lydon, Christine A; Rangachari, Deepa; Huberman, Mark S; Sehgal, Kartik; Shea, Meghan; VanderLaan, Paul A; Cheng, Matthew P; Marty, Francisco M; Hammond, Sarah P; Costa, Daniel B; Awad, Mark M

2018-04-06

Despite widespread administration of programmed death receptor 1 (PD-1) pathway inhibitors among individuals with NSCLC, little is known about the safety and activity of these agents among human immunodeficiency virus (HIV) - infected patients since this population has largely been excluded from immunotherapy clinical trials. Here, we describe seven patients with metastatic NSCLC and HIV infection who were treated with PD-1 inhibitors nivolumab (two cases) or pembrolizumab (five cases with three in the first-line setting). Partial responses to immune checkpoint inhibitors were observed in three of seven cases. Among four patients with a programmed death ligand-1 tumor proportion score ≥50%, three partial responses were observed. All patients received antiretroviral therapy while on anti-PD-1 treatment. None of the patients experienced grade 3 or 4 immune-related adverse events or immune reconstitution inflammatory syndrome, and none required PD-1 inhibitor dose interruption or discontinuation due to toxicity. Nivolumab and pembrolizumab can be safe and effective among patients with NSCLC and HIV. Larger studies will be needed to determine the overall safety and efficacy of immune checkpoint inhibitors among cancer patients with HIV. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Espresso Coffee for the Treatment of Somnolence in Parkinson’s Disease: Results of n-of-1 Trials

PubMed Central

Ferreira, Joaquim J.; Mestre, Tiago; Guedes, Leonor Correia; Coelho, Miguel; Rosa, Mário M.; Santos, Ana T.; Barra, Márcio; Sampaio, Cristina; Rascol, Olivier

2016-01-01

There is limited information available concerning the treatment of daytime somnolence associated with Parkinson’s disease (PD); the most frequently applied therapeutic strategies include decreasing the dose of dopamine agonists or adding potential wake-promoting agents. There is recent data from a placebo-controlled trial concluding on a non-significant trend in favor of caffeine. We aimed to evaluate the efficacy of espresso-coffee in the treatment of daytime somnolence in PD. To evaluate the efficacy of espresso-coffee in the treatment of daytime somnolence in PD, we have conducted multiple single-patient (n-of-1) clinical trials comparing regular espresso coffee to decaffeinated coffee in PD patients presenting moderate to severe daytime somnolence defined as an Epworth Sleepiness Scale score >9. Each single-patient (n-of-1) trial included a sequence of three crossovers (two treatment periods separated by two days of washout). Four patients were included in the studies and three completed the three pairs of treatment periods. In two of the four patients, espresso coffee was considered beneficial. This study concludes that multiple single patient trials are feasible in PD and suggests that espresso-coffee may have a beneficial effect on daytime somnolence in some patients. These results cannot be generalized beyond the patients included in these trials. PMID:27014181

Effect of assistance on peritonitis risk in diabetic patients treated by peritoneal dialysis: report from the French Language Peritoneal Dialysis Registry.

PubMed

Benabed, Anais; Bechade, Clemence; Ficheux, Maxence; Verger, Christian; Lobbedez, Thierry

2016-04-01

Diabetic patients treated by peritoneal dialysis (PD) have been reported to be at an increased risk of peritonitis. This has been attributed to impairment in host defense, visual impairment, disability and muscle wasting, which could compromise ability to safely perform catheter connections. This study aimed to evaluate whether assisted PD is associated with a lower risk of peritonitis in diabetic patients. This was a retrospective study based on data from the French Language Peritoneal Dialysis Registry. We included diabetic patients starting PD between 1 January 2002 and 31 December 2012. The end of the observation period was 31 December 2013. Using complementary regression analysis (Fine and Gray, Hurdle models), we assessed the relationship between peritonitis occurrence, peritonitis number over time and the type of assisted PD. Of the 3598 diabetic patients, there were 2040 patients on nurse-assisted PD. These patients were older, more comorbid and more frequently on continuous ambulatory peritoneal dialysis (CAPD). In the multivariate analysis, nurse assistance was associated with a reduced risk of peritonitis in the Fine and Gray [subdistribution hazard ratio: 0.78 (95% confidence interval, CI, 0.68-0.89)] and in the first component of the Hurdle models [rate ratio: 0.82 (95% CI 0.71-0.93)], but not a lower incidence of peritonitis after an initial episode [rate ratio: 0.82 (95% CI 0.95-1.38)]. Transplant failure, glomerulonephritis and CAPD were associated with an increased risk. In France, nurse-assisted PD is associated with a lower risk of peritonitis in diabetic patients treated by PD but not a lower incidence of peritonitis. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Clinical Implications of Cardiac-MIBG SPECT in the Differentiation of Parkinsonian Syndromes

PubMed Central

Shin, Dong Hoon; Bang, Oh Young; Joo, In Soo; Huh, Kyoon

2006-01-01

Background and Purpose 123I cardiac meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used to estimate myocardial sympathetic nerve function. We investigate whether cardiac-MIBG SPECT is clinically applicable in the differentiation of Parkinson's disease (PD) from parkinsonian syndromes. Methods Cardiac-MIBG scintigraphy was performed in 27 controls, in 40 patients with PD and in 52 patients with other parkinsonian syndromes comprising 23 with multiple system atrophy (MSA), 26 with drug-induced parkinsonism (DIP), and 3 with corticobasal degeneration (CBD). The heart to mediastinum (H/M) uptake ratio was calculated for each subjects. Patients who either had medical conditions that confused the MIBG SPECT results or who took medications that interfere with MIBG accumulation were excluded from the study. Results Both early and delayed H/M ratios were in patients with PD significantly lower than in controls (early, 1.34±0.15 vs 1.79±0.19; delayed, 1.29±0.15 vs 2.06±0.29, p<0.001). In patients with PD, both early and delayed H/M ratios were significantly lower than those in patients with MSA (early, 1.68±0.23; delayed, 1.80±0.34, p<0.001), DIP (early, 1.83±0.24; delayed, 2.07±0.4, p<0.001), or CBD (early, 1.85±0.01; delayed, 1.99±0.19, p<0.001). Two patients with DIP, who were within the range of patients with PD, showed clinically similar courses of PD. Conclusions This study demonstrates that cardiac-MIBG is a clinically powerful tools to differentiate PD from other parkinsonian syndromes. PMID:20396485

Separating depressive comorbidity from panic disorder: A combined functional magnetic resonance imaging and machine learning approach.

PubMed

Lueken, Ulrike; Straube, Benjamin; Yang, Yunbo; Hahn, Tim; Beesdo-Baum, Katja; Wittchen, Hans-Ulrich; Konrad, Carsten; Ströhle, Andreas; Wittmann, André; Gerlach, Alexander L; Pfleiderer, Bettina; Arolt, Volker; Kircher, Tilo

2015-09-15

Depression is frequent in panic disorder (PD); yet, little is known about its influence on the neural substrates of PD. Difficulties in fear inhibition during safety signal processing have been reported as a pathophysiological feature of PD that is attenuated by depression. We investigated the impact of comorbid depression in PD with agoraphobia (AG) on the neural correlates of fear conditioning and the potential of machine learning to predict comorbidity status on the individual patient level based on neural characteristics. Fifty-nine PD/AG patients including 26 (44%) with a comorbid depressive disorder (PD/AG+DEP) underwent functional magnetic resonance imaging (fMRI). Comorbidity status was predicted using a random undersampling tree ensemble in a leave-one-out cross-validation framework. PD/AG-DEP patients showed altered neural activation during safety signal processing, while +DEP patients exhibited generally decreased dorsolateral prefrontal and insular activation. Comorbidity status was correctly predicted in 79% of patients (sensitivity: 73%; specificity: 85%) based on brain activation during fear conditioning (corrected for potential confounders: accuracy: 73%; sensitivity: 77%; specificity: 70%). No primary depressed patients were available; only medication-free patients were included. Major depression and dysthymia were collapsed (power considerations). Neurofunctional activation during safety signal processing differed between patients with or without comorbid depression, a finding which may explain heterogeneous results across previous studies. These findings demonstrate the relevance of comorbidity when investigating neurofunctional substrates of anxiety disorders. Predicting individual comorbidity status may translate neurofunctional data into clinically relevant information which might aid in planning individualized treatment. The study was registered with the ISRCTN80046034. Copyright © 2015 Elsevier B.V. All rights reserved.

Non-genetic factors associated with the risk of Parkinson’s disease in Iranian patients

PubMed Central

Hosseinitabatabaei, Narges; Babakhani, Babak; Hosseini-Tabatabaei, Azadeh; Vahabi, Zahra; Soltanzadeh, Akbar

2013-01-01

Summary The aim of this study was to investigate some of non-genetic factors associated with Parkinson’s disease (PD) in a sample of Iranian patients. This case-control study included 75 patients with idiopathic PD and 75 control patients. The patients in the control group were found to have drunk more glasses of tea per day than the case group before the onset of their problem (p=0.019). Every extra glass of tea per day decreased the risk of PD by 0.8 times (OR=0.8, 95%CI=0.73–0.97, p=0.02). Each cup of coffee per week decreased the chance of developing PD by 0.5 times (OR=0.5, 95%CI=0.28–0.9, p=0.021). A previous history of evening work increased PD risk by 4.6 times (OR=4.6, 95%CI=1.29–16.86, p=0.019) while major stressful events increased it by 13.5 times (OR=13.5, 95%CI=4.7–38.1, p=0.0001). In conclusion, coffee and tea consumption may exert a protective effect against PD, while evening work and stress may be risk factors for the development of the disease. PMID:24125560

Association of Serum Triglyceride Level and Gemfibrozil Consumption With Periodontal Status.

PubMed

Sayar, Ferena; Akhondi, Nasrin; Fallah, Soltanali; Moalemnia, Amir Abbas; Cheraghi, Azra

2017-05-01

Hyperlipidemia is a major risk factor for cardiovascular diseases. Considering the suggested association between periodontal and cardiovascular diseases, this study sought to assess the association, if any, between serum triglyceride (TG) levels and gemfibrozil consumption with periodontal parameters. This cross-sectional study was conducted on 90 participants, including 30 individuals with a normal lipid profile (group H), 30 patients with hypertriglyceridemia and not on medication (group N), and 30 patients with hypertriglyceridemia and taking gemfibrozil over a 3-month period (group M). Periodontal parameters including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index were measured at four sites of each tooth. Serum levels of total cholesterol (TC), TG, low-density lipoprotein, and high-density lipoprotein were measured. Mean values for PD and CAL in the two hypertriglyceridemic groups were significantly higher than those of the H group (P <0.001). After controlling for confounding variables, significant linear correlations were noted between PD and BOP, PD and TC, PD and TG, and CAL and TG in each group (P <0.01). Patients with hypertriglyceridemia had worse periodontal status than healthy controls. Patients with hypertriglyceridemia who were taking gemfibrozil did not show significant differences in CAL and PD compared with untreated patients with hypertriglyceridemia.

Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

PubMed Central

Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

2015-01-01

Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L1 MAb would potentially be able to block PD-L1/PD1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 MAb. The studies reported here demonstrate (a) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (b) IFNγ can enhance tumor cell PD-L1 expression and in some cases enhance ADCC tumor cell lysis; (c) purified NK cells are potent effectors for avelumab; (d) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (e) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (f) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 MAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. PMID:26014098

Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells.

PubMed

Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R; Gulley, James L; Tsang, Kwong Yok; Schlom, Jeffrey

2015-10-01

Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 mAb. The studies reported here demonstrate (i) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (ii) IFNγ can enhance tumor cell PD-L1 expression and, in some cases, enhance ADCC tumor cell lysis; (iii) purified NK cells are potent effectors for avelumab; (iv) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (v) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (vi) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 mAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. ©2015 American Association for Cancer Research.

Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer

PubMed Central

Bastman, Jill J.; Serracino, Hilary S.; Zhu, Yuwen; Koenig, Michelle R.; Mateescu, Valerica; Sams, Sharon B.; Davies, Kurtis D.; Raeburn, Christopher D.; McIntyre, Robert C.; Haugen, Bryan R.

2016-01-01

Context: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3–5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases. Objective: We hypothesized that a T-cell response is generated in advanced thyroid cancer and may be a viable therapeutic target. Design: Primary DTCs were analyzed by quantitative RT-PCR (n = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1, PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were analyzed by immunohistochemistry. Setting: The study was conducted at the University of Colorado Hospital. Patients: Thyroid cancer patients undergoing thyroidectomy or completion surgery for advanced disease between 2002 and 2013 participated in the study. Intervention: There were no interventions. Main Outcome Measure: Immune markers were analyzed for association with disease severity. Results: Immune markers were commonly expressed at the RNA level. PD-L1 was higher (P = .0443) in patients with nodal metastases. FoxP3+ (P < .0001), PD-1+CD8+ (P = .0058), and PD-1+CD4+ (P = .0104) T cells were enriched in DTC biopsies. CD8+ and FoxP3+ T cells were detected by immunohistochemistry in all pT4 tumors and a subset of metastases. PD-1+ lymphocytes were found in 50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22 cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373). BRAFV600E mutation was associated with higher frequencies of tumor-associated lymphocytes (P = .0095) but not PD-L1 expression. Conclusions: PD-1 checkpoint blockades may have therapeutic efficacy in patients with aggressive forms of thyroid cancer. PMID:27045886

Peritoneal dialysis in rural Australia.

