Sarcoidosis diagnostic score (SDS): a systematic evaluation to enhance the diagnosis of sarcoidosis.

PubMed

Bickett, Alexandra N; Lower, Elyse E; Baughman, Robert P

2018-05-17

The diagnosis of sarcoidosis is made by the combination of clinical features and biopsy results. The clinical features of sarcoidosis can be quite variable. We developed a Sarcoidosis Diagnostic Score (SDS) to summarize the clinical features of possible sarcoidosis patients. Biopsy confirmed sarcoidosis patients seen during a seven-month time period at the University of Cincinnati Sarcoidosis clinic were prospectively identified. Non-sarcoidosis patients seen at the same clinic were used as controls. Using a modified WASOG organ assessment instrument, we scored all patients for presence of biopsy, one or more highly probable symptom, and one or more at least probable symptom for each area. Two sarcoidosis scores were generated: SDS biopsy (with biopsy) and SDS clinical (without biopsy). The 980 evaluable patients were divided into two cohorts: an initial 600 patients (450 biopsy confirmed sarcoidosis, 150 controls) to establish cut-off values for SDS biopsy and SDS clinical and a validation cohort of 380 patients (103 biopsy confirmed sarcoidosis patients and 277 controls). The best cutoff value for SDS biopsy was > 6 (sensitivity =99.3%; specificity=100%). For the total the 980 patients, an SDS clinical > 3 had a sensitivity of 94.2%, specificity of 88.8%, and a likelihood ratio of 7.9. An SDS clinical score > 4 had a lower sensitivity of (76.9%) but higher specificity (98.6%). For sarcoidosis, the presence of specific clinical features, especially multi-organ involvement, can enhance the diagnostic certainty. The SDS scoring system quantitated the clinical features consistent with sarcoidosis. Copyright © 2018. Published by Elsevier Inc.

Dementia in Urban Black Outpatients: Initial Experience at the Emory Satellite Clinics.

ERIC Educational Resources Information Center

Auchus, Alexander P.

1997-01-01

Describes the demographic features and clinical diagnoses in a sample of 58 demented urban black outpatients. Results indicate that probable Alzheimer's disease was the most common cause of dementia whereas probable vascular dementia was uncommon. A multiple etiology dementia was identified in more than one-third of the patients. (RJM)

Upper extremity paraesthesia: clinical assessment and reasoning.

PubMed

Muscolino, Joseph E

2008-07-01

The art of clinical assessment involves an accurate determination of the cause(s) of a patient's symptoms. Given that a set of symptoms can be influenced by many contributing factors and features, assessment needs to differentially evaluate these. Accurate and appropriate treatment depends on differential assessment based on sound clinical reasoning. Many conditions derive from multiple causes demanding evaluation of as many etiological features as can be identified. The case review presented here involves a patient presenting with paraesthesia spreading into her right upper extremity. A complex history, involving her neck and contralateral upper extremity was assessed. The patient was found to have at least seven underlying, predisposing, and etiological, conditions capable of initiating, aggravating, or maintaining the presenting symptoms. Weighing the relative contributions of these often interacting features, and correlating this with the history, helped to identify a successful course of treatment.

Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

PubMed

Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

2017-08-08

Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

Innovative strategies for early clinical R&D.

PubMed

Butz, Robert F; Morelli, Gaetano

2008-01-01

Developments in translational medicine and regulatory initiatives associated with the FDA's Critical Path Initiative are creating new opportunities for innovation in early clinical R&D. The introduction of the exploratory IND process allows small, 'phase 0' clinical trials to be conducted prior to traditional phase I trials - sometimes requiring considerably less chemistry, manufacturing and controls, or preclinical support. Phase 0 clinical trials involving subtherapeutic, yet pharmacologically active, dose levels can provide an early demonstration of clinical proof of concept; such demonstration is of particular importance to small pharmaceutical and early-stage biotechnology companies. However, these opportunities for rapid entry into the clinic must be balanced by a consideration of the unique risks associated with first-in-human clinical trials, and by accounting for public concerns regarding drug safety in general. This feature review discusses how innovative clinical strategies can be used effectively in early drug development.

Comparison of Decision Assist and Clinical Judgment of Experts for Prediction of Lifesaving Interventions

DTIC Science & Technology

2015-03-01

min of pulse oximeter photopletysmograph waveforms and extracted features to predict LSIs. We compared this with clinical judgment of LSIs by...Curve (AUROC). We obtained clinical judgment of need for LSI from 405 expert clinicians in135 trauma patients. The pulse oximeter algorithm...15 min of pulse oximeter waveforms predicts the need for LSIs during initial trauma resuscitation as accurately as judgment of expert trauma

Fever as an initial manifestation of spondyloarthritis: A retrospective study.

PubMed

Byun, Se Jin; Bae, William Han; Jung, Seung Min; Lee, Sang-Won; Park, Yong-Beom; Song, Jason Jungsik

2017-01-01

We aimed to evaluate a wide spectrum of clinical features of adult patients with spondyloarthritis (SpA) whose initial manifestation was fever, using the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. We retrospectively collected the electronic medical records of hospitalized SpA patients who initially presented to the Severance Hospital (Seoul, Korea) with fever from January 2010 to May 2016. As a control group, we also recruited one-hundred consecutive patients who were diagnosed with SpA in our outpatient clinic. Clinical features and laboratory findings were compared in two patient groups. There were 26 patients who had fever as initial presentation of SpA (reactive arthritis 50%, undifferentiated SpA 26.9%, ankylosing spondylitis 15.4%, enteropathic arthritis 3.8%, psoriatic arthritis 3.8%). Peripheral SpA was more common in febrile SpA patients than in control SpA patients (65.4% vs 24.0%, p<0.001). Febrile SpA patients were less frequently HLA-B27 positive than control SpA patients (52.2% vs 77.0%, p<0.05). At baseline, systemic inflammatory markers were significantly higher in the febrile SpA patients (white blood cell count, 11.57 vs 7.81 cells/μL, p<0.001; erythrocyte sedimentation rate, 69.2 vs 41.0 mm/h, p<0.001; C-reactive protein, 109.6 vs 15.3 mg/L, p<0.001). The proportion of patients treated with systemic steroids was significantly higher in febrile SpA patients (57.7% vs. 11.0%, p<0.001). The proportion of patients who visited rheumatology specialty was significantly lower in febrile SpA patients than in control SpA patients (7.7% vs 59.0%, p<0.001). Various subgroups of SpA can be presented with fever as an initial manifestation. Febrile SpA patients demonstrated higher systemic inflammation and a lower chance to visit rheumatology in early stage. When evaluating febrile patients with any clinical features of SpA, clinicians are advised to consider performing SpA-focused evaluation including HLA-B27 or a simple sacroiliac joint radiograph.

Exploring cognitive integration of basic science and its effect on diagnostic reasoning in novices.

PubMed

Lisk, Kristina; Agur, Anne M R; Woods, Nicole N

2016-06-01

Integration of basic and clinical science knowledge is increasingly being recognized as important for practice in the health professions. The concept of 'cognitive integration' places emphasis on the value of basic science in providing critical connections to clinical signs and symptoms while accounting for the fact that clinicians may not spontaneously articulate their use of basic science knowledge in clinical reasoning. In this study we used a diagnostic justification test to explore the impact of integrated basic science instruction on novices' diagnostic reasoning process. Participants were allocated to an integrated basic science or clinical science training group. The integrated basic science group was taught the clinical features along with the underlying causal mechanisms of four musculoskeletal pathologies while the clinical science group was taught only the clinical features. Participants completed a diagnostic accuracy test immediately after initial learning, and one week later a diagnostic accuracy and justification test. The results showed that novices who learned the integrated causal mechanisms had superior diagnostic accuracy and better understanding of the relative importance of key clinical features. These findings further our understanding of cognitive integration by providing evidence of the specific changes in clinical reasoning when basic and clinical sciences are integrated during learning.

Healthcare-associated Pneumonia: Clinical Features and Retrospective Analysis Over 10 Years

PubMed Central

Qi, Fei; Zhang, Guo-Xin; She, Dan-Yang; Liang, Zhi-Xin; Wang, Ren-Tao; Yang, Zhen; Chen, Liang-An; Cui, Jun-Chang

2015-01-01

Background: Healthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis. Methods: Retrospective observational study among hospitalized patients with HCAP over 10 years. The primary outcome was 30-day all-cause hospital mortality after admission. Demographics (age, gender, clinical features, and comorbidities), dates of admission, discharge and/or death, hospitalization costs, microbiological results, chest imaging studies, and CURB-65 were analyzed. Antibiotics, admission to Intensive Care Unit (ICU), mechanical ventilation, and pneumonia prognosis were recorded. Patients were dichotomized based on CURB-65 (low- vs. high-risk). Results: Among 612 patients (mean age of 70.7 years), 88.4% had at least one comorbidity. Commonly detected pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Initial monotherapy with β-lactam antibiotics was the most common initial therapy (50%). Mean age, length of stay, hospitalization expenses, ICU admission, mechanical ventilation use, malignancies, and detection rate for P. aeruginosa, and Staphylococcus aureus were higher in the high-risk group compared with the low-risk group. CURB-65 ≥3, malignancies, and mechanical ventilation were associated with an increased mortality. Logistic regression analysis showed that cerebrovascular diseases and being bedridden were independent risk factors for HCAP. Conclusion: Initial treatment of HCAP with broad-spectrum antibiotics could be an appropriate approach. CURB-65 ≥3, malignancies, and mechanical ventilation may result in an increased mortality. PMID:26481734

Healthcare-associated Pneumonia: Clinical Features and Retrospective Analysis Over 10 Years.

PubMed

Qi, Fei; Zhang, Guo-Xin; She, Dan-Yang; Liang, Zhi-Xin; Wang, Ren-Tao; Yang, Zhen; Chen, Liang-An; Cui, Jun-Chang

2015-10-20

Healthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis. Retrospective observational study among hospitalized patients with HCAP over 10 years. The primary outcome was 30-day all-cause hospital mortality after admission. Demographics (age, gender, clinical features, and comorbidities), dates of admission, discharge and/or death, hospitalization costs, microbiological results, chest imaging studies, and CURB-65 were analyzed. Antibiotics, admission to Intensive Care Unit (ICU), mechanical ventilation, and pneumonia prognosis were recorded. Patients were dichotomized based on CURB-65 (low- vs. high-risk). Among 612 patients (mean age of 70.7 years), 88.4% had at least one comorbidity. Commonly detected pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Initial monotherapy with β-lactam antibiotics was the most common initial therapy (50%). Mean age, length of stay, hospitalization expenses, ICU admission, mechanical ventilation use, malignancies, and detection rate for P. aeruginosa, and Staphylococcus aureus were higher in the high-risk group compared with the low-risk group. CURB-65 ≥3, malignancies, and mechanical ventilation were associated with an increased mortality. Logistic regression analysis showed that cerebrovascular diseases and being bedridden were independent risk factors for HCAP. Initial treatment of HCAP with broad-spectrum antibiotics could be an appropriate approach. CURB-65 ≥3, malignancies, and mechanical ventilation may result in an increased mortality.

Clinicopathological correlates in HIV seropositive tuberculosis cases presenting with jaundice after initiating antiretroviral therapy with a structured review of the literature.

PubMed

Barr, David A; Ramdial, Pravistadevi K

2012-10-14

The development of jaundice after initiation of HAART in HIV-TB co-infected patients is a challenging presentation in resource constrained settings, and is often attributed to drug induced liver injury (DILI).Some investigators have described hepatic tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) as a cause of liver disease in patients initiating HAART, which could also cause jaundice. We report the clinical and histopathological features of five HIV-TB co-infected patients presenting with a syndrome of jaundice, tender hepatomegaly, bile canalicular enzyme rise and return of constitutional symptoms within 8 weeks of initiation of highly active antiretroviral therapy (HAART) for advanced HIV infection at a rural clinic in KwaZulu Natal, South Africa.All five patients had been diagnosed with tuberculosis infection prior to HAART initiation and were on antituberculous medication at time of developing jaundice. There was evidence of multiple aetiologies of liver injury in all patients. However, based on clinical course and pathological findings, predominant hepatic injury was thought to be drug induced in one case and hepatic tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) in the other four.In these later 4 patients, liver biopsy findings included necrotising and non-necrotising granulomatous inflammation in the lobules and portal tracts. The granulomas demonstrated - in addition to epithelioid histiocytes and Langhans giant cells - neutrophils, plasma cells and large numbers of lymphocytes, which are not features of a conventional untreated tuberculous response. In this high TB prevalent, low resource setting, TB-IRIS may be an important cause of jaundice post-HAART initiation. Clinicopathological correlation is essential for optimal diagnosis. Further multi-organ based histopathological studies in the context of immune reconstitution would be useful to clinicians in low resource settings dealing with this challenging presentation.

Clinical and imaging features in different inner border-zone infarct patterns.

PubMed

Wang, Yujie; Wang, Jian

2015-03-01

The clinical and imaging features of different inner border-zone infarct patterns, corona radiata (CR) and centrum semiovale (CSO), is not quiet clear. Both are mostly reported together in previous studies. We intended to observe their clinical and imaging features. We observed 83 patients-47 cases with CR infarct lesion pattern and 36 cases with CSO. The lesion patterns were determined by diffusion-weighted imaging. Basic, clinical and radiologic features were compared between the patients with CR and CSO infarct lesion patterns. There was no significant difference between CR and CSO infarct patterns in terms of risk factors. However, patients with CR infarct had a higher initial National Institutes of Health Stroke Scale (NIHSS) score at admission (5.2 ± 2.3) than with CSO (3.9 ± 2.0, p = 0.009). Early clinical deterioration (OR, 2.42; 95% CI, 1.12-5.21; p = 0.024) and middle cerebral artery (MCA) stenosis (OR, 10.31; 95% CI, 3.30-32.19; p < 0.0001) were independently associated with the CR infarct lesion pattern. Partial infarct lesion shape (OR, 5.95; 95% CI, 1.40-25.33; p = 0.016) and internal carotid artery (ICA) stenosis (OR, 5.28; 95% CI, 1.92-14.51; p = 0.001) were independently correlated with the CSO infarct lesion pattern. Although CR and CSO infarct patterns might share common etiology and mechanisms, their clinical and imaging features are different.

Variations in the implementation and characteristics of chiropractic services in VA.

PubMed

Lisi, Anthony J; Khorsan, Raheleh; Smith, Monica M; Mittman, Brian S

2014-12-01

In 2004, the US Department of Veterans Affairs expanded its delivery of chiropractic care by establishing onsite chiropractic clinics at select facilities across the country. Systematic information regarding the planning and implementation of these clinics and describing their features and performance is lacking. To document the planning, implementation, key features and performance of VA chiropractic clinics, and to identify variations and their underlying causes and key consequences as well as their implications for policy, practice, and research on the introduction of new clinical services into integrated health care delivery systems. Comparative case study of 7 clinics involving site visit-based and telephone-based interviews with 118 key stakeholders, including VA clinicians, clinical leaders and administrative staff, and selected external stakeholders, as well as reviews of key documents and administrative data on clinic performance and service delivery. Interviews were recorded, transcribed, and analyzed using a mixed inductive (exploratory) and deductive approach. Interview data revealed considerable variations in clinic planning and implementation processes and clinic features, as well as perceptions of clinic performance and quality. Administrative data showed high variation in patterns of clinic patient care volume over time. A facility's initial willingness to establish a chiropractic clinic, along with a higher degree of perceived evidence-based and collegial attributes of the facility chiropractor, emerged as key factors associated with higher and more consistent delivery of chiropractic services and higher perceived quality of those services.

The More the Merrier? Working Towards Multidisciplinary Management of Obstructive Sleep Apnea and Comorbid Insomnia

PubMed Central

Ong, Jason C.; Crisostomo, M. Isabel

2013-01-01

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder that is associated with negative cardiovascular consequences and adverse events from excessive daytime sleepiness. Insomnia is the inability to initiate or maintain sleep accompanied by daytime dysfunction. OSA and insomnia co-occur at a high rate, and such patients appear to have distinct clinical features of both disorders. Although empirically supported treatments are now available for OSA and insomnia independently, there are currently no standards or guidelines for how to combine or initiate these treatments for patients who suffer from both sleep disorders. Our goal was to review the literature on current diagnostic considerations, clinical features, pathophysiology, and treatment approaches for patients with OSA and comorbid insomnia. In particular, the potential benefits and challenges of using a multidisciplinary treatment model are discussed, including a research strategy that could inform implementation of pulmonary and behavioral sleep medicine treatments. The research, clinical, and policy implications of treating both OSA and insomnia are discussed with the hope that further activity will establish standards or guidelines for patients with OSA and insomnia. PMID:23382086

Do Orthopaedic Oncologists Agree on the Diagnosis and Treatment of Cartilage Tumors of the Appendicular Skeleton?

PubMed

Zamora, Tomas; Urrutia, Julio; Schweitzer, Daniel; Amenabar, Pedro Pablo; Botello, Eduardo

2017-09-01

Distinguishing a benign enchondroma from a low-grade chondrosarcoma is a common diagnostic challenge for orthopaedic oncologists. Low interrater agreement has been observed for the diagnosis of cartilaginous neoplasms among radiologists and pathologists, but, to our knowledge, no study has evaluated inter- and intraobserver agreement among orthopaedic oncologists grading these lesions using initial clinical and imaging information. Determining such agreement is important since it reflects the certainty in the diagnosis by orthopaedic oncologists. Agreement also is important as it will guide future treatment and prognosis, considering that there is no gold standard for diagnosis of these lesions. (1) to determine inter- and intraobserver agreement among a multinational panel of expert orthopaedic oncologists in diagnosing cartilaginous neoplasms based on their assessment of clinical symptoms and imaging at diagnosis. (2) To describe the most important clinical and imaging features that experts use during the initial diagnostic process. (3) To determine interobserver agreement for proposed initial treatment strategies for cartilaginous neoplasms by this panel of evaluators. Thirty-nine patients with intramedullary cartilaginous neoplasms of the appendicular skeleton of various histopathologic grades were selected and classified as having benign, low-grade malignant, or intermediate- or high-grade malignant neoplasms by 10 experienced orthopaedic oncologists based on clinical and imaging information. Additionally, they chose the three most important clinical or imaging features for the diagnosis of these neoplasms, and they proposed a treatment strategy for each patient. The Kappa coefficient (κ) was used to determine inter- and intraobserver agreement. Inter- and intraobserver agreements were only fair to good, κ = 0.44(95% CI, 0.41-0.48) and κ = 0.62 (95% CI, 0.52-0.72), respectively. The three factors most frequently identified as helpful in making the diagnosis by our panel were cortical involvement in 65% of evaluations (253/390), neoplasm size in 51% (198/390), and pain in 50% (194/390). The interobserver agreement for the proposed initial treatment strategy after diagnosis was poor (κ = 0.21; 95% CI, 0.18-0.24). This study showed barely fair interobserver and fair to good intraobserver agreement for grading of intramedullary cartilaginous neoplasms by orthopaedic oncologists using initial clinical and imaging findings. These results reflect the insufficient guidance interpreting clinical and imaging features, and the limitations of the systems we use today when making these diagnoses. In the same way, they generate concern for the implications that this may have on different treatment strategies and the future prognosis of our patients. Future studies should build on these observations and focus on clarifying our criteria of diagnosis so that treatment recommendations are standardized regardless of the treating institution or oncologist. Level III, diagnostic study.

Hidden flexion injury of the cervical spine.

PubMed

Webb, J K; Broughton, R B; McSweeney, T; Park, W M

1976-08-01

This paper describes seven patients who developed late vertebral deformity after flexion injuries of the cervical spine. In four the clinical and radiological features were subtle and because the patients walked into an emergency department the severity of the injury was not initially appreciated. Certain specific clinical and radiological features of flexion injury are described and emphasis is placed on the importance of correct management. A radiological tetrad is described which should alert the surgeon to the possibility of damage to the posterior interspinous complex of the cervical spine and so lead to further radiological investigations. Despite the frequency of flexion injuries the alarming complications described in this paper are rare.

Improved Diagnostic Multimodal Biomarkers for Alzheimer's Disease and Mild Cognitive Impairment

PubMed Central

Martínez-Torteya, Antonio; Treviño, Víctor; Tamez-Peña, José G.

2015-01-01

The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) is very important for treatment research and patient care purposes. Few biomarkers are currently considered in clinical settings, and their use is still optional. The objective of this work was to determine whether multimodal and nonpreviously AD associated features could improve the classification accuracy between AD, MCI, and healthy controls, which may impact future AD biomarkers. For this, Alzheimer's Disease Neuroimaging Initiative database was mined for case-control candidates. At least 652 baseline features extracted from MRI and PET analyses, biological samples, and clinical data up to February 2014 were used. A feature selection methodology that includes a genetic algorithm search coupled to a logistic regression classifier and forward and backward selection strategies was used to explore combinations of features. This generated diagnostic models with sizes ranging from 3 to 8, including well documented AD biomarkers, as well as unexplored image, biochemical, and clinical features. Accuracies of 0.85, 0.79, and 0.80 were achieved for HC-AD, HC-MCI, and MCI-AD classifications, respectively, when evaluated using a blind test set. In conclusion, a set of features provided additional and independent information to well-established AD biomarkers, aiding in the classification of MCI and AD. PMID:26106620

Conjunctival papilloma: features and outcomes based on age at initial examination.