PubMed

Gray, Nicholas A; Grace, Blair S; McDonald, Stephen P

2013-12-20

Australians living in rural areas have lower incidence rates of renal replacement therapy and poorer dialysis survival compared with urban dwellers. This study compares peritoneal dialysis (PD) patient characteristics and outcomes in rural and urban Australia. Non-indigenous Australian adults who commenced chronic dialysis between 1 January 2000 and 31 December 2010 according to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) were investigated. Each patient's residence was classified according to the Australian Bureau of Statistics remote area index as major city (MC), inner regional (IR), outer regional (OR), or remote/very remote (REM). A total of 7657 patients underwent PD treatment during the study period. Patient distribution was 69.0% MC, 19.6% IR, 9.5% OR, and 1.8% REM. PD uptake increased with increasing remoteness. Compared with MC, sub-hazard ratios [95% confidence intervals] for commencing PD were 1.70 [1.61-1.79] IR, 2.01 [1.87-2.16] OR, and 2.60 [2.21-3.06] REM. During the first 6 months of PD, technique failure was less likely outside MC (sub-hazard ratio 0.47 [95% CI: 0.35-0.62], P < 0.001), but no difference was seen after 6 months (sub-hazard ratio 1.05 [95% CI: 0.84-1.32], P = 0.6). Technique failure due to technical (sub-hazard ratio 0.57 [95% CI: 0.38-0.84], P = 0.005) and non-medical causes (sub-hazard ratio 0.52 [95% CI: 0.31-0.87], P = 0.01) was less likely outside MC. Time to first peritonitis episode was not associated with remoteness (P = 0.8). Patient survival while on PD or within 90 days of stopping PD did not differ by region (P = 0.2). PD uptake increases with increasing remoteness. In rural areas, PD technique failure is less likely during the first 6 months and time to first peritonitis is comparable to urban areas. Mortality while on PD does not differ by region. PD is therefore a good dialysis modality choice for rural patients in Australia.

Health service costs and clinical gains of psychotherapy for personality disorders: a randomized controlled trial of day-hospital-based step-down treatment versus outpatient treatment at a specialist practice

PubMed Central

2013-01-01

Background Day-hospital-based treatment programmes have been recommended for poorly functioning patients with personality disorders (PD). However, more research is needed to confirm the cost-effectiveness of such extensive programmes over other, presumably simpler, treatment formats. Methods This study compared health service costs and psychosocial functioning for PD patients randomly allocated to either a day-hospital-based treatment programme combining individual and group psychotherapy in a step-down format, or outpatient individual psychotherapy at a specialist practice. It included 107 PD patients, 46% of whom had borderline PD, and 40% of whom had avoidant PD. Costs included the two treatment conditions and additional primary and secondary in- and outpatient services. Psychosocial functioning was assessed using measures of global (observer-rated GAF) and occupational (self-report) functioning. Repeated assessments over three years were analysed using mixed models. Results The costs of step-down treatment were higher than those of outpatient treatment, but these high costs were compensated by considerably lower costs of other health services. However, costs and clinical gains depended on the type of PD. For borderline PD patients, cost-effectiveness did not differ by treatment condition. Health service costs declined during the trial, and functioning improved to mild impairment levels (GAF > 60). For avoidant PD patients, considerable adjuvant health services expanded the outpatient format. Clinical improvements were nevertheless superior to the step-down condition. Conclusion Our results indicate that decisions on treatment format should differentiate between PD types. For borderline PD patients, the costs and gains of step-down and outpatient treatment conditions did not differ. For avoidant PD patients, the outpatient format was a better alternative, leaning, however, on costly additional health services in the early phase of treatment. Trial registration Clinical Trials NCT00378248 PMID:24268099

Cortisol stress response in post-traumatic stress disorder, panic disorder, and major depressive disorder patients.

PubMed

Wichmann, Susann; Kirschbaum, Clemens; Böhme, Carsten; Petrowski, Katja

2017-09-01

Previous research has focussed extensively on the distinction of HPA-axis functioning between patient groups and healthy volunteers, with relatively little emphasis on a direct comparison of patient groups. The current study's aim was to analyse differences in the cortisol stress response as a function of primary diagnosis of panic disorder (PD), post-traumatic stress disorder (PTSD), and major depressive disorder (MDD). A total of n=30 PD (mean age±SD: 36.07±12.56), n=23 PTSD (41.22±10.17), n=18 MDD patients (39.00±14.93) and n=47 healthy control (HC) individuals (35.51±13.15) participated in this study. All the study participants were female. The Trier Social Stress Test (TSST) was used for reliable laboratory stress induction. Blood sampling accompanied the TSST for cortisol and ACTH assessment. Panic-related, PTSD-specific questionnaires and the Beck Depression Inventory II were handed out for the characterisation of the study groups. Repeated measure ANCOVAs were conducted to test for main effects of time or group and for interaction effects. Regression analyses were conducted to take comorbid depression into account. 26.7% of the PD patients, 43.5% of the PTSD patients, 72.2% of the MDD patients and 80.6% of the HC participants showed a cortisol stress response upon the TSST. ANCOVA revealed a cortisol hypo-responsiveness both in PD and PTSD patients, while no significant group differences were seen in the ACTH concentrations. Additional analyses showed no impact of comorbid depressiveness on the cortisol stress response. MDD patients did not differ in the hormonal stress response neither compared to the HC participants nor to the PD and PTSD patients. Our main findings provide evidence of a dissociation between the cortisol and ACTH concentrations in response to the TSST in PTSD and in PD patients, independent of comorbid depression. Our results further support overall research findings of a cortisol hypo-responsiveness in PD patients. A hypo-response pattern was also seen in the PTSD patients agreeing with previous finding on the cortisol stress reactivity following TSST stress induction in these patients. Patients with a primary MDD diagnosis showed descriptively higher cortisol concentrations compared to the anxiety patients, and lower cortisol concentrations as the healthy individuals. The limitations of the study and implications for future studies will be discussed. Copyright © 2017. Published by Elsevier Ltd.

Finger tapping analysis in patients with Parkinson's disease and atypical parkinsonism.

PubMed

Djurić-Jovičić, Milica; Petrović, Igor; Ječmenica-Lukić, Milica; Radovanović, Saša; Dragašević-Mišković, Nataša; Belić, Minja; Miler-Jerković, Vera; Popović, Mirjana B; Kostić, Vladimir S

2016-08-01

The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinson's disease (PD), progressive supranuclear palsy-Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n=13), PSP-R (n=15), and MSA-P (n=14) patients and matched healthy controls (HC; n=14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of -0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (-0.21°/cycle, p=0.032), and particularly from PD (-0.56°/cycle, p=0.001), and MSA-P patients (-1.48°/cycle, p=0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (pmsa-pd=0.726, pmsa-psp=0.363, ppsp-pd=0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency

PubMed Central

Lee, Jaewoong; Choi, Hayoung; Kim, Jiyeon; Kwon, Ahlm; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Lee, Jae Wook; Chung, Nack-Gyun

2017-01-01

Background We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. Methods In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. Results One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. Conclusions The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability. PMID:28028996

Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency.

PubMed

Lee, Jaewoong; Park, Joonhong; Choi, Hayoung; Kim, Jiyeon; Kwon, Ahlm; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Lee, Jae Wook; Chung, Nack Gyun; Cho, Bin

2017-03-01

We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability.

The effects of anxiety and external attentional focus on postural control in patients with Parkinson's disease

PubMed Central

Jazaeri, Seyede Zohreh; Azad, Akram; Mehdizadeh, Hajar; Habibi, Seyed Amirhassan; Mandehgary Najafabadi, Mahbubeh; Saberi, Zakieh Sadat; Rahimzadegan, Hawre; Moradi, Saeed; Behzadipour, Saeed; Parnianpour, Mohamad; Khalaf, Kinda

2018-01-01

Background Although anxiety is a common non-motor outcome of Parkinson's disease (PD) affecting 40% of patients, little attention has been paid so far to its effects on balance impairment and postural control. Improvement of postural control through focusing on the environment (i.e. external focus) has been reported, but the role of anxiety, as a confounding variable, remains unclear. Objectives This study aimed to investigate the influence of anxiety and attentional focus instruction on the standing postural control of PD patients. Methods Thirty-four patients with PD (17 with high anxiety (HA-PD) and 17 with low anxiety (LA-PD)), as well as 17 gender- and age-matched healthy control subjects (HC) participated in the study. Postural control was evaluated using a combination of two levels of postural difficulty (standing on a rigid force plate surface with open eyes (RO) and standing on a foam surface with open eyes (FO)), as well as three attentional focus instructions (internal, external and no focus). Results Only the HA-PD group demonstrated significant postural control impairment as compared to the control, as indicated by significantly greater postural sway measures. Moreover, external focus significantly reduced postural sway in all participants especially during the FO condition. Conclusion The results of the current study provide evidence that anxiety influences balance control and postural stability in patients with PD, particularly those with high levels of anxiety. The results also confirmed that external focus is a potential strategy that significantly improves the postural control of these patients. Further investigation of clinical applicability is warranted towards developing effective therapeutic and rehabilitative treatment plans. PMID:29390029

Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease.

PubMed

Iacovelli, Elisa; Gilio, Francesca; Meco, Giuseppe; Fattapposta, Francesco; Vanacore, Nicola; Brusa, Livia; Giacomelli, Elena; Gabriele, Maria; Rubino, Alfonso; Locuratolo, Nicoletta; Iani, Cesare; Pichiorri, Floriana; Colosimo, Carlo; Carbone, Antonio; Palleschi, Giovanni; Inghilleri, Maurizio

2010-07-15

In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.

Frequency of G6PD Mediterranean in individuals with and without malaria in Southern Pakistan.

PubMed

Moiz, Bushra; Arshad, Haroon Muhammad; Raheem, Ahmed; Hayat, Hasan; Karim Ghanchi, Najia; Beg, M Asim

2017-10-24

Pakistan has an estimated annual burden of 1.5 million malaria cases. The current situation calls for an effective malaria control and eradication programme in this country. Currently, primaquine is an attractive option for eliminating reservoirs of Plasmodium vivax hypnozoites and killing gametocytes of Plasmodium falciparum. However, this drug causes haemolysis in individuals who are glucose-6-phosphate (G6PD) deficient. It is important to map G6PD deficiency and malaria distribution in Pakistan to design an effective malaria eradication regimen. Frequency of G6PD deficiency (G6PDd) in malaria patients has not been reported from Pakistan in any meaningful way. The purpose of this study was to evaluate the frequency of G6PD c.563C>T (G6PD Mediterranean) in male individuals with and without falciparum malaria. Two hundred and ten archived DNA samples from males (110 from falciparum malaria patients and 100 from healthy individuals) were utilized in this study. Healthy blood donors were selected based on stringent pre-defined criteria. Patients were confirmed for malaria parasites on microscopy and or immune chromatographic assay detecting P. falciparum histidine-rich protein 2. Parasitaemia was also computed. DNA samples were tested for G6PD c.563C>T mutation through PCR-RFLP according to the previously defined protocol and its allelic frequency was computed. G6PD c.563C>T was observed in four of 110 patients with falciparum malaria and in two of 100 healthy donors. Mean (± SD) haemoglobin, median (IQR) platelet and median (IQR) parasite count in G6PD-deficient malaria-patients were 8.9 ± 0.9 g/dL, 124 × 109/L (IQR 32, 171) and 57,920/μL of blood (IQR 12,920, 540,000) respectively. Cumulative allelic frequency for G6PD 563c.C>T was 0.0285 detected in 6 of 210 X-chromosomes in Southern Pakistan. Frequency for this G6PD allele was 0.0364 in malaria-patients and 0.0200 in healthy individuals. Large studies including females are needed to elucidate the true burden of G6PDd in malaria-endemic areas. The information will enable local health policy makers to design effective strategies for eliminating malaria form this region.

SNP rs356219 of the α-synuclein (SNCA) gene is associated with Parkinson's disease in a Chinese Han population.

PubMed

Pan, Fenghua; Dong, Hairong; Ding, Haixia; Ye, Min; Liu, Weiguo; Wu, Yanfeng; Zhang, Xueling; Chen, Zhuoyou; Luo, Yang; Ding, Xinsheng

2012-06-01

Over the last decades, increasing knowledge about the genetic architecture of Parkinson's disease(PD) has provided novel insights into the pathogenesis of the disorder. Recently, several studies in different populations have found a strong association between idiopathic PD and the single-nucleotide polymorphism (SNP) rs356219, which is located in the 3'UTR of the SNCA gene. In this study, we aimed to verify these findings and to explore further the nature of the association in a subset of Chinese Han PD patients. Four hundred and three unrelated patients with sporadic PD and 315 healthy ethnically matched control subjects were recruited consecutively for the study. Patients and normal controls were genotyped for SNCA rs356219 variant by ligase detection reaction (LDR). A statistically significant difference was found in the frequencies of the single alleles of rs356219 (χ(2) = 12.986,P = 0.002) between PD patients and normal subjects. The distribution of A > G genotypes was different between patients and controls (χ(2) = 13.243, P < 0.001). The OR for subjects with the variant genotypes (AG and GG) was 1.88 (95%CI = 1.27-2.78, P = 0.001). The frequencies of the homozygous genotype for this variant was 42.2% (170 patients), which was significantly higher than that in controls (32.4%, P < 0.001). The results suggested that SNCA rs356219 variant might have an increased risk of susceptibility to PD in a Chinese Han population. Further studies are needed to replicate the association that we found. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reward and loss anticipation in panic disorder: An fMRI study.