PubMed

Kaliki, Swathi; Arepalli, Sruthi; Shields, Carol L; Klein, Kendra; Sun, Hong; Hysenj, Eralda; Lally, Sara E; Shields, Jerry A

2013-05-01

Conjunctival papilloma is a benign epithelial tumor occurring in both children and adults with varying clinical features and outcomes. In this article, we describe our experience regarding the difference in the clinical features and outcomes of conjunctival papilloma based on age at initial examination. To evaluate the clinical features, treatment, and outcomes in patients with conjunctival papilloma based on age at initial examination. Retrospective study. Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania. Ten children and adolescents (aged ≤20 years) and 63 adults (aged >20 years) with conjunctival papilloma. Excisional biopsy, cryotherapy, oral cimetidine, topical or injection interferon alfa-2b, and photodynamic therapy. Tumor response. A comparison of conjunctival papillomas between age groups revealed significant differences in the mean number of tumors per eye (children and adolescents vs adults, 2 vs 1; P = .05), tumor basal dimension (8 vs 6 mm; P = .05), and associated feeder vessels (20% vs 47%; P = .05). Primary treatment included sole treatment with oral cimetidine (15% vs 5%), topical interferon alfa-2b (0% vs 1%), cryotherapy (0% vs 3%), photodynamic therapy (0% vs 1%), excisional biopsy and cryotherapy (38% vs 65%), excisional biopsy and cryotherapy with adjuvant oral cimetidine (8% vs 9%), and excisional biopsy and cryotherapy with adjuvant topical or injection interferon alfa-2b (38% vs 15%). Significant differences in age groups in treatment outcome during the follow-up period (mean, 24 vs 38 months) included complete regression with single treatment (38% vs 95%; P < .01) and tumor recurrence (15% vs 1%; P = .05). Conjunctival papillomas are larger and more likely to be multiple in children and adolescents than in adults. Excisional biopsy and cryotherapy with or without adjuvant oral cimetidine and/or topical interferon alfa-2b provide satisfactory tumor control. Papilloma recurrence is more common in children and adolescents than in adults.

The Relative Importance of Family History, Gender, Mode of Onset, and Age at Onsetin Predicting Clinical Features of First-Episode Psychotic Disorders.

PubMed

Compton, Michael T; Berez, Chantal; Walker, Elaine F

Family history of psychosis, gender, mode of onset, and age at onset are considered prognostic factors important to clinicians evaluating first-episode psychosis; yet, clinicians have little guidance as to how these four factors differentially predict early-course substance abuse, symptomatology, and functioning. We conducted a "head-to-head comparison" of these four factors regarding their associations with key clinical features at initial hospitalization. We also assessed potential interactions between gender and family history with regard to age at onset of psychosis and symptom severity. Consecutively admitted first-episode patients (n=334) were evaluated in two studies that rigorously assessed a number of early-course variables. Associations among variables of interest were examined using Pearson correlations, χ 2 tests, Student's t-tests, and 2×2 factorial analyses of variance. Substance (nicotine, alcohol, and cannabis) abuse and positive symptom severity were predicted only by male gender. Negative symptom severity and global functioning impairments were predicted by earlier age at onset of psychosis. General psychopathology symptom severity was predicted by both mode of onset and age at onset. Interaction effects were not observed with regard to gender and family history in predicting age at onset or symptom severity. The four prognostic features have differential associations with substance abuse, domains of symptom severity, and global functioning. Gender and age at onset of psychosis appear to be more predictive of clinical features at the time of initial evaluation (and thus presumably longer term outcomes) than the presence of a family history of psychosis and a more gradual mode of onset.

Serum carcinoembryonic antigen levels before initial treatment are associated with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.

PubMed

Wang, Wen-Tao; Li, Yin; Ma, Jie; Chen, Xiao-Bing; Qin, Jian-Jun

2014-01-01

Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5 ng/ml seemed to be higher than patients with a concentration over 5 ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

Clinical prediction of Gardnerella vaginalis in general practice

PubMed Central

O'Dowd, T.C.; West, R.R.

1987-01-01

In a study of 162 women with vaginal symptoms the clinical features of increased discharge, yellow discharge, 'high cheese' odour and pH greater than 5 were statistically strongly associated with the presence of Gardnerella vaginalis, confirmed by microbiological culture. The sensitivities and specificities of these clinical tests, although not as high as those of previously described sideroom tests using the amine test and microscopy for 'clue cells' nevertheless allow the clinician to predict G. vaginalis reliably and initiate treatment at first consultation. PMID:3499508

Diagnosis of systemic lupus erythematosus in an unusual presentation: what a primary care physician should know.

PubMed

Pramanik, Bimalendu

2014-01-01

Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease affecting millions of people worldwide. It can affect any organ systems of the body. However, all systems may not be involved initially rather than they may be affected gradually, sometimes over years. Diagnosis depends on characteristic clinical features and laboratory test results. Some features such as skin rash, joint symptoms and oral ulcers are common in SLE. But initial presentation of many patients is unusual because either they do not have these common features of the disease or the presentation mimics other illnesses. As a result, delayed diagnosis and misdiagnosis are common. Therefore, high index of initial suspicion of SLE is critical. In clinical practice, SLE should be suspected in any patient presenting with an unexplained disease process involving two or more organ systems. To make a diagnosis in an unusual presentation, thorough clinical evaluation with details history of both present and past illnesses as well as laboratory tests for SLE should be performed. Usually primary-care physicians first evaluate SLE patients; but there is no single article, where all the information on when to suspect SLE in an unusual presentation, is available in an integrated form. In this article, a list of conditions, when SLE should be suspected in an unusual presentation, has been given and some relatively common areas with diagnostic challenges of SLE have been briefly described. To prepare this manuscript, most articles have been identified through 'Pubmed' search using keywords-atypical/ unusual presentation of SLE, case reports on SLE, gastrointestinal manifestations of SLE, neuropsychiatric SLE, diagnostic challenges with SLE, etc. Selected most articles are from currently medline-indexed journals.

The diagnosis of idiopathic pulmonary fibrosis: current and future approaches

PubMed Central

Martinez, Fernando J; Chisholm, Alison; Collard, Harold R; Flaherty, Kevin R; Myers, Jeffrey; Raghu, Ganesh; Walsh, Simon LF; White, Eric S; Richeldi, Luca

2017-01-01

With the recent development of two effective treatments for patients with idiopathic pulmonary fibrosis, an accurate diagnosis is crucial. The traditional approach to diagnosis emphasises the importance of thorough clinical and laboratory evaluations to exclude secondary causes of disease. High-resolution CT is a critical initial diagnostic test and acts as a tool to identify patients who should undergo surgical lung biopsy to secure a definitive histological diagnosis of usual interstitial pneumonia pattern. This diagnostic approach faces several challenges. Many patients with suspected idiopathic pulmonary fibrosis present with atypical high-resolution CT characteristics but are unfit for surgical lung biopsy, therefore preventing a confident diagnosis. The state of the art suggests an iterative, multidisciplinary process that incorporates available clinical, laboratory, imaging, and histological features. Recent research has explored genomic techniques to molecularly phenotype patients with interstitial lung disease. In the future, clinicians will probably use blood-specific or lung-specific molecular markers in combination with other clinical, physiological, and imaging features to enhance diagnostic efforts, refine prognostic recommendations, and influence the initial or subsequent treatment options. There is an urgent and increasing need for well designed, large, prospective studies measuring the effect of different diagnostic approaches. Ultimately, this will help to inform the development of guidelines and tailor clinical practice for the benefit of patients. PMID:27932290

Characteristics of U.S. Veteran Patients with Major Depressive Disorder who require "next-step" treatments: A VAST-D report.

PubMed

Zisook, Sidney; Tal, Ilanit; Weingart, Kimberly; Hicks, Paul; Davis, Lori L; Chen, Peijun; Yoon, Jean; Johnson, Gary R; Vertrees, Julia E; Rao, Sanjai; Pilkinton, Patricia D; Wilcox, James A; Sapra, Mamta; Iranmanesh, Ali; Huang, Grant D; Mohamed, Somaia

2016-12-01

Finding effective and lasting treatments for patients with Major Depressive Disorder (MDD) that fail to respond optimally to initial standard treatment is a critical public health imperative. Understanding the nature and characteristics of patients prior to initiating "next-step" treatment is an important component of identifying which specific treatments are best suited for individual patients. We describe clinical features and demographic characteristics of a sample of Veterans who enrolled in a "next-step" clinical trial after failing to achieve an optimal outcome from at least one well-delivered antidepressant trial. 1522 Veteran outpatients with nonpsychotic MDD completed assessments prior to being randomized to study treatment. Data is summarized and presented in terms of demographic, social, historical and clinical features and compared to a similar, non-Veteran sample. Participants were largely male and white, with about half unmarried and half unemployed. They were moderately severely depressed, with about one-third reporting recent suicidal ideation. More than half had chronic and/or recurrent depression. General medical and psychiatric comorbidities were highly prevalent, particularly PTSD. Many had histories of childhood adversity and bereavement. Participants were impaired in multiple domains of their lives and had negative self-worth. These results may not be generalizable to females, and some characteristics may be specific to Veterans of US military service. There was insufficient data on age of clinical onset and depression subtypes, and three novel measures were not psychometrically validated. Characterizing VAST-D participants provides important information to help clinicians understand features that may optimize "next-step" MDD treatments. Published by Elsevier B.V.

Adult Orbital and Adnexal Xanthogranulomatous Disease.

PubMed

Davies, Michael J; Whitehead, Kevin; Quagliotto, Gary; Wood, Dominic; Patheja, Rajan S; Sullivan, Timothy J

2017-01-01

Adult xanthogranulomatous disease of the orbit and ocular adnexa is a rare disease that can cause serious morbidity and mortality. Ophthalmologists are commonly the first clinicians to come in contact with affected patients and an understanding of the clinical features is essential. We present a retrospective case series of patients seen in the oculoplastic unit of a large tertiary referral hospital over a 20-year period. The clinical files of 7 patients with adult xanthogranulomatous disease of the orbit and ocular adnexa were reviewed. Clinical, radiological, histopathological, and immunohistochemical findings were examined. Periocular clinical features included cutaneous xanthogranulomatous lesions, decreased visual acuity, proptosis, diplopia, skin ulceration, cicatricial ectropion, and mechanical ptosis. Systemic features included adult-onset asthma, disseminated xanthogranulomatous lesions with long bone involvement, and hematological disturbances such as monoclonal gammopathy and lymphoplasmacytic lymphoma. Lipid-laden macrophages and Touton multinucleated giant cells were histological hallmarks in all subtypes. Most lesions were strongly CD8 positive on immunohistochemistry. Radiologically, the lesions were diffuse and infiltrative in nature. Various treatments were employed with varying success including surgical excision, systemic and intralesional corticosteroids, other immunosuppressants, and systemic chemotherapy. Adult xanthogranulomatous disease of the orbit and ocular adnexa, although rare, may be sight or life threatening. Recognition by the ophthalmologist is critical as periocular features often constitute the initial presentation. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Plantar keloids: diagnostic and therapeutic issues in six patients.

PubMed

Vanhaecke, C; Hickman, G; Cavelier-Balloy, B; Masson, V; Duron, J-B; Gorj, M; May, P; Schneider, P; Vilmer, C; Bagot, M; Battistella, M; Petit, A

2015-07-01

Keloids are benign fibro-proliferative skin lesions that very rarely occur on the soles. Because of their rarity, the diagnosis of plantar keloids can be difficult. We describe the clinical and histopathological characteristics of eight plantar keloids. All patients presenting with plantar keloids between 2005 and 2012 in our Dermatology unit were retrospectively included. Diagnosis was definitely established by re-reading of pathological slides in all cases. Clinical characteristics, histopathological features, treatments given and their results were collected. Six patients were included. Five patients had a single plantar keloid and one had three lesions. They all were of African descent. Only one patient remembered of a previous injury at the site of the keloid. Three patients presented with associated extra-plantar keloids. In four patients, the diagnosis of keloid was not initially suspected clinically or histologically. Re-reading of the clinical photographs showed that the eight plantar keloids shared common morphological features, leading to a distinctive clinical picture, defined by a hardened lesion of rounded or polycyclic shape, with a pink surface crossed by keratotic furrows and the presence of a hyperkeratotic rim. Concerning pathological features, typical hyalinized collagen can be missing and deep fibrosis should not rule out the diagnosis of keloid. Intralesional injection of triamcinolone acetonide and orthopaedic shoes were useful. All patients who had surgical excision presented recurrence. The knowledge of the clinical features of plantar keloids is helpful to the diagnosis. There is no well-established treatment, but supportive measures are important. © 2014 European Academy of Dermatology and Venereology.

Clinics in diagnostic imaging (179). Severe rhabdomyolysis complicated by myonecrosis.

PubMed

Kok, Shi Xian Shawn; Tan, Tien Jin

2017-08-01

A 32-year-old man presented to the emergency department with severe right lower limb pain and swelling of three days' duration. He had multiple prior admissions for recurrent seizures and suicide attempts. Markedly elevated serum creatine kinase levels and urine myoglobinuria were consistent with a diagnosis of rhabdomyolysis. Initial magnetic resonance imaging of the right lower limb revealed diffuse muscle oedema and features of myositis in the gluteal muscles and the adductor, anterior and posterior compartments of the thigh. Follow-up magnetic resonance imaging performed 11 days later showed interval development of areas of myonecrosis and haemorrhage. The causes, clinical presentation and imaging features of rhabdomyolysis are discussed. Copyright: © Singapore Medical Association.

Multivariate Protein Signatures of Pre-Clinical Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Plasma Proteome Dataset

PubMed Central

Johnstone, Daniel; Milward, Elizabeth A.; Berretta, Regina; Moscato, Pablo

2012-01-01

Background Recent Alzheimer's disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. Methods and Findings We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10−13). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. Conclusions Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of plasma biomarkers for pre-clinical AD. While studies of independent test sets are required to validate the signatures, these analyses provide a starting point for developing a cost-effective and minimally invasive test capable of diagnosing AD in its pre-clinical stages. PMID:22485168

Hemophagocytic syndrome as the initial manifestation of systemic lupus erythematosus.

PubMed

Egües Dubuc, César Antonio; Uriarte Ecenarro, Miren; Meneses Villalba, Carlos; Aldasoro Cáceres, Vicente; Hernando Rubio, Iñaki; Belzunegui Otano, Joaquín

2014-01-01

Hemophagocytic syndrome (HS) occurs in autoimmune diseases and belongs to the hemophagocytic lymphohistiocytosis group of diseases. This paper describes the features of 2 patients with systemic lupus erythematosus (SLE) who presented HS as the initial clinical manifestation. Both patients had prolonged fever not associated to an infectious process and did not respond to broad-spectrum antibiotics. The diagnosis of HS secondary to SLE is complicated, because it has some features in common, but HS is characterized by hyperferritinemia, hipofibrinogemia, hypertriglyceridemia and a decrease in the erythrocyte sedimentation rate, unlike SLE. HS treatment when associated to SLE is not well established, but steroids and/or immunoglobulins are effective as the initial treatment, and in refractory cases, cyclosporine or cyclophosphamide may be associated. HS can be the initial manifestation of SLE and should be suspected in patients with organ enlargement, cytopenias, clotting disorders, liver disorders and prolonged fever unresponsive to antibiotics. Anakinra may be a treatment option in adult HS associated to SLE. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome.

PubMed

Olson, Heather E; Tambunan, Dimira; LaCoursiere, Christopher; Goldenberg, Marti; Pinsky, Rebecca; Martin, Emilie; Ho, Eugenia; Khwaja, Omar; Kaufmann, Walter E; Poduri, Annapurna

2015-09-01

Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks. © 2015 Wiley Periodicals, Inc.

Mutations in Epilepsy and Intellectual Disability Genes in Patients with Features of Rett Syndrome

PubMed Central

Olson, Heather E.; Tambunan, Dimira; LaCoursiere, Christopher; Goldenberg, Marti; Pinsky, Rebecca; Martin, Emilie; Ho, Eugenia; Khwaja, Omar; Kaufmann, Walter E.; Poduri, Annapurna

2017-01-01

Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks. PMID:25914188

Features of computerized clinical decision support systems supportive of nursing practice: a literature review.

PubMed

Lee, Seonah

2013-10-01

This study aimed to organize the system features of decision support technologies targeted at nursing practice into assessment, problem identification, care plans, implementation, and outcome evaluation. It also aimed to identify the range of the five stage-related sequential decision supports that computerized clinical decision support systems provided. MEDLINE, CINAHL, and EMBASE were searched. A total of 27 studies were reviewed. The system features collected represented the characteristics of each category from patient assessment to outcome evaluation. Several features were common across the reviewed systems. For the sequential decision support, all of the reviewed systems provided decision support in sequence for patient assessment and care plans. Fewer than half of the systems included problem identification. There were only three systems operating in an implementation stage and four systems in outcome evaluation. Consequently, the key steps for sequential decision support functions were initial patient assessment, problem identification, care plan, and outcome evaluation. Providing decision support in such a full scope will effectively help nurses' clinical decision making. By organizing the system features, a comprehensive picture of nursing practice-oriented computerized decision support systems was obtained; however, the development of a guideline for better systems should go beyond the scope of a literature review.

A Method for Extracting Suspected Parotid Lesions in CT Images using Feature-based Segmentation and Active Contours based on Stationary Wavelet Transform

NASA Astrophysics Data System (ADS)

Wu, T. Y.; Lin, S. F.

2013-10-01

Automatic suspected lesion extraction is an important application in computer-aided diagnosis (CAD). In this paper, we propose a method to automatically extract the suspected parotid regions for clinical evaluation in head and neck CT images. The suspected lesion tissues in low contrast tissue regions can be localized with feature-based segmentation (FBS) based on local texture features, and can be delineated with accuracy by modified active contour models (ACM). At first, stationary wavelet transform (SWT) is introduced. The derived wavelet coefficients are applied to derive the local features for FBS, and to generate enhanced energy maps for ACM computation. Geometric shape features (GSFs) are proposed to analyze each soft tissue region segmented by FBS; the regions with higher similarity GSFs with the lesions are extracted and the information is also applied as the initial conditions for fine delineation computation. Consequently, the suspected lesions can be automatically localized and accurately delineated for aiding clinical diagnosis. The performance of the proposed method is evaluated by comparing with the results outlined by clinical experts. The experiments on 20 pathological CT data sets show that the true-positive (TP) rate on recognizing parotid lesions is about 94%, and the dimension accuracy of delineation results can also approach over 93%.

A fully covered self-expandable metal stent with antimigration features for benign biliary strictures: a prospective, multicenter cohort study.

PubMed

Walter, Daisy; Laleman, Wim; Jansen, Jeroen M; van Milligen de Wit, A W M; Weusten, Bas L; van Boeckel, Petra G; Hirdes, Meike M; Vleggaar, Frank P; Siersema, Peter D

2015-05-01

Self-expandable metal stents (SEMSs) are increasingly used for the treatment of benign biliary strictures (BBSs). A new fully covered SEMS (FCSEMS) with flared ends and high conformability was designed to prevent migration of the stent. To evaluate the efficacy of a novel FCSEMS with antimigration features. Prospective cohort study. Five hospitals in the Netherlands and Belgium. Consecutive patients with BBS. FCSEMS placement for 3 months. Initial and long term clinical success, stent migration rate and safety. Thirty-eight patients (24 men; mean age, 53 ± 16 years) were included. Stent placement was technically successful in 37 patients (97%). Two patients died of an unrelated cause before stent removal, and no data on these patients were available on stricture resolution. Initial clinical success was achieved in 28 of 35 patients (80%). During follow-up after stent removal, a symptomatic recurrent stricture developed in 6 of 28 patients (21%). Overall, the long-term clinical success rate was 63% (22 of 35 patients). Stent migration occurred in 11 of 35 patients (31%), including 5 symptomatic (14%) and 6 asymptomatic (17%) migrations. In total, 11 serious adverse events occurred in 10 patients (29%), with cholangitis (n = 5) being most common. Nonrandomized study design. Good initial clinical success was achieved after placement of this novel FCSEMS, but stricture recurrence was in the upper range compared with other FCSEMSs. The antimigration design could not prevent migration in a significant number of patients with a persisting stricture. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

[Severity classification of chronic obstructive pulmonary disease based on deep learning].

PubMed

Ying, Jun; Yang, Ceyuan; Li, Quanzheng; Xue, Wanguo; Li, Tanshi; Cao, Wenzhe

2017-12-01

In this paper, a deep learning method has been raised to build an automatic classification algorithm of severity of chronic obstructive pulmonary disease. Large sample clinical data as input feature were analyzed for their weights in classification. Through feature selection, model training, parameter optimization and model testing, a classification prediction model based on deep belief network was built to predict severity classification criteria raised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We get accuracy over 90% in prediction for two different standardized versions of severity criteria raised in 2007 and 2011 respectively. Moreover, we also got the contribution ranking of different input features through analyzing the model coefficient matrix and confirmed that there was a certain degree of agreement between the more contributive input features and the clinical diagnostic knowledge. The validity of the deep belief network model was proved by this result. This study provides an effective solution for the application of deep learning method in automatic diagnostic decision making.

Network Analysis of Associations between Serum Interferon Alpha Activity, Autoantibodies, and Clinical Features in Systemic Lupus Erythematosus

PubMed Central

Weckerle, Corinna E.; Franek, Beverly S.; Kelly, Jennifer A.; Kumabe, Marissa; Mikolaitis, Rachel A.; Green, Stephanie L.; Utset, Tammy O.; Jolly, Meenakshi; James, Judith A.; Harley, John B.; Niewold, Timothy B.