PubMed

Held-Poschardt, Dada; Sterzer, Philipp; Schlagenhauf, Florian; Pehrs, Corinna; Wittmann, Andre; Stoy, Meline; Hägele, Claudia; Knutson, Brian; Heinz, Andreas; Ströhle, Andreas

2018-01-30

Anticipatory anxiety and harm avoidance are essential features of panic disorder (PD) and may involve deficits in the reward system of the brain, in particular in the ventral striatum. While neuroimaging studies on PD have focused on fearful and negative affective stimulus processing, no investigations have directly addressed deficits in reward and loss anticipation. To determine whether the ventral striatum shows abnormal neural activity in PD patients during anticipation of loss or gain, an event-related functional magnetic resonance imaging experiment using a monetary incentive delay task was employed in 10 patients with PD and 10 healthy controls. A repeated-measures ANOVA to identify effects of group (PD vs. Control) and condition (anticipation of loss vs. gain vs. neutral outcome) revealed that patients with PD showed significantly reduced bilateral ventral striatal activation during reward anticipation but increased activity during loss anticipation. Within the patient group, the degree of activation in the ventral striatum during loss-anticipation was positively correlated with harm avoidance and negatively correlated with novelty seeking. These findings suggest that behavioural impairments in panic disorder may be related to abnormal neural processing of motivational cues. Copyright © 2017 Elsevier B.V. All rights reserved.

A neurocomputational account of cognitive deficits in Parkinson’s disease

PubMed Central

Hélie, Sébastien; Paul, Erick J.; Ashby, F. Gregory

2014-01-01

Parkinson’s disease (PD) is caused by the accelerated death of dopamine (DA) producing neurons. Numerous studies documenting cognitive deficits of PD patients have revealed impairments in a variety of tasks related to memory, learning, visuospatial skills, and attention. While there have been several studies documenting cognitive deficits of PD patients, very few computational models have been proposed. In this article, we use the COVIS model of category learning to simulate DA depletion and show that the model suffers from cognitive symptoms similar to those of human participants affected by PD. Specifically, DA depletion in COVIS produced deficits in rule-based categorization, non-linear information-integration categorization, probabilistic classification, rule maintenance, and rule switching. These were observed by simulating results from younger controls, older controls, PD patients, and severe PD patients in five well-known tasks. Differential performance among the different age groups and clinical populations was modeled simply by changing the amount of DA available in the model. This suggests that COVIS may not only be an adequate model of the simulated tasks and phenomena but also more generally of the role of DA in these tasks and phenomena. PMID:22683450

Screening for residual disease in pediatric burkitt lymphoma using consensus primer pools.

PubMed

Agsalda, Melissa; Kusao, Ian; Troelstrup, David; Shiramizu, Bruce

2009-01-01

Assessing molecular persistent or minimal residual disease (PD/MRD) in childhood Burkitt lymphoma (BL) is challenging because access to original tumor is usually needed to design patient-specific primers (PSPs). Because BL is characterized by rearranged immunoglobulin heavy chain (IgV(H)) genes, IgV(H) primer pools from IgV(H1)-IgV(H7) regions were tested to detect PD/MRD, thus eliminating the need for original tumor. The focus of the current study was to assess the feasibility of using IgV(H) primer pools to detect disease in clinical specimens. Fourteen children diagnosed with B-NHL had follow-up repository specimens available to assess PD/MRD. Of the 14 patients, 12 were PD/MRD negative after 2 months of therapy and remained in remission at the end of therapy; 2/14 patients were PD/MRD positive at 2-3 months and later relapsed. PSP-based assays from these 14 patients showed 100% concordance with the current assay. This feasibility study warrants further investigation to assess PD/MRD using IgV(H) primer pools, which could have clinical significance as a real-time assessment tool to monitor pediatric BL and possibly other B-cell non-Hodgkin lymphoma therapy.

Role of interleukin-6 and pentraxin 3 as an early marker in Peyronie's disease.

PubMed

Atar, Arda; Kural, Alev; Yenice, Gurkan; Comez, Ilker; Tugcu, Volkan

2017-04-01

Inflammation is mechanistically involved in the development of Peyronie's disease (PD). The aim of this study is to assess the relevance of serum pentraxin 3 (PTX3) and interleukin-6 (IL-6) concentrations in PD. The study enrolled 40 patients with PD in the acute phase and 40 healthy controls. Plasma PTX3 and IL-6 concentrations were evaluated in 40 patients in the acute phase of PD and 40 healthy controls by enzyme-linked immunosorbent assay. Serum concentrations of both PTX3 and IL-6 were significantly higher in the PD patients than in the control group (p=0.001 and p=0.001, respectively). There was a significant correlation between concentration of PTX3 and painful erections. IL-6 concentrations were significantly higher in patients with erectile dysfunction. IL-6 and PTX3 levels showed no correlation with age, serum C-reactive protein, degree of curvature, and disease duration. IL-6 trans-signaling and PTX3 amplification at the site of inflammation could have a role in pathophysiological mechanisms of PD. Biological drugs may be used for treatment during the acute phase of the disease based on this mechanism. Copyright © 2017. Published by Elsevier Taiwan.

Biometric Digital Health Technology for Measuring Motor Function in Parkinson's Disease: Results from a Feasibility and Patient Satisfaction Study.

PubMed

Mitsi, Georgia; Mendoza, Enrique Urrea; Wissel, Benjamin D; Barbopoulou, Elena; Dwivedi, Alok K; Tsoulos, Ioannis; Stavrakoudis, Athanassios; Espay, Alberto J; Papapetropoulos, Spyros

2017-01-01

To assess the feasibility, predictive value, and user satisfaction of objectively quantifying motor function in Parkinson's disease (PD) through a tablet-based application (iMotor) using self-administered tests. PD and healthy controls (HCs) performed finger tapping, hand pronation-supination and reaction time tasks using the iMotor application. Thirty-eight participants (19 with PD and 17 HCs) were recruited in the study. PD subjects were 53% male, with a mean age of 67.8 years (±8.8), mean disease duration of 6.5 years (±4.6), Movement Disorders Society version of the Unified Parkinson Disease Rating Scale III score 26.3 (±6.7), and Hoehn & Yahr stage 2. In the univariate analysis, most tapping variables were significantly different in PD compared to HC. Tap interval provided the highest predictive ability (90%). In the multivariable logistic regression model reaction time (reaction time test) ( p  = 0.021) and total taps (two-target test) ( p  = 0.026) were associated with PD. A combined model with two-target (total taps and accuracy) and reaction time produced maximum discriminatory performance between HC and PD. The overall accuracy of the combined model was 0.98 (95% confidence interval: 0.93-1). iMotor use achieved high rates of patients' satisfaction as evaluated by a patient satisfaction survey. iMotor differentiated PD subjects from HCs using simple alternating tasks of motor function. Results of this feasibility study should be replicated in larger, longitudinal, appropriately designed, controlled studies. The impact on patient care of at-home iMotor-assisted remote monitoring also deserves further evaluation.

Caregivers' and physicians' attitudes to rotigotine transdermal patch versus oral Parkinson's disease medication: an observational study.

PubMed

Sieb, Jörn Peter; Themann, Peter; Warnecke, Tobias; Lauterbach, Thomas; Berkels, Reinhard; Grieger, Frank; Lorenzl, Stefan

2015-05-01

To provide real-world data on caregiver and physician perceptions of the advantages and disadvantages of rotigotine transdermal patch (Neupro * ) versus oral Parkinson's Disease (PD) medication. Cross-sectional, non-interventional study in routine clinical practice in Germany (NCT01330290). Patients had PD with documented need for care, and had received rotigotine transdermal patch as add-on to oral PD treatment for ≥1 month. Caregivers/nurses and physicians assessed rotigotine transdermal patch versus oral PD medications using questionnaires. Specific questions regarding the possible benefits of transdermal application were asked and comprised questions on: swallowing dysfunction, nausea/vomiting, monitoring therapy, once daily application, application independently from meals, application to sleeping patients, caregiving efforts (caregivers only) and clinical aspects (physicians only). Each question was assessed on a 5 point scale ranging from -2 (major disadvantage) to 2 (major advantage) compared with oral treatment. Primary outcomes were mean total scores of all questions for caregivers/nurses and physicians who provided responses for ≥4 questions. As there are no validated tools to assess physician/caregiver preference in the PD setting, there is no reference against which the current findings can be compared; this study serves to pilot the questionnaires. Questionnaire responses from 128 caregivers/nurses and 41 physicians were documented for 147 patients. One hundred (68%) patients had a caregiving family member; 40 (27%) were cared for by a nurse. Mean PD duration was 8.2 (SD 6.3) years; 136 (93%) patients were taking levodopa. Mean total score of caregivers'/nurses' questionnaires was 1.32 (SD 0.67) and of physicians' questionnaires was 1.46 (0.32) indicating a perceived advantage of rotigotine transdermal patch over oral PD therapy. Mean scores for individual questions were in the range 1.03-1.54 for caregivers/nurses and 1.15-1.87 for physicians. When given a choice about rationale to prescribe, physicians cited pharmaceutical form (patch) in 139 (95%) cases and active agent (rotigotine) in 89 (61%) cases. Caregivers/nurses and physicians perceived advantages with rotigotine transdermal patch compared to an oral PD medication as add-on therapy in patients with PD; advantages were observed in aspects of medical treatment as well as in everyday situations of caregiving of PD patients.

PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?

PubMed Central

Xu-Monette, Zijun Y.; Zhang, Mingzhi; Li, Jianyong; Young, Ken H.

2017-01-01

PD-1–PD-L1 interaction is known to drive T cell dysfunction, which can be blocked by anti-PD-1/PD-L1 antibodies. However, studies have also shown that the function of the PD-1–PD-L1 axis is affected by the complex immunologic regulation network, and some CD8+ T cells can enter an irreversible dysfunctional state that cannot be rescued by PD-1/PD-L1 blockade. In most advanced cancers, except Hodgkin lymphoma (which has high PD-L1/L2 expression) and melanoma (which has high tumor mutational burden), the objective response rate with anti-PD-1/PD-L1 monotherapy is only ~20%, and immune-related toxicities and hyperprogression can occur in a small subset of patients during PD-1/PD-L1 blockade therapy. The lack of efficacy in up to 80% of patients was not necessarily associated with negative PD-1 and PD-L1 expression, suggesting that the roles of PD-1/PD-L1 in immune suppression and the mechanisms of action of antibodies remain to be better defined. In addition, important immune regulatory mechanisms within or outside of the PD-1/PD-L1 network need to be discovered and targeted to increase the response rate and to reduce the toxicities of immune checkpoint blockade therapies. This paper reviews the major functional and clinical studies of PD-1/PD-L1, including those with discrepancies in the pathologic and biomarker role of PD-1 and PD-L1 and the effectiveness of PD-1/PD-L1 blockade. The goal is to improve understanding of the efficacy of PD-1/PD-L1 blockade immunotherapy, as well as enhance the development of therapeutic strategies to overcome the resistance mechanisms and unleash the antitumor immune response to combat cancer. PMID:29255458

PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?

PubMed

Xu-Monette, Zijun Y; Zhang, Mingzhi; Li, Jianyong; Young, Ken H

2017-01-01

PD-1-PD-L1 interaction is known to drive T cell dysfunction, which can be blocked by anti-PD-1/PD-L1 antibodies. However, studies have also shown that the function of the PD-1-PD-L1 axis is affected by the complex immunologic regulation network, and some CD8 + T cells can enter an irreversible dysfunctional state that cannot be rescued by PD-1/PD-L1 blockade. In most advanced cancers, except Hodgkin lymphoma (which has high PD-L1/L2 expression) and melanoma (which has high tumor mutational burden), the objective response rate with anti-PD-1/PD-L1 monotherapy is only ~20%, and immune-related toxicities and hyperprogression can occur in a small subset of patients during PD-1/PD-L1 blockade therapy. The lack of efficacy in up to 80% of patients was not necessarily associated with negative PD-1 and PD-L1 expression, suggesting that the roles of PD-1/PD-L1 in immune suppression and the mechanisms of action of antibodies remain to be better defined. In addition, important immune regulatory mechanisms within or outside of the PD-1/PD-L1 network need to be discovered and targeted to increase the response rate and to reduce the toxicities of immune checkpoint blockade therapies. This paper reviews the major functional and clinical studies of PD-1/PD-L1, including those with discrepancies in the pathologic and biomarker role of PD-1 and PD-L1 and the effectiveness of PD-1/PD-L1 blockade. The goal is to improve understanding of the efficacy of PD-1/PD-L1 blockade immunotherapy, as well as enhance the development of therapeutic strategies to overcome the resistance mechanisms and unleash the antitumor immune response to combat cancer.