2010-01-01

Background Interferon-alpha (IFN-α) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFN-α levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. We used multivariate and network analyses to detect associations between clinical and serologic disease manifestations and serum IFN-α activity in a large diverse SLE cohort. Methods 1089 SLE patients were studied (387 African-American, 186 Hispanic-American, and 516 European-American). Presence or absence of ACR clinical criteria for SLE, autoantibodies, and serum IFN-α activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each background separately to establish the network of associations between variables that were independently significant following Bonferroni correction. Results In all ancestral backgrounds, high IFN-α activity was associated with anti-Ro and anti-dsDNA antibodies (p-values 4.6×10−18 and 2.9 × 10−16 respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFN-α activity (p≤6.7×10−4). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared by more than one ancestral background. Associations between clinical criteria were different in different ancestral backgrounds, while autoantibody-IFN-α relationships were similar across backgrounds. IFN-α activity and autoantibodies were not associated with ACR clinical features in multivariate models. Conclusions Serum IFN-α activity was strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFN-α may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations. PMID:21162028

Extracorporeal photopheresis: Review of technical aspects.

PubMed

Arora, Satyam; Setia, Rasika

2017-01-01

Extracorporeal photochemotherapy (ECP) is considered as an immune modulating therapy majorly targeting the T cells of the Immune system. ECP induces an anti-inflammatory condition with tolerogenic responses without inducing a global immunosuppression state which is a typical feature of other therapeutic options such as steroids. Clinical indication of ECP has grown over time since its initial applications. Our review discusses the technical aspects of the concept of photopheresis with the available methods for its clinical applications.

[Frontal fibrosing alopecia: case series and literature review].

PubMed

Tinoco-Fragoso, Fátima; Domínguez-Cherit, Judith; Méndez-Flores, Silvia

2017-01-01

Frontal fibrosing alopecia is a disease characterized by a symmetric and progressive loss of hair in the fronto-temporal and fronto-parietal lines that generally affects postmenopausal women. It is considered a variant of lichen planus pilaris for its clinical and histopathological features; although, its etiopathology is still unknown. In this report, we analyzed 4 cases of this disease and we discussed its clinical and histopathological characteristics, as well as their course after initiating treatment.

Supporting open access to clinical trial data for researchers: The Duke Clinical Research Institute-Bristol-Myers Squibb Supporting Open Access to Researchers Initiative.

PubMed

Pencina, Michael J; Louzao, Darcy M; McCourt, Brian J; Adams, Monique R; Tayyabkhan, Rehbar H; Ronco, Peter; Peterson, Eric D

2016-02-01

There are growing calls for sponsors to increase transparency by providing access to clinical trial data. In response, Bristol-Myers Squibb and the Duke Clinical Research Institute have collaborated on a new initiative, Supporting Open Access to Researchers. The aim is to facilitate open sharing of Bristol-Myers Squibb trial data with interested researchers. Key features of the Supporting Open Access to Researchers data sharing model include an independent review committee that ensures expert consideration of each proposal, stringent data deidentification/anonymization and protection of patient privacy, requirement of prespecified statistical analysis plans, and independent review of manuscripts before submission for publication. We believe that these approaches will promote open science by allowing investigators to verify trial results as well as to pursue interesting secondary uses of trial data without compromising scientific integrity. Copyright © 2015 Elsevier Inc. All rights reserved.

Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations.

PubMed

Paisán-Ruiz, Coro; Guevara, Rocio; Federoff, Monica; Hanagasi, Hasmet; Sina, Fardaz; Elahi, Elahe; Schneider, Susanne A; Schwingenschuh, Petra; Bajaj, Nin; Emre, Murat; Singleton, Andrew B; Hardy, John; Bhatia, Kailash P; Brandner, Sebastian; Lees, Andrew J; Houlden, Henry

2010-09-15

Seven autosomal recessive genes associated with juvenile and young-onset Levodopa-responsive parkinsonism have been identified. Mutations in PRKN, DJ-1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor-Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden-Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor-Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido-pyramidal syndrome. © 2010 Movement Disorder Society.

Early-Onset L-dopa-Responsive Parkinsonism with Pyramidal Signs Due to ATP13A2, PLA2G6, FBXO7 and Spatacsin Mutations

PubMed Central

Paisán-Ruiz, Coro; Guevara, Rocio; Federoff, Monica; Hanagasi, Hasmet; Sina, Fardaz; Elahi, Elahe; Schneider, Susanne A.; Schwingenschuh, Petra; Bajaj, Nin; Emre, Murat; Singleton, Andrew B.; Hardy, John; Bhatia, Kailash P.; Brandner, Sebastian; Lees, Andrew J.; Houlden, Henry

2018-01-01

Seven autosomal recessive genes associated with juvenile and young-onset Levodopa-responsive parkinsonism have been identified. Mutations in PRKN, DJ-1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor-Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson’s disease including supranu-clear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden-Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor-Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido-pyramidal syndrome. 3 2010 Movement Disorder Society PMID:20669327

Clinicopathological correlates in HIV seropositive tuberculosis cases presenting with jaundice after initiating antiretroviral therapy with a structured review of the literature

PubMed Central

2012-01-01

Background The development of jaundice after initiation of HAART in HIV-TB co-infected patients is a challenging presentation in resource constrained settings, and is often attributed to drug induced liver injury (DILI).Some investigators have described hepatic tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) as a cause of liver disease in patients initiating HAART, which could also cause jaundice. Case presentations We report the clinical and histopathological features of five HIV-TB co-infected patients presenting with a syndrome of jaundice, tender hepatomegaly, bile canalicular enzyme rise and return of constitutional symptoms within 8 weeks of initiation of highly active antiretroviral therapy (HAART) for advanced HIV infection at a rural clinic in KwaZulu Natal, South Africa. All five patients had been diagnosed with tuberculosis infection prior to HAART initiation and were on antituberculous medication at time of developing jaundice. There was evidence of multiple aetiologies of liver injury in all patients. However, based on clinical course and pathological findings, predominant hepatic injury was thought to be drug induced in one case and hepatic tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) in the other four. In these later 4 patients, liver biopsy findings included necrotising and non-necrotising granulomatous inflammation in the lobules and portal tracts. The granulomas demonstrated – in addition to epithelioid histiocytes and Langhans giant cells – neutrophils, plasma cells and large numbers of lymphocytes, which are not features of a conventional untreated tuberculous response. Conclusion In this high TB prevalent, low resource setting, TB-IRIS may be an important cause of jaundice post-HAART initiation. Clinicopathological correlation is essential for optimal diagnosis. Further multi-organ based histopathological studies in the context of immune reconstitution would be useful to clinicians in low resource settings dealing with this challenging presentation. PMID:23061403

Crossed asymmetry in Russell-Silver syndrome.

PubMed Central

Qazi, Q H; Kassner, E G; Ganapathy, C

1977-01-01

Since the initial report by Silver et al (1953), more than 50 examples of the Russell-Silver syndrome have been reported. Unilateral congenital asymmetry of the extremities has been considered one of the major features of this disorder (Silver, 1964). We recently observed a child with otherwise typical features of the Russell-Silver syndrome who had enlargement of the right hand and of the left lower extremity. We know of no other recorded example of crossed asymmetry in this clinical entity. Images PMID:839508

Widespread porokeratotic adnexal ostial nevus: clinical features and proposal of a new name unifying porokeratotic eccrine ostial and dermal duct nevus and porokeratotic eccrine and hair follicle nevus.

PubMed

Goddard, Deborah S; Rogers, Maureen; Frieden, Ilona J; Krol, Alfons L; White, Clifton R; Jayaraman, Anu G; Robinson-Bostom, Leslie; Bruckner, Anna L; Ruben, Beth S

2009-12-01

Porokeratotic eccrine ostial and dermal duct nevus and a similar condition, porokeratotic eccrine and hair follicle nevus, are rare disorders of keratinization with eccrine and hair follicle involvement. We describe the clinical features in 5 patients, all of whom had widespread skin involvement following the lines of Blaschko. Two patients presented with erosions in the newborn period as the initial manifestation of their disease; one had an associated structural anomaly, unilateral breast hypoplasia; and one adult had malignant transformation in the nevus with development of multifocal squamous cell carcinomas. Three patients had histologic involvement of both acrosyringia and acrotrichia. Based on the observation of overlapping histologic features, we propose the name "porokeratotic adnexal ostial nevus" to incorporate the previously described entities porokeratotic eccrine ostial and dermal duct nevus and porokeratotic eccrine and hair follicle nevus.

The Alzheimer's Prevention Initiative Generation Program: Evaluating CNP520 Efficacy in the Prevention of Alzheimer's Disease.

PubMed

Lopez Lopez, C; Caputo, A; Liu, F; Riviere, M E; Rouzade-Dominguez, M-L; Thomas, R G; Langbaum, J B; Lenz, R; Reiman, E M; Graf, A; Tariot, P N

2017-01-01

Alzheimer's disease pathology begins decades before the onset of clinical symptoms. This provides an opportunity for interventional clinical trials to potentially delay or prevent the onset of cognitive impairment or dementia. CNP520 (a beta-site-amyloid precursor protein-cleaving enzyme inhibitor) is in clinical development for the treatment of preclinical Alzheimer's disease under the Alzheimer's Prevention Initiative Generation Program. The Alzheimer's Prevention Initiative is a public-private partnership intended to accelerate the evaluation of Alzheimer's disease prevention therapies. The Generation Program comprises two pivotal phase II/III studies with similar designs to assess the efficacy and safety of investigational treatments in a cognitively unimpaired population at increased risk for developing Alzheimer's disease based on age and apolipoprotein E (APOE) genotype (i.e., presence of the APOE ε4 allele). The program has been designed to maximize benefit to Alzheimer's disease research. Generation Study 1 (NCT02565511) and Generation Study 2 (NCT03131453) are currently enrolling; their key features are presented here.

Evaluation of the first seizure patient: Key points in the history and physical examination.

PubMed

Nowacki, Tomasz A; Jirsch, Jeffrey D

2017-07-01

This review will present the history and physical examination as the launching point of the first seizure evaluation, from the initial characterization of the event, to the exclusion of alternative diagnoses, and then to the determination of specific acute or remote causes. Clinical features that may distinguish seizures from alternative diagnoses are discussed in detail, followed by a discussion of acute and remote first seizure etiologies. This review article is based on a discretionary selection of English language articles retrieved by a literature search in the PubMed database, and the authors' clinical experience. The first seizure is a dramatic event with often profound implications for patients and family members. The initial clinical evaluation focuses on an accurate description of the spell to confirm the diagnosis, along with careful scrutiny for previously unrecognized seizures that would change the diagnosis more definitively to one of epilepsy. The first seizure evaluation rests primarily on the clinical history, and to a lesser extent, the physical examination. Even in the era of digital EEG recording and neuroimaging, the initial clinical evaluation remains essential for the diagnosis, treatment, and prognostication of the first seizure. Copyright © 2016. Published by Elsevier Ltd.

Open-angle glaucoma in the Petit Basset Griffon Vendeen.

PubMed

Bedford, Peter G C

2017-03-01

To report the prevalence and clinical characteristics of an open-angle glaucoma in Petit Basset Griffon Vendeen (PBGV) dogs in the United Kingdom (UK). At breed society clinics extending over a 6-year period, 366 dogs of varying ages and both sexes were clinically examined for signs of glaucoma using slit-lamp biomicroscopy, indirect and direct ophthalmoscopy, tonometry, and gonioscopy. The prevalence of glaucoma was 10.4% (38 dogs). Clinical signs of the disease presented from 3 years of age onwards, the commonest initial feature being the elevation of intraocular pressure (IOP) in 15 dogs (39.4%). In addition to elevated IOP, another 13 dogs (34.2%) presented with other features of glaucoma, some with lens subluxation and globe enlargement and all with possible or known vision defects. In the remaining 10 dogs (26.3%), phacodonesis or lens subluxation was observed before subsequent elevation of IOP. High prevalence and similarity to the primary open-angle glaucoma (POAG) seen in the Beagle and Elkhound breeds indicate that an open-angle glaucoma is present in the PBGV in the UK and that this disease may be genetically determined in this breed. Although increased IOP is the commonest early diagnostic feature, lens instability prior to an increase in IOP may be part of the clinical picture. © 2016 American College of Veterinary Ophthalmologists.

Prevalence, clinical features, and causes of epistaxis in dogs: 176 cases (1996-2001).

PubMed

Bissett, Sally A; Drobatz, Kenneth J; McKnight, Alexia; Degernes, Laurel A

2007-12-15

To determine prevalence, clinical features, and causes of epistaxis in dogs. Retrospective case series. 176 dogs with epistaxis. Medical records were reviewed for information related to signalment, clinical features, diagnosis, and outcome. 132 (75%) dogs were initially examined by the hospital's emergency service; prevalence of epistaxis was 0.3%. Dogs with epistaxis were more likely to be old (> or = 6 years), male, and large (> or = 26 kg [58.5 lb]) than were dogs in a reference population. In 109 (62%) dogs with epistaxis, an underlying cause was identified; 115 underlying disorders were identified, with 90 classified as local and 25 classified as systemic. Local causes of epistaxis included nasal neoplasia (n = 35), trauma (33), idiopathic rhinitis (20), and periapical abscess (2). Systemic causes included thrombocytopenia (12), thrombocytopathia (7), coagulopathy (3), hypertension (2), and vasculitis (1). Dogs with local causes were more likely to have unilateral than bilateral epistaxis, but 11 of 21 (52%) dogs with systemic disorders also had unilateral epistaxis. Dogs with systemic disorders were more likely to have clinical signs of systemic disease. Duration of epistaxis (acute vs chronic), severity, and duration of hospitalization were similar for dogs with local versus systemic disorders. Results suggested that epistaxis was a common disorder in dogs and frequently regarded as an emergency. Local causes of epistaxis were predominant, but clinical features traditionally thought to be helpful in distinguishing local versus systemic causes could not be reliably used for this purpose.

Demographic and clinical features of gout patients in Turkey: a multicenter study.

PubMed

Öztürk, Mehmet Akif; Kaya, Arif; Şenel, Soner; Dönmez, Salim; Balkarlı, Ayşe; Çobankara, Veli; Erhan, Çiğdem; Sayarlıoğlu, Mehmet; Ugan, Yunus; Tunç, Ş Ercan; Pehlivan, Yavuz; Kısacık, Bünyamin; Tufan, Abdurrahman; Onat, Ahmet Mesut; Tezcan, Engin; Yıldırım Çetin, Gözde; Pamuk, Omer Nuri

2013-04-01

Gout results from multifactor interactions between gender, age, genetic and environmental factors. Environmental factors underlying gout and precipitating factors triggering acute attacks might vary in different populations with different lifestyles. In this study, we aimed to collect data regarding the demographic and clinical features, comorbid factors, and precipitating factors associated with the initiation of acute attacks in gout patients in Turkey. A total of 312 patients were included in this study (mean age, 58.8 ± 13.8 years; female/male ratio, 55/257). The demographic features, alcohol intake, clinical and laboratory features, and comorbid conditions including obesity, diabetes mellitus, hyperlipidemia, hypertension, and coronary heart disease were noted in a standard questionnaire. Precipitating factors initiating acute attacks (if any) were also noted. The patients were divided into 4 groups according to the region of location as central Anatolian region, southeast Anatolian region, Aegean region, and Trakya region. Our results were compared according to the gender and the location of the patients. The mean age at the start of the symptoms was 10 years higher in women (60.4 ± 14.8 and 50.6 ± 13.5 years in women and men, respectively, p < 0.001).Obesity was present in 40.1 %, diabetes mellitus in 17.9 %, hyperlipidemia in 30.1 %, hypertension in 53.5 %, coronary artery disease in 17 %, and nephrolithiasis in 21.8 % of patients. Precipitating factors triggering gout flares were as follows: diet (high consumption of meat or fish) in 46.5 %, alcohol consumption in 15.7 %, diuretics in 8.3 %, diet or diuretics in 5.1 %, diet or alcohol in 4.5 %, diet or alcohol or diuretics in 1.6 %, others in 4.2 %, and none in 14.1 %. The presence of diabetes and diuretic use was more common among women. Use of diuretics is a more common trigger for gout flares among women. On the other hand, various comorbid conditions, such as obesity and hypertension, and triggers for gout flares may differ between patients living in different geographic regions. In summary, we reported the first data regarding clinical and demographic characteristics of gout in Turkey. The majority of our patients could describe at least one "trigger" that initiated gout flare. Both comorbid conditions and triggers of attack might differ between men and women, and in different geographic areas. Better knowledge of the modifiable risk factors can be useful for the management strategy to optimize long-term patient outcomes in local clinics.

Catatonia in Resource Limited Settings: A Case Series and Treatment Protocol

PubMed Central

Smith, Stephanie L.; Grelotti, David J.; Fils-Aime, Reginald; Uwimana, Eugenie; Ndikubwimana, Jean-Sauveur; Therosme, Tatiana; Severe, Jennifer; Dushimiyimana, Dominique; Uwamariya, Clemence; Bienvenu, Robert; Alcindor, Yoldie; Eustache, Eddy; Raviola, Giuseppe J.; Fricchione, Gregory L.

2014-01-01

Objective The Catatonic Syndrome (“catatonia”) is characterized by motor and motivation dysregulation and is associated with a number of neuropsychiatric and medical disorders. It is recognizable in a variety of clinical settings. We present observations from the treatment of four individuals with catatonia in Haiti and Rwanda, and introduce a treatment protocol for use in resource limited settings Methods Four patients from rural Haiti and Rwanda with clinical signs of catatonia and a positive screen using the Bush-Francis-Catatonia Rating Scale were treated collaboratively by general physicians and mental health clinicians with either lorazepam or diazepam. Success in treatment was clinically assessed by complete remittance of catatonia symptoms. Results The four patients in this report exhibited a range of characteristic and recognizable signs of catatonia, including immobility/stupor, stereotypic movements, echophenomena, posturing, odd mannerisms, mutism, and refusal to eat or drink. All four cases presented initially to rural outpatient general health services in low resource settings. In some cases, diagnostic uncertainty initially led to treatment with typical antipsychotics. In each case, proper identification and treatment of catatonia with benzodiazepines led to significant clinical improvement. Conclusion Catatonia can be effectively and inexpensively treated in resource limited settings. Identification and management of catatonia is critical for the health and safety of patients with this syndrome. Familiarity with the clinical features of catatonia is essential for health professionals working in low resource settings. To facilitate early recognition of this treatable disorder, catatonia should feature more prominently in global mental health discourse. PMID:25467078

THE MOLECULAR PATHOLOGY OF MELANOMA: AN INTEGRATED TAXONOMY OF MELANOCYTIC NEOPLASIA

PubMed Central

Bastian, Boris C.

2016-01-01

Melanomas are comprised of multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain of function mutations in one of several primary oncogenes, typically leading to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about pathogenesis, clinical, histological and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework. PMID:24460190

Occupational acroosteolysis in a guitar player.

PubMed

Baran, R; Tosti, A

1993-02-01

A case of occupational acroosteolysis in a 24-year-old classical guitar player is reported. Nail tenderness was the only manifestation of initial acroosteolysis, which was due to mechanical stress on the fingers. Radiographs showed initial resorption of the 2nd, 3rd and 4th finger of the left hand. The authors review the clinical and radiological features of acroosteolysis. The pathogenesis of acroosteolysis is discussed as well as the different diseases that may cause destructive changes of the distal phalangeal bones.

Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

PubMed

Chen, Zhi-Hai; Qin, Xin-Cheng; Song, Rui; Shen, Yi; Chen, Xiao-Ping; Wang, Wen; Zhao, Yong-Xiang; Zhang, Jing-Shan; He, Jin-Rong; Li, Ming-Hui; Zhao, Xue-Hua; Liu, De-Wei; Fu, Xiao-Kang; Tian, Di; Li, Xing-Wang; Xu, Jianguo; Plyusnin, Alexander; Holmes, Edward C; Zhang, Yong-Zhen

2014-01-01

Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

Clinical Features and Prognostic Factors of Hodgkin's Lymphoma: A Single Center Experience.

PubMed

Kılıçkap, Saadettin; Barışta, Ibrahim; Ulger, Sükran; Celik, Ismail; Selek, Uğur; Yıldız, Ferah; Kars, Ayşe; Ozışık, Yavuz; Tekuzman, Gülten

2013-06-01

Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Retrospective study. Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of "B" symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country.

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

PubMed

Tougeron, David; Savoye, Guillaume; Savoye-Collet, Céline; Koning, Edith; Michot, Francis; Lerebours, Eric

2009-08-01

Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

Reexpansion pulmonary edema in children

PubMed Central

Rodrigues, Antonio Lucas L.; Lopes, Carlos Eduardo; Romaneli, Mariana Tresoldi das N.; Fraga, Andrea de Melo A.; Pereira, Ricardo Mendes; Tresoldi, Antonia Teresinha

2013-01-01

OBJECTIVE To present a case of a patient with clinical and radiological features of reexpansion pulmonary edema, a rare and potentially fatal disease. CASE DESCRIPTION An 11-year-old boy presenting fever, clinical signs and radiological features of large pleural effusion initially treated as a parapneumonic process. Due to clinical deterioration he underwent tube thoracostomy, with evacuation of 3,000 mL of fluid; he shortly presented acute respiratory insufficiency and needed mechanical ventilation. He had an atypical evolution (extubated twice with no satisfactory response). Computerized tomography findings matched those of reexpansion edema. He recovered satisfactorily after intensive care, and pleural tuberculosis was diagnosed afterwards. COMMENTS Despite its rareness in the pediatric population (only five case reports gathered), the knowledge of this pathology and its prevention is very important, due to high mortality rates. It is recommended, among other measures, slow evacuation of the pleural effusion, not removing more than 1,500 mL of fluid at once. PMID:24142327

Ebola Virus Disease, Democratic Republic of the Congo, 2014.