Increased Risk of Dementia in Patients With Chronic Obstructive Pulmonary Disease

PubMed Central

Liao, Kuang-Ming; Ho, Chung-Han; Ko, Shian-Chin; Li, Chung-Yi

2015-01-01

Abstract Neurodegenerative disease in patients with chronic obstructive pulmonary disease (COPD) was observed. We aim to clarify the risk of dementia in patients with COPD. The study used claims data from Taiwan's National Health Insurance Research Database. Subjects were those who received a discharge diagnosis of COPD between January 1, 2002 and December 31, 2011. Only the first hospitalization was enrolled, and the index date was the first day of admission. Patients younger than 40 years or those with a history of Alzheimer disease (AD) or Parkinson disease (PD) before the index date were excluded. The patients with COPD were then followed until receiving a diagnosis of AD or PD, death, or the end of the study. Control subjects were selected from hospitalized patients without a history of COPD, AD, or PD and were matched according to age (±3 years), gender, and the year of admission at a 2:1 ratio. The comorbidities were measured from 1 year before the index date based on the ICD-9-CM codes. The study included 8640 patients with COPD and a mean age of 68.76 (±10.74) years. The adjusted hazard ratio of developing dementia (AD or PD) was 1.74 (95% confidence interval = 1.55–1.96) in patients with COPD compared with patients without COPD after adjusting for age, gender, and comorbidities. This nationwide cohort study demonstrates that the risk of dementia, including AD and PD, is significantly increased in patients with COPD compared with individuals in the general population. PMID:26061317

Long-term results of pneumatic dilatation for relapsing symptoms of achalasia after Heller myotomy.

PubMed

Legros, Ludivine; Ropert, Alain; Brochard, Charlène; Bouguen, Guillaume; Pagenault, Maël; Siproudhis, Laurent; Bretagne, Jean-François

2014-09-01

The aim of this study was to assess the efficacy and safety of pneumatic dilatation (PD) to treat symptom recurrence after Heller myotomy (HM). Consecutive patients receiving PD for relapsing symptoms following prior HM were included in this retrospective single-center study. Eckardt score ≤3 and/or ∆ Eckardt (difference between Eckardt score before and after dilatation) ≥3 defined the success of initial dilatation. Patients who maintained response longer than 2 months after initial dilatation were defined as short-term responders. Relapsers were offered further on-demand dilatation. Remission was defined as an Eckardt score ≤3 at the study endpoint. Kaplan-Meier survival curves were used to determine relapse rates. Eighteen patients (11 women, seven men) were included from January 2004 to January 2013. Ten patients had type I achalasia, and seven had type III, according to the Chicago classification. Thirty-nine PDs were performed (1.5 [1-2.25] per patient). All patients had short-term responses. The remission rate at the endpoint, after a median follow-up of 33 months, was 78%, but 44% were treated with on-demand PD during the follow-up interval. The proportions of patients without relapse and subsequent PD were 72% at 12 months, 65% at 24 and 36 months, and 49% at 48 months. No factors predictive of long-term response, particularly the type of achalasia, could be identified in this series. There were no perforations. In treating symptom recurrence following HM, PD was safe and effective over the long term when combined with subsequent PD. © 2014 John Wiley & Sons Ltd.

Gait Monitoring for Early Neurological Disorder Detection Using Sensors in a Smartphone: Validation and a Case Study of Parkinsonism.

PubMed

Raknim, Paweeya; Lan, Kun-Chan

2016-01-01

Diagnosing brain disorders, such as Parkinson's disease (PD) or Alzheimer's disease, is often difficult, especially in the early stages. Moreover, it has been estimated that nearly 40% of people with PD may not be diagnosed. Traditionally, the diagnosis of neurological disorders, such as PD, often required a doctor to observe the patient over time to recognize signs of rigidity in movement. The pedestrian dead reckoning (PDR) system is a self-contained technique that has been widely used for indoor localization. In this work we propose a PDR-based method to continuously monitor and record the patient's gait characteristics using a smartphone. Seventeen patients were studied over a period of 1 year. During the year it became apparent that 1 of the patients was actually developing PD. To the best of our knowledge, our work is the first attempt to use sensors in a smartphone to help identify patients in their early stages of neurological disease. On average, the accuracy of our step length estimation was about 98%. Using a binary classification method-namely, support vector machine-we carried out a case study and showed that it was feasible to identify changes in the walking patterns of a PD patient with an accuracy of 94%. Using 1 year of gait trace data obtained from the users' phones, our work provides a first step to experimentally show the possibility of applying smartphone sensor data to provide early warnings to potential PD patients to encourage them to seek medical assistance and thus help doctors diagnose this disease earlier.

Deep Brain Stimulation of Pedunculopontine Nucleus for Postural Instability and Gait Disorder After Parkinson Disease: A Meta-Analysis of Individual Patient Data.

PubMed

Wang, Jia-Wei; Zhang, Yu-Qing; Zhang, Xiao-Hua; Wang, Yun-Peng; Li, Ji-Ping; Li, Yong-Jie

2017-06-01

Postural instability and gait disorder (PIGD) in Parkinson disease (PD) has been a great challenge in clinical practice because PIGD is closely linked to major morbidity and mortality in PD. Pedunculopontine nucleus (PPN) has been considered as a potential promising target for deep brain stimulation (DBS) in the treatment of PIGD. A meta-analysis of individual patient data was performed to assess the effects of PPN DBS on PIGD in patients with PD and explore the factors predicting good outcome. According to the study strategy, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, and other sources. After searching the literature, 2 investigators independently screened the literature, assessed the quality of the included trials, and extracted the data. The outcome measures included PIGD, freezing of gait, and falling in PD. Then, individual patient data were incorporated into SPSS software for statistical analyses across series. Six studies reporting individual patient data were included for final analysis. PPN DBS significantly improved PIGD as well as freezing of gait and falling after PD, which was depending on the duration of follow-up and types of outcome measures. In addition, patient age, disease duration, levodopa-equivalent dosage, and the choice of unilateral or bilateral stimulation were similar in groups of patients with PD with or without improvement in PIGD after PPN DBS. Our study provides evidence that PPN DBS may improve PIGD, which should be interpreted with caution and needs further verification before making generalization of our results. Copyright © 2017 Elsevier Inc. All rights reserved.

Separating the effect of reward from corrective feedback during learning in patients with Parkinson's disease.

PubMed

Freedberg, Michael; Schacherer, Jonathan; Chen, Kuan-Hua; Uc, Ergun Y; Narayanan, Nandakumar S; Hazeltine, Eliot

2017-06-01

Parkinson's disease (PD) is associated with procedural learning deficits. Nonetheless, studies have demonstrated that reward-related learning is comparable between patients with PD and controls (Bódi et al., Brain, 132(9), 2385-2395, 2009; Frank, Seeberger, & O'Reilly, Science, 306(5703), 1940-1943, 2004; Palminteri et al., Proceedings of the National Academy of Sciences of the United States of America, 106(45), 19179-19184, 2009). However, because these studies do not separate the effect of reward from the effect of practice, it is difficult to determine whether the effect of reward on learning is distinct from the effect of corrective feedback on learning. Thus, it is unknown whether these group differences in learning are due to reward processing or learning in general. Here, we compared the performance of medicated PD patients to demographically matched healthy controls (HCs) on a task where the effect of reward can be examined separately from the effect of practice. We found that patients with PD showed significantly less reward-related learning improvements compared to HCs. In addition, stronger learning of rewarded associations over unrewarded associations was significantly correlated with smaller skin-conductance responses for HCs but not PD patients. These results demonstrate that when separating the effect of reward from the effect of corrective feedback, PD patients do not benefit from reward.

Sensitivity to reward and punishment in Parkinson's disease: an analysis of behavioral patterns using a modified version of the Iowa gambling task.

PubMed

Kobayakawa, Mutsutaka; Tsuruya, Natsuko; Kawamura, Mitsuru

2010-08-01

Studies using the Iowa gambling task (IGT) have shown that patients with Parkinson's disease (PD) make disadvantageous choices characterized by immediate large rewards and delayed larger punishments. These results can be interpreted in two ways: either PD patients are hypersensitive to immediate outcomes and/or insensitive to delayed consequences or PD patients are hypersensitive to rewards and/or insensitive to punishments. In this study, we used a modified IGT in which selection of cards from the disadvantageous decks leads to immediate, small punishments and delayed, smaller rewards and selection of cards from the advantageous decks leads to immediate, large punishments and delayed larger rewards. We then compared the results obtained using this modified IGT with those obtained using the original IGT. If the PD patients were hypersensitive to the immediate outcomes of decisions, they would make disadvantageous choices in both the original and the modified IGTs. Differences between the results of the original and modified tasks would indicate impairments in balancing reward and punishment. In our analysis, PD patients selected advantageous decks and gained as much as normal subjects during the modified IGT, but they selected disadvantageous decks during the original IGT. These results indicate that the decision-making difficulties of PD patients are caused by their inability to balance reward and punishment and their hypersensitivity to reward and/or insensitivity to punishment.

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer.

PubMed

Sheng, Zhixin; Zhu, Xu; Sun, Yanhua; Zhang, Yanxia

2017-08-22

To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects. When compared to docetaxel, anti-PD-1/PD-L1 therapy could significantly improve overall survival (hazard ratio [HR] 0.67, P<0.001) and progression-free survival (HR 0.83, P=0.002) for previously treated patients with advanced NSCLC. Anti-PD-1/PD-L1 therapy produced an overall response rate of 19% in the 2374 evaluable patients. When using docetaxel as the common comparator, indirect comparison of anti-PD-1/PD-L1 therapy versus EGFR-TKIs showed progression-free survival benefit (HR 0.62, P<0.001) and overall survival benefit (HR 0.60, P<0.001) for those patients with EGFR wild-type. Meanwhile, for those EGFR mutant patients, indirect comparison indicated that anti-PD-1/PD-L1 therapy was inferior to EGFR-TKIs therapy in terms of progression-free survival (HR 3.20, P<0.001), but no survival difference (HR 1.30, P=0.18). Anti-PD-1/PD-L1 therapy could produce progression-free survival and overall survival improvement over docetaxel for patients with previously treated NSCLC. For EGFR wild-type patients, anti-PD-1/PD-L1 therapy seemed to prolong progression-free survival and overall survival when compared to EGFR-TKIs. Meanwhile, for these EGFR mutant patients, anti-PD-1/PD-L1 therapy was inferior to EGFR-TKIs therapy in terms of progression-free survival.

Preserved serotonin transporter binding in de novo Parkinson's disease: negative correlation with the dopamine transporter.

PubMed

Strecker, Karl; Wegner, Florian; Hesse, Swen; Becker, Georg-Alexander; Patt, Marianne; Meyer, Philipp M; Lobsien, Donald; Schwarz, Johannes; Sabri, Osama

2011-01-01

Recent imaging and neuropathological studies indicate reduced serotonin transporter (SERT) in advanced Parkinson's disease (PD). However, data on SERT in early PD patients are sparse. Following the hypothesis that the serotonergic system is damaged early in PD, the aim of our study was to investigate SERT availability by means of PET imaging. Since the loss of dopaminergic neurons is the pathologic hallmark of PD and SERT might be associated with psychiatric co-morbidity, we further sought to correlate SERT availability with the availability of dopamine transporter (DAT) and depressive or motor symptoms in early PD. We prospectively recruited nine early PD patients (4 female, 5 male; 42-76 years) and nine age matched healthy volunteers (5 female, 4 male; 42-72 years). Diagnosis of PD was confirmed by the UK brain bank criteria and DAT imaging. SERT availability was measured by means of [11C]DASB PET. For neuropsychiatric assessment done on the day of PET we applied UPDRS parts I, II and III, Beck's Depression Inventory, Hamilton Rating Scale for Depression, Mini-Mental State Examination and Demtect. SERT was not reduced in any of 14 investigated regions of interest in the nine PD patients compared to healthy controls (p>0.13). SERT was negatively associated with DAT in the striatum (r=-0.69; p=0.04) but not within the midbrain. There was no correlation of SERT availability with depressive symptoms. No alteration of SERT binding in our patients suggests that the serotonergic system is remarkably preserved in early PD. Correlation with DAT might point to a compensatory regulation of the serotonergic system in early stages of PD.

Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson's Disease.

PubMed

Rocha, Natalia Pessoa; Assis, Frankcinéia; Scalzo, Paula Luciana; Vieira, Érica Leandro Marciano; Barbosa, Izabela Guimarães; de Souza, Mariana Soares; Christo, Paulo Pereira; Reis, Helton José; Teixeira, Antonio Lucio

2018-02-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses. Peripheral blood was drawn on the same day of the clinical assessment and submitted to plasma separation for enzyme-linked immunosorbent assay or cytometric bead array. Immunophenotyping analyses of the peripheral blood were performed by flow cytometry. We found that patients with PD presented peripheral immune changes evidenced by decreased percentage of T lymphocytes (CD3+ cells), especially activated T lymphocytes (CD4+CD25+ cells), when compared with controls. In line with these results, we also found decreased plasma levels of the cytokines IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A in the PD group. In vitro experiments demonstrated that the production of cytokines by peripheral blood mononuclear cells harvested from healthy young donors was reduced after exposure to the anti-parkinsonian drugs levodopa and pramipexole. Our data corroborate the hypothesis that immunological mechanisms are involved in PD. It is not clear whether the differences that we have found are due to adaptive mechanisms or to changes associated with PD, including pharmacological treatment, or even directly related to the disease pathophysiology. Future studies are needed in this regard.