PubMed

Nanclares, Carolina; Kapetshi, Jimmy; Lionetto, Fanshen; de la Rosa, Olimpia; Tamfun, Jean-Jacques Muyembe; Alia, Miriam; Kobinger, Gary; Bernasconi, Andrea

2016-09-01

During July-November 2014, the Democratic Republic of the Congo underwent its seventh Ebola virus disease (EVD) outbreak. The etiologic agent was Zaire Ebola virus; 66 cases were reported (overall case-fatality rate 74.2%). Through a retrospective observational study of confirmed EVD in 25 patients admitted to either of 2 Ebola treatment centers, we described clinical features and investigated correlates associated with death. Clinical features were mainly generic. At admission, 76% of patients had >1 gastrointestinal symptom and 28% >1 hemorrhagic symptom. The case-fatality rate in this group was 48% and was higher for female patients (67%). Cox regression analysis correlated death with initial low cycle threshold, indicating high viral load. Cycle threshold was a robust predictor of death, as were fever, hiccups, diarrhea, dyspnea, dehydration, disorientation, hematemesis, bloody feces during hospitalization, and anorexia in recent medical history. Differences from other outbreaks could suggest guidance for optimizing clinical management and disease control.

Classifying Clinical Trial Eligibility Criteria to Facilitate Phased Cohort Identification Using Clinical Data Repositories.

PubMed

Wang, Amy Y; Lancaster, William J; Wyatt, Matthew C; Rasmussen, Luke V; Fort, Daniel G; Cimino, James J

2017-01-01

A major challenge in using electronic health record repositories for research is the difficulty matching subject eligibility criteria to query capabilities of the repositories. We propose categories for study criteria corresponding to the effort needed for querying those criteria: "easy" (supporting automated queries), mixed (initial automated querying with manual review), "hard" (fully manual record review), and "impossible" or "point of enrollment" (not typically in health repositories). We obtained a sample of 292 criteria from 20 studies from ClinicalTrials.gov. Six independent reviewers, three each from two academic research institutions, rated criteria according to our four types. We observed high interrater reliability both within and between institutions. The analysis demonstrated typical features of criteria that map with varying levels of difficulty to repositories. We propose using these features to improve enrollment workflow through more standardized study criteria, self-service repository queries, and analyst-mediated retrievals.

Classifying Clinical Trial Eligibility Criteria to Facilitate Phased Cohort Identification Using Clinical Data Repositories

PubMed Central

Wang, Amy Y.; Lancaster, William J.; Wyatt, Matthew C.; Rasmussen, Luke V.; Fort, Daniel G.; Cimino, James J.

2017-01-01

A major challenge in using electronic health record repositories for research is the difficulty matching subject eligibility criteria to query capabilities of the repositories. We propose categories for study criteria corresponding to the effort needed for querying those criteria: “easy” (supporting automated queries), mixed (initial automated querying with manual review), “hard” (fully manual record review), and “impossible” or “point of enrollment” (not typically in health repositories). We obtained a sample of 292 criteria from 20 studies from ClinicalTrials.gov. Six independent reviewers, three each from two academic research institutions, rated criteria according to our four types. We observed high interrater reliability both within and between institutions. The analysis demonstrated typical features of criteria that map with varying levels of difficulty to repositories. We propose using these features to improve enrollment workflow through more standardized study criteria, self-service repository queries, and analyst-mediated retrievals. PMID:29854246

Easily obtainable clinical features increase the diagnostic accuracy for latent autoimmune diabetes in adults: an evidence-based report.

PubMed

Lutgens, Maurice W M D; Meijer, Melanie; Peeters, Babette; Poulsen, Marie-Louise N F; Rutten, Marjet J; Bots, Michiel L; van der Heijden, Geert J M G; Soedamah-Muthu, Sabita S

2008-12-01

Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose of oral glucose lowering drugs and their possible side effects. To assess which clinical features predict the presence or absence of LADA in patients older than 25 years presenting with hyperglycemia. A structured Medline and Embase search was conducted. Titles and abstracts were screened using predetermined selection criteria. Critical appraisal was based on standardized validity criteria for diagnostic research. One-hundred and eighty-four papers were retrieved of which after assessment of relevance and validity 2 studies remained for further analysis. One study reported a probability of LADA of 0.99 with one or two out of the following five clinical features: age at onset <50 years; acute symptoms; BMI<25 kg/m(2); a history of autoimmune disease; a family history positive for diabetes mellitus. The other study reported a probability of LADA of zero with none of the following clinical features and of 0.32 with one out of three: fasting blood glucose> or =15 mmol/l and/or HbA(1c)> or =10%; 10% reduction in body weight in the previous 3 months; BMI<25 kg/m(2). Further testing for LADA by measurement of autoimmune antibodies appears to be unnecessary in the absence of a specific set of clinical features. Before initiating therapy applying the above criteria may help to separate LADA from usual type 2 diabetes.

ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

PubMed Central

Hayreh, Sohan Singh

2011-01-01

The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual acuity improvement during the first 7 days differs significantly (p<0.001) among the 4 types of CRAO; among them, in eyes with initial visual acuity of counting finger or worse, visual acuity improved, remained stable or deteriorated in nonarteritic CRAO in 22%, 66% and 12% respectively; in nonarteritic CRAO with cilioretinal artery sparing in 67%, 33% and none respectively; and in transient nonarteritic CRAO in 82%, 18% and none respectively. Arteritic CRAO shows no change. Recent studies have shown that administration of local intra-arterial thrombolytic agent not only has no beneficial effect but also can be harmful. Prevalent multiple misconceptions on CRAO are discussed. Branch retinal artery occlusion Pathogeneses, clinical features and management of various types of BRAO are discussed at length. The natural history of visual acuity outcome shows a final visual acuity of 20/40 or better in 89% of permanent BRAO cases, 100% of transient BRAO and 100% of nonarteritic CLRAO alone. Cotton wools spots These are common, non-specific acute focal retinal ischemic lesions, seen in many retinopathies. Their pathogenesis and clinical features are discussed in detail. Amaurosis fugax Its pathogenesis, clinical features and management are described. PMID:21620994

Clinical significance of owl eye morphologic features by in vivo laser confocal microscopy in patients with cytomegalovirus corneal endotheliitis.

PubMed

Kobayashi, Akira; Yokogawa, Hideaki; Higashide, Tomomi; Nitta, Koji; Sugiyama, Kazuhisa

2012-03-01

To demonstrate the clinical significance of owl eye morphologic features observed by in vivo laser confocal microscopy in patients with cytomegalovirus (CMV) corneal endotheliitis. Observational case series. participants: Six eyes of 6 patients (6 men; mean age, 73.3 years) with cytomegalovirus corneal endotheliitis diagnosed by clinical manifestations together with polymerase chain reaction from aqueous humor samples. intervention: All patients were examined by slit-lamp biomicroscopy and in vivo laser confocal microscopy. main outcome measures: Clinical manifestations were summarized by reviewing medical records. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of abnormal cells and deposits. All patients had long histories of anterior uveitis with intraocular pressure elevation, corneal edema with keratic precipitates, and decrease of endothelial cell densities. Coin-shaped lesions were observed by slit lamp only in 1 patient at the first visit and in 2 additional patients at subsequent follow-up. In all patients, confocal microscopy demonstrated reduced subepithelial nerves, subepithelial opacity, increased reflectivity of keratocytes, highly reflective dots, and needle-shaped bodies. Owl eye morphologic features were observed consistently in all patients at the initial visit, and highly reflective round bodies were detected in 5 patients; most notably, these confocal features were reversible after resolution of endotheliitis. Owl eye morphologic features and highly reflective round bodies observed by confocal microscopy may be useful as an adjunct for the noninvasive diagnosis of cytomegalovirus corneal endotheliitis. Reversibility of these features after resolution of endotheliitis may be useful for monitoring the therapeutic effects without multiple anterior chamber tap. Copyright © 2012 Elsevier Inc. All rights reserved.

Antenatal Bartter syndrome presenting with vomiting and constipation mimicking subacute intestinal obstruction in a 20-day-old neonate.

PubMed

Abdelgadir, Ibtihal Siddiq; Elgharbawy, Fawzia; Salameh, Khalil Mohamad; Juma, Baha Eldin

2017-11-14

Antenatal Bartter syndrome is a rare condition that can present with different clinical features. These features include early onset maternal polyhydramnios, failure to thrive, prematurity and nephrocalcinosis.We are presenting this 20-day-old girl who had an antenatal history of polyhydramnios. She developed persistent non-bilious vomiting that was associated with constipation soon after birth. She presented with failure to thrive and features suggestive of intestinal obstruction. On the initial evaluation, she was noted to have hypokalaemic, hyponatraemic metabolic alkalosis. The initial work-up was done to exclude surgical and renal causes of her presentation, and the diagnosis was confirmed by gene analysis to be type III-classic Bartter syndrome. She was closely monitored for her growth and development with the appropriate salt replacement therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Precancerous Skin Lesions.

PubMed

Ferrándiz, C; Malvehy, J; Guillén, C; Ferrándiz-Pulido, C; Fernández-Figueras, M

Certain clinically and histologically recognizable skin lesions with a degree of risk of progression to squamous cell carcinoma have been traditionally grouped as precancerous skin conditions but now tend to be classified as in situ carcinomas. This consensus statement discusses various aspects of these lesions: their evaluation by means of clinical and histopathologic features, the initial evaluation of the patient, the identification of risk factors for progression, and the diagnostic and treatment strategies available today. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

NCI Releases Video: Proteogenomics Research - On the Frontier of Precision Medicine | Office of Cancer Clinical Proteomics Research

Cancer.gov

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announces the release of an educational video titled “Proteogenomics Research: On the Frontier of Precision Medicine."  Launched at the HUPO2017 Global Leadership Gala Dinner, catalyzed in part by the Cancer Moonshot initiative and featuring as keynote speaker the 47th Vice President of the United States of America Joseph R.

Sickle cell crisis leading to extensive necrosis in a low-grade glioma and masquerading high-grade lesion.

PubMed

Agrawal, Amit; Balpande, D N; Khan, A; Vagh, S J; Shukla, Samarth; Chopra, Sumit

2008-01-01

A 9-year-old female child presented with rapid neurological deterioration. Clinical features and imaging findings were suggestive of high-grade malignancy, and hematological investigations were suggestive of sickle cell trait. Histopathology showed features of low-grade malignancy and extensive intratumoral sickling. We hypothesize that the vicious cycle of hypoxia, sickling, thrombosis, ischemia and infarction resulted in the extensive tumor necrosis in the present case causing the initial symptoms and rapid deterioration in the condition of the patient. Copyright 2008 S. Karger AG, Basel.

Islet immunity and beta cell reserve of indigenous Black South Africans with ketoacidosis at initial diagnosis of diabetes.