Mobile phone applications in Parkinson's disease: A systematic review.

PubMed

Linares-Del Rey, M; Vela-Desojo, L; Cano-de la Cuerda, R

2017-05-23

Parkinson's disease (PD) is the second most common neurodegenerative disease. However, diagnosing, assessing, and treating these patients is a complex process requiring continuous monitoring. In this context, smartphones may be useful in the management of patients with PD. The purpose of this study is to perform a systematic review of the literature addressing the use of mobile phone applications (apps) in PD. We conducted a literature search of articles published in English or Spanish between 2011 and 2016 analysing or validating apps specifically designed for or useful in PD. In addition, we searched for apps potentially useful for PD patients in the leading app stores. The literature and app searches yielded a total of 125 apps, 56 of which were classified as potentially useful in PD and 69 as specifically designed for PD (23 information apps, 29 assessment apps, 13 treatment apps, and 4 assessment and treatment apps). Numerous mobile apps are potentially useful in or specifically designed for PD management. However, scientific evidence of their usefulness is scarce and of poor quality. Further studies are needed to validate these tools and regulate their use. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

PD-1+ CD8+ T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients

PubMed Central

Wu, X; Zhang, H; Xing, Q; Cui, J; Li, J; Li, Y; Tan, Y; Wang, S

2014-01-01

Background: The blockade of PD-1–PD-L1 pathway is emerging as an effective therapeutic strategy for several advanced cancers. But the immune regulatory role of PD-1–PD-L1 pathway is not clear in colorectal cancer (CRC) patients. This study aims to evaluate the role of PD-1–PD-L1 pathway in CD8+ T-cell functions in tumour-draining lymph nodes (TDLNs) and tumours of CRC patients. Methods: PD-1 expression on CD8+ T cells was examined by flow cytometry, and PD-L1 expression in TDLNs and tumour tissues were examined by immunohistochemistry. Production of IFN-γ, IL-2 and expression of granzyme B, perforin in CD8+ T cells were detected by intracellular staining. Results: PD-1 expression is markedly upregulated on CD8+ T cells in TDLNs and tumours compared with that in peripheral blood. PD-1-expressing CD8+ T cells are competent for production of cytokine (IL-2 and IFN-γ) and perforin in the tumour-free lymph nodes (TFLNs), but exhibit exhausted phenotypes in tumours. In addition, PD-L1 is highly expressed in tumours rather than TFLNs, which is closely correlated with the impairment of IFN-γ production of tumour-infiltrating PD-1+ CD8+ T cells. Conclusions: Our findings suggest a suppressive effect of PD-1 on CD8+ T-cell function in tumours, but not in TFLNs. PMID:25093496

New Onset of Diabetes and Pancreatic Exocrine Insufficiency After Pancreaticoduodenectomy for Benign and Malignant Tumors: A Systematic Review and Meta-analysis of Long-term Results.

PubMed

Beger, Hans G; Poch, Bertram; Mayer, Benjamin; Siech, Marco

2018-02-01

The aim of this study was to assess the frequency and severity of new onset of diabetes mellitus (NODM) and pancreatic exocrine insufficiency (PEI) after pancreaticoduodenectomy (PD) for benign and malignant tumors. When PD is performed on patients for benign tumors, the question of long-term metabolic dysfunctions becomes of importance. Medline/PubMed, Embase, and Cochrane Library were searched for articles reporting results of measuring endocrine and exocrine pancreatic functions after PD. The methodological quality of 19 studies was assessed by means of the Newcastle-Ottawa scale and Moga-Score. The mean weighted overall percentages of NODM and PEI after PD were calculated with a 95% confidence interval (CI). Of 1295 patients, data valid-for-efficacy-analysis are based on 845 patients measuring pancreatic endocrine and on 964 patients determining exocrine functions after PD. The cumulative incidence of NODM was 40 of 275 patients (14.5%; 95% CI: 10.3-18.7) in the benign tumor group, 25 of 161 (15.5%; 95% CI: 9.9-21.2) in the malignant tumor group, and 91 of 409 patients (22.2%; 95% CI: 18.2-26.3) in the benign and malignant tumor group. Comparing the frequency of NODM after PD revealed significant differences between the groups (benign vs benign and malignant P < 0.0121; malignant vs benign and malignant P < 0.0017). Exocrine pancreatic insufficiency was found in the benign tumor group in 76 of 301 patients (25.2%; 95% CI: 20.3-30.7) and in the malignant tumor group in 80 of 163 patients (49.1%, 95% CI: 41.4-56.8) (P < 0.0001). The results of a significant increase of NODM after PD for benign and malignant tumors and a significant decrease of exocrine functions contribute to a rational weighting of metabolic long-term risks following PD.

Serum uric acid levels in patients with Parkinson's disease: A meta-analysis.

PubMed

Wen, Min; Zhou, Bo; Chen, Yun-Hua; Ma, Zhao-Lei; Gou, Yun; Zhang, Chun-Lin; Yu, Wen-Feng; Jiao, Ling

2017-01-01

Lower serum uric acid (UA) levels have been reported as a risk factor in Parkinson's disease (PD). However, the results have been inconsistent so far. The aim of the present study was to clarify the potential relationship of uric acid with PD. Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger's regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0. Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = -0.65, 95% CI [-0.84, -0.46], Z = 6.75, p <0.001; Non-Asia: SMD = -0.25, 95% CI [-0.43, -0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = -0.53, 95% CI [-0.70, -0.35], z = 5.98, p <0.001; men: SMD = -0.66, 95% CI [-0.87, -0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001). Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the disease progresses. Thus it might be a potential biomarker to indicate the risk and progression of PD.

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali.

PubMed

Kone, Abdoulaye K; Sagara, Issaka; Thera, Mahamadou A; Dicko, Alassane; Guindo, Aldiouma; Diakite, Seidina; Kurantsin-Mills, Joseph; Djimde, Abdoulaye; Walcourt, Asikiya; Doumbo, Ogabara

2010-11-21

Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT.

APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression.

PubMed

Paul, Kimberly C; Rausch, Rebecca; Creek, Michelle M; Sinsheimer, Janet S; Bronstein, Jeff M; Bordelon, Yvette; Ritz, Beate

2016-04-02

Cognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD. Here, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients. We relied on 634 PD patients and 879 controls to examine gene-PD susceptibility associations, and nested longitudinal cohort of 246 patients from the case-control study, which followed patients on average 5 years and 7.5 years into disease. We repeatedly assessed cognitive symptom progression with the MMSE and conducted a full neuropsychological battery on a subset of 183 cognitively normal patients. We used repeated-measures regression analyses to assess longitudinal associations between genotypes and cognitive progression scores. The MAPT H1 haplotype was associated with PD susceptibility. APOE 4 carriers (ɛ4+) (p = 0.03) and possibly COMT Met/Met (p = 0.06) carriers exhibited faster annual decline on the MMSE. Additionally, APOEɛ4+ carriers showed faster decline in many of the neuropsychological test scores. No such differences in neuropsychological outcomes were seen for the COMT genotypes. This work supports a growing set of research identifying overlapping etiology and pathology between synucleinopathies, such as PD, Alzheimer's disease, and tauopathies, especially in the context of cognitive dysfunction in PD. We provide support for the argument that APOE ɛ4+ and COMT Met/Met genotypes can be used as predictors of faster cognitive decline in PD.

[Analysis of psychological factors influencing peritoneal dialysis selection].

PubMed

Ponz Clemente, E; Martínez Ocaña, J C; Marquina Parra, D; Blasco Cabañas, C; Grau Pueyo, G; Mañé Buixó, N; García García, M

2010-01-01

Peritoneal dialysis (PD) is not frequently used in our setting. To analyze the psychological factors involved in the choice of renal replacement therapy (RRT). A prospective observational study of stable patients without cognitive or sensory deficits who were informed about RRT from January 2004 to July 2006 and agreed to participate. The patients were given and completed the Beck Depression Inventory and the Eysenck personality questionnaire. Clinical and sociodemographic data and RRT choice were recorded. End of follow-up: 2007/10/31. 44 patients were studied: age, 65.4 +/- 13.1 years, 48% male, 34% diabetic. When choosing RRT, 36% of patients had symptoms of depression. Neither depression symptoms nor personality traits were related to the choice of dialysis type. The youngest patients chose PD (41%). After a mean followup of 8 +/- 8 months, 70% of patients started RRT (68% haemodialysis [HD], 32% PD). None of the patients who chose HD changed their mind, but 3 of the 13 patients (23%) who chose PD finally commenced HD, usually in the context of a worsening of the disease. Half of the patients with depression symptoms when choosing PD and a third of the patients with higher levels of neuroticism changed their decision and finally opted for HD. When choosing RRT, the prevalence of depression symptoms is high. Neither depression nor personality traits influenced the initial choice of RRT, although these factors may be involved in subsequent changes to the decision.

Refractive index and its impact on pseudophakic dysphotopsia.

PubMed

Radmall, Bryce R; Floyd, Anne; Oakey, Zack; Olson, Randall J

2015-01-01

It has been shown that the biggest dissatisfier for uncomplicated cataract surgery patients is pseudophakic dysphotopsia (PD). While edge design of an intraocular lens (IOL) impacts this problem, refractive index is still controversial as to its impact. This retrospective cohort study was designed to determine the role of increasing refractive index in PD. This study was conducted at the John A. Moran Eye Center, University of Utah, USA. A retrospective chart review identified patients who received one of two hydrophobic acrylic single piece IOLs (AcrySof WF SP [SN60WF] or Tecnis SP [ZCB00]), which differed mainly by refractive index (1.55 versus 1.47). Eighty-seven patients who had received implantation of a one-piece hydrophobic acrylic IOL were enrolled. Patients were included if the surgery had been uncomplicated and took place at least a year before study participation. All eligible patients had 20/20 best corrected vision, without any disease known to impact visual quality. In addition to conducting a record review, the enrolled patients were surveyed for PD, using a modified National Eye Institute Visual Function questionnaire, as well as for overall satisfaction with visual quality. Statistical analysis demonstrated no difference between the two cohorts regarding PD, general visual function, and overall visual satisfaction. The study suggests that with the two IOLs assessed, increasing the refractive index does not increase incidence of PD or decrease overall visual satisfaction.

Treatment of complicated parapneumonic pleural effusion and pleural parapneumonic empyema.

PubMed

Rodríguez Suárez, Pedro; Freixinet Gilart, Jorge; Hernández Pérez, José María; Hussein Serhal, Mohamed; López Artalejo, Antonio

2012-07-01

We performed this observational prospective study to evaluate the results of the application of a diagnostic and therapeutic algorithm for complicated parapneumonic pleural effusion (CPPE) and pleural parapneumonic empyema (PPE). From 2001 to 2007, 210 patients with CPPE and PPE were confirmed through thoracocentesis and treated with pleural drainage tubes (PD), fibrinolytic treatment or surgical intervention (videothoracoscopy and posterolateral thoracotomy). Patients were divided into 3 groups: I (PD); II (PD and fibrinolytic treatment); IIIa (surgery after PD and fibrinolysis), and IIIb (direct surgery). The statistical study was done by variance analysis (ANOVA), χ2 and Fisher exact test. The presence of alcohol or drug consumption, smoking and chronic obstructive pulmonary disease (COPD) were strongly associated with a great necessity for surgical treatment. The IIIa group was associated with increased drainage time, length of stay and complications. No mortality was observed. The selective use of PD and intrapleural fibrinolysis makes surgery unnecessary in more than 75% of cases. The selective use of PD and fibrinolysis avoids surgery in more than 75% of cases. However, patients who require surgery have more complications, longer hospital stay, and more days on PD and they are more likely to require admittance to the Intensive Care Unit.

Genetic susceptibility and periodontal disease: a retrospective study on a large italian sample.

PubMed

Tettamanti, L; Gaudio, R M; Iapichino, A; Mucchi, D; Tagliabue, A

2017-01-01

Periodontal disease (PD) is a multifactorial illness in which environment and host interact. The genetic component plays a key role in the onset of PD. In fact the genetic compound can modulate the inflammation of the mucous membranes and the loss of alveolar bone. The genetics of PD is not well understood. Previous studies suggest a strong association between PD occurrence and individual genetic profile. The role of genetic susceptibility could impact on the clinical manifestations of PD, and consequently on prevention and therapy. Genetic polymorphisms of VRD, IL6 and IL10 were investigated in Italian adults affected by PD. 571 cases classified according the criteria of the American Academy of Periodontology were included. All patients were Italian coming from three areas according to italian institute of statistics (ISTAT) (www.istat.it/it/archivio/regioni). The sample comprised 379 patients from North (66%), 152 from Central (26%) and 40 of South (8%). No significant differences were found among allele distribution. Chronic PD is a complex disease caused by a combination of genetic susceptibility, patients habits (oral hygiene, smoking, alcohol consumption) and oral pathogens. In our report no differences were detected among three Italian regions in allele distribution.

Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations.

PubMed

Bertrand, Josie-Anne; Bedetti, Christophe; Postuma, Ronald B; Monchi, Oury; Génier Marchand, Daphné; Jubault, Thomas; Gagnon, Jean-François

2012-12-01

Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions. Copyright © 2012 Movement Disorder Society.

FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients with Non-Small-Cell Lung Cancer.

PubMed

Spigel, David R; Chaft, Jamie E; Gettinger, Scott; Chao, Bo H; Dirix, Luc; Schmid, Peter; Chow, Laura Q M; Hicks, Rodney J; Leon, Larry; Fredrickson, Jill; Kowanetz, Marcin; Sandler, Alan; Funke, Roel; Rizvi, Naiyer A

2018-05-15

The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab, Day 1 (21-day cycles). Primary endpoint: investigator-assessed modified Response Evaluation Criteria in Solid Tumors (mRECIST), objective response rate (ORR; RECIST v1.1). Secondary endpoints: overall survival, progression-free survival, duration of response, safety. Patients (n=138) were enrolled (137 evaluable for response: Cohort 1, n=31; Cohort 2, n=93; Cohort 3, n=13). Investigator-assessed ORR was 32%, 21%, and 23% for Cohorts 1, 2, and 3, respectively. Treatment-related adverse events (TRAEs) were reported in 81%, 67%, and 69% of patients, respectively, including grade 3-4 TRAEs in 16%, 19%, and 15%. Moreover, 88.6% (n=86/97) paired baseline tumor samples had <5% change in TC/IC PD-L1 expression over time. Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line; front-line trials are ongoing, confirming these favorable results. Copyright © 2018. Published by Elsevier Inc.

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

PubMed

Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer.

PubMed

Song, Minmin; Chen, Defeng; Lu, Biyan; Wang, Chenliang; Zhang, Junxiao; Huang, Lanlan; Wang, Xiaoyan; Timmons, Christine L; Hu, Jun; Liu, Bindong; Wu, Xiaojian; Wang, Lei; Wang, Jianping; Liu, Huanliang

2013-01-01

Programmed death ligand-1 (PD-L1) has been identified as a factor associated with poor prognosis in a range of cancers, and was reported to be mainly induced by PTEN loss in gliomas. However, the clinical effect of PD-L1 and its regulation by PTEN has not yet been determined in colorectal cancer (CRC). In the present study, we verified the regulation of PTEN on PD-L1 and further determined the effect of PTEN on the correlation between PD-L1 expression and clinical parameters in CRC. RNA interference approach was used to down-regulate PTEN expression in SW480, SW620 and HCT116 cells. It was showed that PD-L1 protein, but not mRNA, was significantly increased in cells transfected with siRNA PTEN compared with the negative control. Moreover, the capacity of PTEN to regulate PD-L1 expression was not obviously affected by IFN-γ, the main inducer of PD-L1. Tissue microarray immunohistochemistry was used to detect PD-L1 and PTEN in 404 CRC patient samples. Overexpression of PD-L1 was significantly correlated with distant metastasis (P<0.001), TNM stage (P<0.01), metastatic progression (P<0.01) and PTEN expression (P<0.001). Univariate analysis revealed that patients with high PD-L1 expression had a poor overall survival (P<0.001). However, multivariate analysis did not support PD-L1 as an independent prognostic factor (P = 0.548). Univariate (P<0.001) and multivariate survival (P<0.001) analysis of 310 located CRC patients revealed that high level of PD-L1 expression was associated with increased risks of metastatic progression. Furthermore, the clinical effect of PD-L1 on CRC was not statistically significant in a subset of 39 patients with no PTEN expression (distant metastasis: P = 0.102; TNM stage: P = 0.634, overall survival: P = 0.482). PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis. This clinical manifestation may be partly associated with PTEN expression.

Future of anti-PD-1/PD-L1 applications: Combinations with other therapeutic regimens.

PubMed

Song, Mengjia; Chen, Xinfeng; Wang, Liping; Zhang, Yi

2018-04-01

Programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) blockade has shown promising effects in cancer immunotherapy. Removing the so-called " brakes" on T cell immune responses by blocking the PD-1/PD-L1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients. However, 30%-60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site, immunosuppressive factors in the tumor microenvironment (TME), and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.

Peritoneal Dialysis-Related Peritonitis: Atypical and Resistant Organisms.

PubMed

Cho, Yeoungjee; Struijk, Dirk Gijsbert

2017-01-01

Peritoneal dialysis (PD)-related peritonitis remains to be one of the most frequent and serious complications of PD. In this study, existing literature has been reviewed on PD peritonitis caused by atypical organisms and antibiotic resistant organisms and their impact on patient outcomes. Although uncommon, delay in recognition of PD peritonitis caused by atypical organisms can lead to poor patient outcomes if there is a delay in diagnosis and implementation of appropriate treatment. There is also a large difference in prevalence of antibiotic-resistant infections across the world with variable impact on reported patient-level outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Epidemiology and outcome of acute pancreatitis in end-stage renal disease dialysis patients: a 10-year national cohort study.

PubMed

Chen, Hung-Jui; Wang, Jhi-Joung; Tsay, Wen-Ing; Her, Shwu-Huey; Lin, Cheng-Heng; Chien, Chih-Chiang

2017-10-01

The objective of this study is to determine the incidence and severity of acute pancreatitis (AP) in patients with end-stage renal disease (ESRD) on dialysis and whether the dialysis modality [hemodialysis (HD) versus peritoneal dialysis (PD)] confers a higher risk for AP as well as complications or mortality related to AP. We analyzed national health insurance claims data of 67 078 ESRD patients initiating dialysis between 1999 and 2007 in Taiwan. All patients were followed up from the start of their dialysis to first AP diagnosis, death, end of dialysis or 31 December 2008. Cox proportional hazards models were used to identify risk factors. The cumulative incidence rates of AP were 0.6, 1.7, 2.6, 3.4 and 4% at 1, 3, 5, 7 and 9 years, respectively. ESRD patients on HD and PD had an AP incidence of 5.11 and 5.86 per 1000 person-years, respectively. Independent risk factors for AP in this population were being elderly, being female, having biliary stones or liver disease, and being on PD. Severe AP occurred in 44.9% of the HD patients and in 36% of the PD patients. Patients with AP on HD had a higher incidence of upper gastrointestinal (UGI) bleeding than those on PD (P = 0.002). In contrast, those with AP on PD had a higher incidence of need for total parenteral nutrition (TPN) support than those on HD (P = 0.072). Overall in-hospital mortality was 8.1%. The risk factors for mortality after an AP attack were male gender, increased age, AP severity, and the presence of diabetes mellitus or liver disease. ESRD patients on PD were at higher risk for AP than those on HD. HD patients with AP attacks had a greater incidence of UGI bleeding and PD patients with AP attacks a more frequent need for TPN support. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The Role of the Frontal Lobe in Complex Walking Among Patients With Parkinson's Disease and Healthy Older Adults: An fNIRS Study.

PubMed

Maidan, Inbal; Nieuwhof, Freek; Bernad-Elazari, Hagar; Reelick, Miriam F; Bloem, Bas R; Giladi, Nir; Deutsch, Judith E; Hausdorff, Jeffery M; Claassen, Jurgen A H; Mirelman, Anat

2016-11-01

Gait is influenced by higher order cognitive and cortical control mechanisms. Functional near infrared spectroscopy (fNIRS) has been used to examine frontal activation during walking in healthy older adults, reporting increased oxygenated hemoglobin (HbO2) levels during dual task walking (DT), compared with usual walking. To investigate the role of the frontal lobe during DT and obstacle negotiation, in healthy older adults and patients with Parkinson's disease (PD). Thirty-eight healthy older adults (mean age 70.4 ± 0.9 years) and 68 patients with PD (mean age 71.7 ± 1.1 years,) performed 3 walking tasks: (a) usual walking, (b) DT walking, and (c) obstacles negotiation, with fNIRS and accelerometers. Linear-mix models were used to detect changes between groups and within tasks. Patients with PD had higher activation during usual walking (P < .030). During DT, HbO2 increased only in healthy older adults (P < .001). During obstacle negotiation, HbO2 increased in patients with PD (P = .001) and tended to increase in healthy older adults (P = .053). Higher DT and obstacle cost (P < .003) and worse cognitive performance were observed in patients with PD (P = .001). A different pattern of frontal activation during walking was observed between groups. The higher activation during usual walking in patients with PD suggests that the prefrontal cortex plays an important role already during simple walking. However, higher activation relative to baseline during obstacle negotiation and not during DT in the patients with PD demonstrates that prefrontal activation depends on the nature of the task. These findings may have important implications for rehabilitation of gait in patients with PD. © The Author(s) 2016.

REM Sleep Behavior Disorder and Cognitive Impairment in Parkinson's Disease.

PubMed

Jozwiak, Natalia; Postuma, Ronald B; Montplaisir, Jacques; Latreille, Véronique; Panisset, Michel; Chouinard, Sylvain; Bourgouin, Pierre-Alexandre; Gagnon, Jean-François

2017-08-01

REM sleep behavior disorder (RBD) is a parasomnia affecting 33% to 46% of patients with Parkinson's disease (PD). The existence of a unique and specific impaired cognitive profile in PD patients with RBD is still controversial. We extensively assessed cognitive functions to identify whether RBD is associated with more severe cognitive deficits in nondemented patients with PD. One hundred sixty-two participants, including 53 PD patients with RBD, 40 PD patients without RBD, and 69 healthy subjects, underwent polysomnography, a neurological assessment and an extensive neuropsychological exam to assess attention, executive functions, episodic learning and memory, visuospatial abilities, and language. PD patients with RBD had poorer and clinically impaired performance in several cognitive tests compared to PD patients without RBD and healthy subjects. These two latter groups were similar on all cognitive measures. Mild cognitive impairment (MCI) diagnosis frequency was almost threefold higher in PD patients with RBD compared to PD patients without RBD (66% vs. 23%, p < .001). Moreover, subjective cognitive decline was reported in 89% of PD patients with RBD compared to 58% of PD patients without RBD (p = .024). RBD in PD is associated with a more impaired cognitive profile and higher MCI diagnosis frequency, suggesting more severe and widespread neurodegeneration. This patient subgroup and their caregivers should receive targeted medical attention to better detect and monitor impairment and to enable the development of management interventions for cognitive decline and its consequences. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

[Implications of TCGA Network Data on 2nd Generation Immunotherapy Concepts Based on PD-L1 and PD-1 Target Structures].

PubMed

Peters, I; Tezval, H; Kramer, M W; Wolters, M; Grünwald, V; Kuczyk, M A; Serth, J

2015-11-01

The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein level in an appropriately sized patient population and evaluate the clinical significance. © Georg Thieme Verlag KG Stuttgart · New York.

Imposed Faster and Slower Walking Speeds Influence Gait Stability Differently in Parkinson Fallers.

PubMed

Cole, Michael H; Sweeney, Matthew; Conway, Zachary J; Blackmore, Tim; Silburn, Peter A

2017-04-01

To evaluate the effect of imposed faster and slower walking speeds on postural stability in people with Parkinson disease (PD). Cross-sectional cohort study. General community. Patients with PD (n=84; 51 with a falls history; 33 without) and age-matched controls (n=82) were invited to participate via neurology clinics and preexisting databases. Of those contacted, 99 did not respond (PD=36; controls=63) and 27 were not interested (PD=18; controls=9). After screening, a further 10 patients were excluded; 5 had deep brain stimulation surgery and 5 could not accommodate to the treadmill. The remaining patients (N=30) completed all assessments and were subdivided into PD fallers (n=10), PD nonfallers (n=10), and age-matched controls (n=10) based on falls history. Not applicable. Three-dimensional accelerometers assessed head and trunk accelerations and allowed calculation of harmonic ratios and root mean square (RMS) accelerations to assess segment control and movement amplitude. Symptom severity, balance confidence, and medical history were established before participants walked on a treadmill at 70%, 100%, and 130% of their preferred speed. Head and trunk control was lower for PD fallers than PD nonfallers and older adults. Significant interactions indicated head and trunk control increased with speed for PD nonfallers and older adults, but did not improve at faster speeds for PD fallers. Vertical head and trunk accelerations increased with walking speed for PD nonfallers and older adults, while the PD fallers demonstrated greater anteroposterior RMS accelerations compared with both other groups. The results suggest that improved gait dynamics do not necessarily represent improved walking stability, and this must be respected when rehabilitating gait in patients with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Subjective and psychological well-being in Parkinson's Disease: A systematic review.

PubMed

Vescovelli, F; Sarti, D; Ruini, C

2018-04-25

The aim of this review is to summarize studies investigating subjective and psychological well-being in patients with Parkinson's disease (PD). A systematic and integrative review according to PRISMA criteria was performed with a literature search from inception up to September 2017 in multidisciplinary databases (PubMED, Scopus, Web of Knowledge) by combining together key words related to PD and well-being. Studies were included if: their full-text was available; they involved PD patients; focused on the selected positive dimensions; written in English. Case studies, conference proceedings, abstract, dissertations, book chapters, validation studies and reviews were excluded. Data extracted from the studies included sample characteristics, the positive dimension investigated, type of measure, study aims, design and results. One reviewer extracted details and commented results with other reviewers. The studies' quality was assessed following Kmet, Lee, and Cook. Out of 1425 studies extracted, 12 studies (9 quantitative, 2 qualitative, 1 mixed methods) involving 2204 patients with PD were included. Most of the studies had a cross-sectional design and/or evaluated the effect of physical rehabilitation on well-being. Articles documented that the illness could impair well-being for its progressive impact on patients' motor autonomy. Preserving motor and musculoskeletal functioning facilitate patients' experience of well-being, social contribution and the maintenance of their job. Research on positive resources in PD is still scarce compared to other chronic illnesses. The few available investigations suggest the need of preserving motor abilities by proper rehabilitation programs for maintaining and/or promoting patients' well-being and life engagement. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Is the Berg Balance Scale an effective tool for the measurement of early postural control impairments in patients with Parkinson's disease? Evidence from Rasch analysis.

PubMed

La Porta, F; Giordano, A; Caselli, S; Foti, C; Franchignoni, F

2015-12-01

It is unclear whether the BBS is an effective tool for the measurement of early postural control impairments in patients with Parkinson's disease (PD). The aim of this paper was to evaluate BBS' content validity, internal construct validity, reliability and targeting in patients with PD within the Rasch analysis framework. Observational, cross-sectional study. Outpatient Rehabilitation Unit. A sample of 285 outpatients with PD. The content validity of the BBS was assessed using standard linking techniques. The BBS was administered by trained physiotherapists. The data collected then underwent Rasch analysis. Content validity analysis showed a lack of items assessing postural responses to tripping and slips and stability during walking. On Rasch analysis, the BBS failed the requirements of monotonicity, local independence, unidimensionality and invariance. After rescoring 7 items, grouping of locally dependent items into testlets, and deletion of the static sitting balance item because mistargeted and underdiscriminating, the Rasch-modified BBS for PD (BBS-PD) showed adequate internal construct validity (χ(2)24=39.693; P=0.023), including absence of differential item functioning (DIF) across gender and age, and was, as a whole, sufficiently precise for individual person measurement (PSI=0.894). However, the scale was not well targeted to the sample in view of the prevalence of higher scores. This study demonstrated the internal construct validity and reliability of the BBS-PD as a measurement tool for patients with PD within the Rasch analysis framework. However, the lack of items critical to the assessment of postural control impairments typical of PD, affected negatively the targeting, so that a significant percentage of patients was located in the higher ability range of the measurement continuum, where precision of measurement is reduced. These findings suggest that the BBS, even if modified, may not be an effective tool for the measurement of early postural control in patients with PD.

Home visit program improves technique survival in peritoneal dialysis.

PubMed

Martino, Francesca; Adıbelli, Z; Mason, G; Nayak, A; Ariyanon, W; Rettore, E; Crepaldi, Carlo; Rodighiero, Mariapia; Ronco, Claudio

2014-01-01

Peritoneal dialysis (PD) is a home therapy, and technique survival is related to the adherence to PD prescription at home. The presence of a home visit program could improve PD outcomes. We evaluated its effects on clinical outcome during 1 year of follow-up. This was a case-control study. The case group included all 96 patients who performed PD in our center on January 1, 2013, and who attended a home visit program; the control group included all 92 patients who performed PD on January 1, 2008. The home visit program consisted of several additional visits to reinforce patients' confidence in PD management in their own environment. Outcomes were defined as technique failure, peritonitis episode, and hospitalization. Clinical and dialysis features were evaluated for each patient. The case group was significantly older (p = 0.048), with a lower grade of autonomy (p = 0.033), but a better hemoglobin level (p = 0.02) than the control group. During the observational period, we had 11 episodes of technique failure. We found a significant reduction in the rate of technique failure in the case group (p = 0.004). Furthermore, survival analysis showed a significant extension of PD treatment in the patients supported by the home visit program (52 vs. 48.8 weeks, p = 0.018). We did not find any difference between the two groups in terms of peritonitis and hospitalization rate; however, trends toward a reduction of Gram-positive peritonitis rates as well as prevalence and duration of hospitalization related to PD problems were identified in the case group. The retrospective nature of the analysis was a limitation of this study. The home visit program improves the survival of PD patients and could reduce the rate of Gram-positive peritonitis and hospitalization. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=365168.

Depression and major depressive disorder in patients with Parkinson's disease.

PubMed

Inoue, Takeshi; Kitagawa, Mayumi; Tanaka, Teruaki; Nakagawa, Shin; Koyama, Tsukasa

2010-01-15

The prevalence of depression in Parkinson's disease (PD) varies greatly. In this study, we investigated major depressive disorder (MDD) and depressive symptoms without MDD in patients with PD. The psychopathological characteristics of depressive symptoms were assessed by a psychiatric interview. A total of 105 Japanese patients with PD without dementia were included. The Japanese version of the Beck Depression Inventory-II (BDI-II) with a cutoff score of 13/14 was used to screen for depression. Using a structured interview, a comprehensive psychiatric evaluation of patients with BDI-II scores >13 (high BDI patients) was completed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR. Forty patients (38%) had a BDI-II >13, but 29 did not show any depressed mood. Five cases met the criteria for MDD (three current, two past) and one patient was diagnosed with minor depressive disorder. A slight depressed mood that was associated with worrying about PD was seen in 6 of 34 patients without any depressive disorder and fluctuated with aggravation of PD symptoms in two of these patients. For the diagnosis of MDD, the number of positive items from the DSM-IV-TR definition of MDD is most important and useful for differentiating MDD and non-MDD. The low-prevalence rate of MDD in our patient population suggests that PD may be a psychological stressor for MDD, but does not necessarily induce MDD.

Impact of a Health Management Program on Healthcare Outcomes among Patients on Augmentation Therapy for Alpha 1-Antitrypsin Deficiency: An Insurance Claims Analysis.

PubMed

Campos, Michael A; Runken, Michael C; Davis, Angela M; Johnson, Michael P; Stone, Glenda A; Buikema, Ami R

2018-04-01

Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder which reduces serum alpha 1-antitrypsin (AAT or alpha1-proteinase inhibitor, A1PI) and increases the risk of chronic obstructive pulmonary disease (COPD). Management strategies include intravenous A1PI augmentation, and, in some cases, a health management program (Prolastin Direct ® ; PD). This study compared clinical and economic outcomes between patients with and without PD program participation. This retrospective study included commercial and Medicare Advantage health insurance plan members with ≥ 1 claim with diagnosis codes for COPD and ≥ 1 medical or pharmacy claim including A1PI (on index date). Outcomes were compared between patients receiving only Prolastin ® or Prolastin ® -C (PD cohort) and patients who received a different brand without PD (Comparator cohort). Demographic and clinical characteristics were captured during 6 months pre-index. Post-index exacerbation episodes and healthcare utilization and costs were compared between cohorts. The study sample comprised 445 patients (n = 213 in PD cohort; n = 232 in Comparator cohort), with a mean age 55.5 years, 50.8% male, and 78.9% commercially insured. The average follow-up was 822 days (2.25 years), and the average time on A1PI was 747 days (2.04 years). Few differences were observed in demographic or clinical characteristics. Adjusting for differences in patient characteristics, the rate of severe exacerbation episodes was reduced by 36.1% in the PD cohort. Adjusted total annual all-cause costs were 11.4% lower, and adjusted mean respiratory-related costs were 10.6% lower in the PD cohort than the Comparator cohort. Annual savings in all-cause total costs in the PD cohort relative to the Comparator cohort was US$25,529 per patient, largely due to significantly fewer and shorter hospitalizations. These results suggest that comprehensive health management services may improve both clinical and economic outcomes among patients with COPD and AATD who receive augmentation therapy. Grifols Shared Services of North America, Inc.

Motor, psychiatric and fatigue features associated with nutritional status and its effects on quality of life in Parkinson's disease patients.

PubMed

Fereshtehnejad, Seyed-Mohammad; Ghazi, Ladan; Shafieesabet, Mahdiyeh; Shahidi, Gholam Ali; Delbari, Ahmad; Lökk, Johan

2014-01-01

Parkinson's disease (PD) patients are more likely to develop impaired nutritional status because of the symptoms, medications and complications of the disease. However, little is known about the determinants and consequences of malnutrition in PD. This study aimed to investigate the association of motor, psychiatric and fatigue features with nutritional status as well as the effects of malnutrition on different aspects of quality of life (QoL) in PD patients. One hundred and fifty patients with idiopathic PD (IPD) were recruited in this study. A demographic checklist, the Unified Parkinson's Disease Rating Scale (UPDRS), the Hospital Anxiety and Depression Scale (HADS) and the Fatigue Severity Scale (FSS) were completed through face-to-face interviews and clinical examinations. The health-related QoL (HRQoL) was also evaluated by means of the Parkinson's Disease Questionnaire (PDQ-39). For evaluation of nutritional status, the Mini Nutritional Assessment (MNA) questionnaire was applied together with anthropometric measurements. Thirty seven (25.3%) patients were at risk of malnutrition and another 3 (2.1%) were malnourished. The total score of the UPDRS scale (r =  -0.613, P<0.001) and PD duration (r =  -0.284, P = 0.002) had a significant inverse correlation with the total MNA score. The median score of the Hoehn and Yahr stage was significantly higher in PD patients with abnormal nutritional status [2.5 vs. 2.0; P<0.001]. More severe anxiety [8.8 vs. 5.9; P = 0.002], depression [9.0 vs. 3.6; P<0.001] and fatigue [5.4 vs. 4.2; P<0.001] were observed in PD patients with abnormal nutritional status. Except for stigma, all other domains of the PDQ-39 were significantly correlated with the total score of the MNA. Our study demonstrates that disease duration, severity of motor and psychiatric symptoms (depression, anxiety) and fatigue are associated with nutritional status in PD. Different aspects of the HRQoL were affected by patients' nutritional status especially the emotional well-being and mobility domains.

Predictive factors for a one-year improvement in nontuberculous mycobacterial pulmonary disease: An 11-year retrospective and multicenter study.

PubMed

Cadelis, Gilbert; Ducrot, Rodolphe; Bourdin, Arnaud; Rastogi, Nalin

2017-08-01

Nontuberculous mycobacterial pulmonary disease (NTM-PD) has become an emerging infectious disease and is responsible for more deaths than tuberculosis in industrialized countries. NTM-PD mortality remains high in some series reportedly ranging from 25% to 40% at five years and often due to unfavorable evolution of NTM-PD despite established treatment. The purpose of our study was to search for early factors that could predict the favorable or unfavorable evolution of NTM-PD at the first year of treatment. In this retrospective and multicenter study, we selected 119 patients based on clinical, radiological and microbiological data from 2002 to 2012 from three French university hospitals (Guadeloupe, Martinique, Montpellier) with definite (meeting the criteria of the American Thoracic Society and the Infectious Disease Society of America in 2007; ATS/IDSA) or probable (one positive sputum culture) NTM-PD. We compared two patient groups: those who improved at one year (clinical symptoms, radiological lesions and microbiology data) and those who did not improve at one year. The data were analyzed for all patients as well as for subgroups by gender, HIV-positive patients, and Mycobacterium avium complex (MAC) infection. The average patient age was 50 years ± 19.4; 58% had respiratory comorbidities, 24% were HIV positive and 19% had cystic fibrosis. Coughing concerned 66% of patients and bronchiectasis concerned 45%. The most frequently isolated NTM were MAC (46%). 57% (n = 68) of patients met the ATS criteria and improved status concerned 38.6% (n = 46). The improvement factors at one year of NTM-PD were associated with the duration of ethambutol treatment: (Odds ratio adjusted [ORa]: 2.24, 95% Confidence interval [CI]; 2.11-3.41), HIV-positive status: (ORa: 3.23, 95% CI; 1.27-8.45), and male gender: (ORa: 2.34, 95% CI; 1.26-8.16). For the group with NTM-PD due to MAC, improvement was associated with the duration of macrolide treatment (ORa: 3.27, 95% CI; 1.88-7.30) and an age <50 years (ORa: 1.88, 95% CI; 1.55-8.50). In this retrospective multicenter study, improvement at one year in patients with definite or probable NTM-PD was associated with the duration of ethambutol treatment, HIV-positive status and male gender. For the group of patients infected with MAC, improvement was associated with the duration of macrolide treatment and an age <50 years. Identifying predictors of improvement at one year of NTM-PD is expected to optimize the management of the disease in its early stages.

Effects of various factors on sleep disorders and quality of life in Parkinson's disease.

PubMed

Telarovic, Srdjana; Mijatovic, Dragana; Telarovic, Irma

2015-12-01

In Parkinson's disease (PD), sleep disorders (SD) occur as a result of the neurochemical changes in sleep centres, neurodegenerative changes in dopaminergic neurons, and other factors. The most common SD include excessive daytime sleepiness, insomnia, restless legs syndrome and nocturia. The aim of the study was to compare quality of sleep, as a factor that greatly impacts quality of life (QoL), between PD patients and a control group and to further examine SD in the PD group with focus on incidence and SD types as well as on effects various factors (age, sex, PD characteristics, medication usage) have on these disorders. The study included 110 patients who met the criteria for the diagnosis of PD and 110 age-matched healthy controls. We used the Pittsburgh Sleep Quality Index, PD Sleep Scale, Epworth Sleepiness Scale, PD QoL Questionnaire-8 and PD Questionnaire-39 (items 30 and 33). In the group with PD, we considered the duration of the disease, the stage of disease according to the Hoehn and Yahr scale, medications and their impact on the SD. The average duration of the disease was 6 years and the mean stage was 2.44. The result showed significant differences in the sleep quality between groups. In the PD group, SD differences were also found according to gender, duration of the disease and medication usage. The most common SD were fragmented sleep, insomnia and nocturia. To improve the QoL of PD patients, it is necessary to pay more attention to detecting and solving SD.

Effects of dopaminergic replacement therapy on motor speech disorders in Parkinson's disease: longitudinal follow-up study on previously untreated patients.

PubMed

Rusz, Jan; Tykalová, Tereza; Klempíř, Jiří; Čmejla, Roman; Růžička, Evžen

2016-04-01

Although speech disorders represent an early and common manifestation of Parkinson's disease (PD), little is known about their progression and relationship to dopaminergic replacement therapy. The aim of the current study was to examine longitudinal motor speech changes after the initiation of pharmacotherapy in PD. Fifteen newly-diagnosed, untreated PD patients and ten healthy controls of comparable age were investigated. PD patients were tested before the introduction of antiparkinsonian therapy and then twice within the following 6 years. Quantitative acoustic analyses of seven key speech dimensions of hypokinetic dysarthria were performed. At baseline, PD patients showed significantly altered speech including imprecise consonants, monopitch, inappropriate silences, decreased quality of voice, slow alternating motion rates, imprecise vowels and monoloudness. At follow-up assessment, preservation or slight improvement of speech performance was objectively observed in two-thirds of PD patients within the first 3-6 years of dopaminergic treatment, primarily associated with the improvement of stop consonant articulation. The extent of speech improvement correlated with L-dopa equivalent dose (r = 0.66, p = 0.008) as well as with reduction in principal motor manifestations based on the Unified Parkinson's Disease Rating Scale (r = -0.61, p = 0.02), particularly reflecting treatment-related changes in bradykinesia but not in rigidity, tremor, or axial motor manifestations. While speech disorders are frequently present in drug-naive PD patients, they tend to improve or remain relatively stable after the initiation of dopaminergic treatment and appear to be related to the dopaminergic responsiveness of bradykinesia.

Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with gastric cancer.

PubMed

Savabkar, Sanaz; Azimzadeh, Pedram; Chaleshi, Vahid; Nazemalhosseini Mojarad, Ehsan; Aghdaei, Hamid Asadzadeh

2013-01-01

This study aimed to determine the association between PD-1.5C/T (rs2227981, +7785) and the risk of gastric cancer (GC) in an Iranian population. Gastric cancer is the fourth most common cancer in the world. The programmed death 1 (PD-1) is a member of the CD28 super family. PD-1 is a negative regulator of T-cell effector mechanisms which decrease immune responses against cancer. we conducted case- control study to investigate the association of PD-1.5 C/T polymorphism in 122 GC patients and 166 control individuals. DNA was extracted from blood specimens. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The frequency of CC, CT and TT genotypes was 53.6%, 42.2% and 4.2% in control group and 41%, 54.1% and 4.9% in gastric cancer patients respectively. CC genotype was more frequent in control individuals than in patients but we found no statically significant association. The frequencies of PD-1.5CT genotypes were significantly higher in GC patient compared with control individuals (OR= 1.77, 95% CI= 1.077-2.931; P=0.026). Allele distribution was similar in patients and healthy individuals (p = 0.061).Frequency of C and T alleles was 74.7%, 25.3% in control individuals and 68.03% and 31.97% in gastric cancer patients respectively. These results suggest that PD-1.5 C/T polymorphism may affect the GC risk and prognosis in an Iranian population.

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

PubMed

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

The associations between fatigue, apathy, and depression in Parkinson's disease.

PubMed

Skorvanek, M; Gdovinova, Z; Rosenberger, J; Saeedian, R Ghorbani; Nagyova, I; Groothoff, J W; van Dijk, J P

2015-02-01

Fatigue and apathy are two of the most common and most disabling non-motor symptoms of Parkinson's disease (PD). They have a high coincidence and can often be confused; moreover, their relationship is not fully understood. The aim of our study was to describe the coincidence of apathy with different fatigue domains in the presence/absence of depression and to separately describe the associations of different aspects of primary and secondary fatigue with apathy and other clinical and disease-related factors. A total of 151 non-demented patients with PD were examined using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Starkstein Apathy Scale, Multidimensional Fatigue Inventory (MFI), Beck Depression Inventory-II, and Epworth Sleepiness Scale. The prevalence and severity of fatigue and apathy were significantly higher in depressed PD patients. However, our results show that depression, fatigue, and apathy can be clearly distinguished in PD. Apathy was associated with the MFI's-reduced motivation domain in both depressed and non-depressed patients. However, apathy was associated with mental fatigue aspects only in non-depressed patients, and it was not related to the physical aspects of fatigue in any of the studied groups. Although the pathophysiology of fatigue and apathy in PD is clearly multifactorial, in a proportion of PD patients, these symptoms are associated with depression, dopaminergic depletion in the mesocorticolimbic structures, and disruption of the prefrontal cortex-basal ganglia axis. Therefore, in some PD patients, adequate management of depression and optimal dopaminergic medication may improve both fatigue and apathy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Implementation of enhanced recovery programme after pancreatoduodenectomy: a single-centre UK pilot study.

PubMed

Abu Hilal, Mohammed; Di Fabio, Francesco; Badran, Abdallah; Alsaati, Hani; Clarke, Hannah; Fecher, Imogen; Armstrong, Thomas H; Johnson, Colin D; Pearce, Neil W

2013-01-01

Data on enhanced recovery programmes after pancreatoduodenectomy (ERP-PD) is limited. The aim of this pilot study was to evaluate the feasibility, safety and clinical outcomes of ERP-PD when implemented at a high-volume UK university referral centre. This was an observational single-surgeon case-control study (before-and-after pathway). A total of 20 consecutive patients were prospectively enrolled for the ERP-PD and compared with 24 consecutive patients previously treated during an equal time frame. Patients in the ERP-PD group had a significant shorter time to remove naso-gastric tube (median of 5 vs. 7 days, p = 0.0001), start liquid diet (median of 2 vs. 5 days, p < 0.0001), start solid food (median of 4 vs. 9 days, p < 0.0001), pass stools (median of 6 vs. 7 days, p = 0.002), and had shorter length of stay (median of 8.5 days vs. 13 days, p = 0.015) compared to the pre-pathway group. Postoperative complications were overall less frequent but not significantly different in the ERP-PD group (p = 0.077). No difference in mortality and readmission rates was found. Our findings support the feasibility and safety of ERP-PD. Improved patients' outcomes, significant bed day savings and increase National Health Service productivity are anticipated with implementation of ERP-PD on a larger scale. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Replication and meta-analysis of TMEM132D gene variants in panic disorder

PubMed Central

Erhardt, A; Akula, N; Schumacher, J; Czamara, D; Karbalai, N; Müller-Myhsok, B; Mors, O; Borglum, A; Kristensen, A S; Woldbye, D P D; Koefoed, P; Eriksson, E; Maron, E; Metspalu, A; Nurnberger, J; Philibert, R A; Kennedy, J; Domschke, K; Reif, A; Deckert, J; Otowa, T; Kawamura, Y; Kaiya, H; Okazaki, Y; Tanii, H; Tokunaga, K; Sasaki, T; Ioannidis, J P A; McMahon, F J; Binder, E B

2012-01-01

A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case–control samples (n=1670 cases and n=2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727–rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n=1038 cases and n=2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P=1.4e−8 and P=1.1e−8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations. PMID:22948381

An association of cognitive impairment with diabetes and retinopathy in end stage renal disease patients under peritoneal dialysis.

PubMed

Liao, Jin-Lan; Xiong, Zu-Ying; Yang, Zhi-Kai; Hao, Li; Liu, Gui-Ling; Ren, Ye-Ping; Wang, Qin; Duan, Li-Ping; Zheng, Zhao-Xia; Dong, Jie

2017-01-01

Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD). In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.09[1.11,3.92], 2.89[1.55,5.37], 2.16 [1.15,4.06] and 2.37[1.32,4.22], respectively (all P < 0.05). Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.

Pembrolizumab in the treatment of metastatic non-small cell lung cancer: a review of current evidence

PubMed Central

Rihawi, Karim; Gelsomino, Francesco; Sperandi, Francesca; Melotti, Barbara; Fiorentino, Michelangelo; Casolari, Laura; Ardizzoni, Andrea

2017-01-01

Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors. Pembrolizumab, a highly selective anti-PD-1 humanized monoclonal antibody, was approved by the United States Food and Drug Administration (US FDA) in October 2016 for previously untreated metastatic NSCLC patients whose tumors have high PD-L1 expression, tumor proportion score (TPS) ⩾ 50%, as well as for metastatic NSCLC patients whose tumors express PD-L1 with TPS ⩾ 1% progressing on or after platinum-based chemotherapy. However, many issues remain outstanding, mainly regarding the identification of an optimal biomarker which can help selecting patients more likely to respond to ICPIs. In this review, we discuss the clinical results obtained so far with the anti-PD-1 pembrolizumab in advanced NSCLC, commenting on the role of PD-L1 as a predictive factor and providing an update of the future perspectives. PMID:28818019

Voice characteristics in the progression of Parkinson's disease.

PubMed

Holmes, R J; Oates, J M; Phyland, D J; Hughes, A J

2000-01-01

This study examined the acoustic and perceptual voice characteristics of patients with Parkinson's disease according to disease severity. The perceptual and acoustic voice characteristics of 30 patients with early stage PD and 30 patients with later stage PD were compared with data from 30 normal control subjects. Voice recordings consisted of prolongation of the vowel /a/, scale singing, and a 1-min monologue. In comparison with controls and previously published normative data, both early and later stage PD patients' voices were characterized perceptually by limited pitch and loudness variability, breathiness, harshness and reduced loudness. High modal pitch levels also characterized the voices of males in both early and later stages of PD. Acoustically, the voices of both groups of PD patients demonstrated lower mean intensity levels and reduced maximum phonational frequency ranges in comparison with normative data. Although less clear, the present data also suggested that the PD patients' voices were characterized by excess jitter, a high-speaking fundamental frequency for males and a reduced fundamental frequency variability for females. While several of these voice features did not appear to deteriorate with disease progression (i.e. harshness, high modal pitch and speaking fundamental frequency in males, fundamental frequency variability in females, low intensity and jitter), breathiness, monopitch and monoloudness, low loudness and reduced maximum phonational frequency range were all worse in the later stages of PD. Tremor was the sole voice feature which was associated only with later stage PD.

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

PubMed

Saâda-Bouzid, E; Defaucheux, C; Karabajakian, A; Coloma, V P; Servois, V; Paoletti, X; Even, C; Fayette, J; Guigay, J; Loirat, D; Peyrade, F; Alt, M; Gal, J; Le Tourneau, C

2017-07-01

Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK). We retrospectively compared TGK on immunotherapy and TGK on last treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four French centers. The TGK ratio (TGKR, ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR ≥ 2. From September 2012 to September 2015, 34 patients were identified. Patterns of recurrence included exclusive loco-regional recurrence in 14 patients, exclusive distant metastases in 11 patients, and both in 9 patients. No pseudo-progression was observed. Hyperprogression was observed in 10 patients (29%), including 9 patients with at least a locoregional recurrence, and only 1 patient with exclusively distant metastases. Hyperprogression significantly correlated with a regional recurrence (TGKR ≥ 2: 90% versus TGKR < 2: 37%, P = 0.008), but not with local or distant recurrence. Hyperprogression was associated with a shorter progression-free survival (PFS) according to RECIST (P = 0.003) and irRECIST (P = 0.02), but not with overall survival (P = 0.77). Hyperprogression was observed in 29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated with a shorter PFS. It occurred in 39% of patients with at least a locoregional recurrence and 9% of patients with exclusively distant metastases. No pseudo-progressions were reported. Mechanisms and causality of hyperprogression should further be assessed through prospective controlled studies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-β1, and vascular endothelial growth factor.

PubMed

Abrahams, Alferso C; Habib, Sayed M; Dendooven, Amélie; Riser, Bruce L; van der Veer, Jan Willem; Toorop, Raechel J; Betjes, Michiel G H; Verhaar, Marianne C; Watson, Christopher J E; Nguyen, Tri Q; Boer, Walther H

2014-01-01

Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P < 0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P < 0.001), TGFβ1 (24-fold, P < 0.05), and VEGF (77-fold, P < 0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0 ± 4.5 vs. 0.91 ± 0.92 ng/ml, P < 0.01), while plasma CCN2 levels were not increased. Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study.

Patients with Encapsulating Peritoneal Sclerosis Have Increased Peritoneal Expression of Connective Tissue Growth Factor (CCN2), Transforming Growth Factor-β1, and Vascular Endothelial Growth Factor

PubMed Central

Abrahams, Alferso C.; Habib, Sayed M.; Dendooven, Amélie; Riser, Bruce L.; van der Veer, Jan Willem; Toorop, Raechel J.; Betjes, Michiel G. H.; Verhaar, Marianne C.; Watson, Christopher J. E.; Nguyen, Tri Q.; Boer, Walther H.

2014-01-01

Introduction Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Materials and methods Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Results Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P<0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P<0.001), TGFβ1 (24-fold, P<0.05), and VEGF (77-fold, P<0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0±4.5 vs. 0.91±0.92 ng/ml, P<0.01), while plasma CCN2 levels were not increased. Conclusions Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study. PMID:25384022