PubMed

Ekpebegh, Chukwuma; Longo-Mbenza, Benjamin; Blanco-Blanco, Ernesto

2013-01-01

Islet immunity and beta cell reserve status were utilized to classify persons with ketoacidosis as the initial manifestation of diabetes. The clinical features of the various diabetes classes were also characterized. Prospective cross sectional study. Nelson Mandela Academic Hospital, Mthatha, Eastern Cape Province, South Africa. Indigenous Black South Africans with ketoacidosis as the initial manifestation of diabetes. Islet immunity and beta cell reserve were respectively assessed using serum anti-glutamic acid decarboxylase 65 (GAD) antibody and serum C-peptide after 1 mg of intravenous glucagon. Serum anti-GAD 65 antibody > or = 5 units/L and < 5 units/L, respectively defined anti-GAD 65 positive (A+) and negative (A-). Replete (beta+) and deplete (beta-) beta cell reserve were serum C-peptide after glucagon injection of > or = 0.5 ng/mL and < 0.5 ng/mL, respectively. The proportions of patients with A+beta-, A+beta+, A-beta- and A-beta+ and their clinical characteristics were determined. Of the 38 males and 33 females who participated in the study, patients were categorized in various classes: A-beta+, 46.5% (n=33/ 71); A-beta-, 26.8% (n=19/71); A+beta-, 22.5% (n=16/71); and A+beta+, 4.2% (n=3/71). The ages of the various classes were: 41.8 +/- 13.8 years for A-beta+ (n=33); 36.5 +/- 14.6 years for A-beta- (n=19); and 20.6 +/- 7.1 years for the combination of A+beta- with A+beta+ (n=19) (P<.0001, P<.0001 for the combination of A+beta- and A+beta+ vs A-beta+, P=.001 for the combination of A+beta- and A+beta+ vs A-beta-and P=.2 for A-beta- vs A-beta+. The clinical features of type 2 diabetes were most prevalent in A-beta+ class while the A+beta- and A+beta+ groups had the clinical profile of type 1A diabetes. Most of the indigenous Black South African patients with ketoacidosis as the initial manifestation of diabetes had islet immunity, beta cell reserve status and clinical profiles of type 2 diabetes.

[Clinico-pathologic Characteristics of Adult Patients with Atypical Infectious Mononucleosis].

PubMed

Yu, Ya-Ping; Song, Ping; An, Zhi-Ming; Zhou, Xiao-Gang; Li, Feng; Wang, Li-Ping; Mei, Jian-Gang; Zhai, Yong-Ping

2016-12-01

To investigate the clinicopathologic characteristics of adult patients with atypical infectious mononucleosis(IM). From January 2003 to December 2013, a total of 5 cases of atypical IM misdiagnosed as lymphoma were selected, and the clinico-pathological characteristics and efficacy of treatment were analyzed. Biopsy of lymph node or tonsil was performed to evaluate the possibility of lymphoma. Peripheral blood EBV antibody and EBV-DNA were examined by ELISA and real-time fluorescence quantitative PCR, respectively. All the cases were considered as lymphoma on the basis of morphological features in initial evaluation before relapse. These features included a florid immunoblastic proliferation, distortion of the underlying nodal or tonsillar architecture and the presence of necrosis. The immunophenotypic features, EBV encoded RNA (EBER) in situ hybridization and the gene rearrangement of immunoglobulin or T cell receptor may be helpful for the distinction of atypical IM from lymphoma. IM as EBV-related lymphoproliferative process shows marked clinical and histological diversity. Atypical case of IM may mimic many different type of lymphoma in clinical and pathologic features, and the misdiagnosis should be avoided by using molecular and pathological examination.

Clinical features of ocular toxoplasmosis in Korean patients.

PubMed

Park, Young-Hoon; Han, Jae-Hyung; Nam, Ho-Woo

2011-06-01

We report here the records of 10 consecutive Korean patients (10 eyes) with ocular toxoplasmosis which showed the typical clinical manifestations with seropositivity for Toxoplasma gondii specific IgG antibodies by micro-ELISA between 2006 and 2010. Nine patients were males and 1 was female; their age was 50.5 ± 13.8 years. The most common accompanying signs were vitritis (100%), anterior uveitis (70%), and scattered white deposit (80%). Pre-existing retinochoroidal scar was found in 1 (10%) patient. All patients received antiparasitic chemotherapy and systemic corticosteroid treatment, which resolved the presenting attack and recovered the visual acuity better than initial one in 9 patients and worse in 1. Optic atrophy, cataract, and retinal neovascularization were observed during the follow-up period and recurrence was detected in 3 eyes (30%) 6 to 20 months after the initial attack. In Korea, although rarely detected and reported, ocular toxoplasmosis needs more attention in clinical field of retinal diseases.

Managing and Communicating Operational Workflow: Designing and Implementing an Electronic Outpatient Whiteboard.

PubMed

Steitz, Bryan D; Weinberg, Stuart T; Danciu, Ioana; Unertl, Kim M

2016-01-01

Healthcare team members in emergency department contexts have used electronic whiteboard solutions to help manage operational workflow for many years. Ambulatory clinic settings have highly complex operational workflow, but are still limited in electronic assistance to communicate and coordinate work activities. To describe and discuss the design, implementation, use, and ongoing evolution of a coordination and collaboration tool supporting ambulatory clinic operational workflow at Vanderbilt University Medical Center (VUMC). The outpatient whiteboard tool was initially designed to support healthcare work related to an electronic chemotherapy order-entry application. After a highly successful initial implementation in an oncology context, a high demand emerged across the organization for the outpatient whiteboard implementation. Over the past 10 years, developers have followed an iterative user-centered design process to evolve the tool. The electronic outpatient whiteboard system supports 194 separate whiteboards and is accessed by over 2800 distinct users on a typical day. Clinics can configure their whiteboards to support unique workflow elements. Since initial release, features such as immunization clinical decision support have been integrated into the system, based on requests from end users. The success of the electronic outpatient whiteboard demonstrates the usefulness of an operational workflow tool within the ambulatory clinic setting. Operational workflow tools can play a significant role in supporting coordination, collaboration, and teamwork in ambulatory healthcare settings.

Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus.

PubMed

Joly, P; Richard, C; Gilbert, D; Courville, P; Chosidow, O; Roujeau, J C; Beylot-Barry, M; D'incan, M; Martel, P; Lauret, P; Tron, F

2000-10-01

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease characterized by the production of autoantibodies mainly directed against proteins of the plakin family. An overlapping distribution of autoantibody specificities has been recently reported between PNP, pemphigus vulgaris (PV), and pemphigus foliaceus (PF), which suggests a relationship between the different types of pemphigus. Our purpose was to evaluate the sensitivity and the specificity of clinical, histologic, and immunologic features in the diagnosis of PNP. The clinical, histologic, and immunologic features of 22 PNP patients were retrospectively reviewed and compared with those of 81 PV and PF patients without neoplasia and of 8 PV and 4 PF patients with various neoplasms. One clinical and 2 biologic features had both high sensitivity (82%-86%) and high specificity (83%-100%) whatever the control group considered: (1) association with a lymphoproliferative disorder, (2) indirect immunofluorescence (IIF) labeling of rat bladder, and (3) recognition of the envoplakin and/or periplakin bands in immunoblotting. Two clinicopathologic and two biologic features had high specificity (87%-100%) but poor sensitivity (27%-59%): (1) clinical presentation associating erosive oral lesions with erythema multiforme-like, bullous pemphigoid-like, or lichen planus-like cutaneous lesions; (2) histologic picture of suprabasal acantholysis with keratinocyte necrosis, interface changes, or lichenoid infiltrate; (3) presence of both anti-epithelial cell surface and anti-basement membrane zone antibodies by IIF; and (4) recognition of the desmoplakin I and/or BPAG1 bands in immunoblotting. Interestingly, 45% of patients with PNP presented initially with isolated oral erosions that were undistinguishable from those seen in PV patients, and 27% had histologic findings of only suprabasal acantholysis, which was in accordance with the frequent detection of anti-desmoglein 3 antibodies in PNP sera. The association with a lymphoproliferative disorder, the IIF labeling of rat bladder, and the immunoblotting recognition of envoplakin and/or periplakin are both sensitive and specific features in the diagnosis of PNP.

Differentiating cognitive impairment due to corticobasal degeneration and Alzheimer disease.

PubMed

Day, Gregory S; Lim, Tae Sung; Hassenstab, Jason; Goate, Alison M; Grant, Elizabeth A; Roe, Catherine M; Cairns, Nigel J; Morris, John C

2017-03-28

To identify clinical features that reliably differentiate individuals with cognitive impairment due to corticobasal degeneration (CBD) and Alzheimer disease (AD). Clinical features were compared between individuals with autopsy-proven CBD (n = 17) and AD (n = 16). All individuals presented with prominent cognitive complaints and were evaluated annually with semistructured interviews, detailed neurologic examinations, and neuropsychological testing. Substantial overlap was observed between individuals with dementia due to CBD and AD concerning presenting complaints, median (range) duration of symptoms before assessment (CBD = 3.0 [0-5.0] years, AD = 2.5 [0-8.0] years; p = 0.96), and median (range) baseline dementia severity (Clinical Dementia Rating Sum of Boxes: CBD = 3.5 [0-12.0], AD = 4.25 [0.5-9.0], p = 0.49). Subsequent emergence of asymmetric motor/sensory signs, hyperreflexia, gait abnormalities, parkinsonism, falls, urinary incontinence, and extraocular movement abnormalities identified individuals with CBD, with ≥3 discriminating features detected in 80% of individuals within 3.1 years (95% confidence interval 2.9-3.3) of the initial assessment. Individuals with CBD exhibited accelerated worsening of illness severity and declines in episodic memory, executive functioning, and letter fluency. Semiquantitative pathologic assessment revealed prominent tau pathology within the frontal and parietal lobes of CBD cases. Comorbid AD neuropathologic change was present in 59% (10 of 17) of CBD cases but did not associate with the clinical phenotype, rate of dementia progression, or dementia duration. CBD may mimic AD dementia early in its disease course. Interval screening for discriminating clinical features may improve antemortem diagnosis in individuals with CBD and prominent cognitive symptoms. © 2017 American Academy of Neurology.

Integrated Cox's model for predicting survival time of glioblastoma multiforme.

PubMed

Ai, Zhibing; Li, Longti; Fu, Rui; Lu, Jing-Min; He, Jing-Dong; Li, Sen

2017-04-01

Glioblastoma multiforme is the most common primary brain tumor and is highly lethal. This study aims to figure out signatures for predicting the survival time of patients with glioblastoma multiforme. Clinical information, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism array data of patients with glioblastoma multiforme were retrieved from The Cancer Genome Atlas. Patients were separated into two groups by using 1 year as a cutoff, and a logistic regression model was used to figure out any variables that can predict whether the patient was able to live longer than 1 year. Furthermore, Cox's model was used to find out features that were correlated with the survival time. Finally, a Cox model integrated the significant clinical variables, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism was built. Although the classification method failed, signatures of clinical features, messenger RNA expression levels, and microRNA expression levels were figured out by using Cox's model. However, no single-nucleotide polymorphisms related to prognosis were found. The selected clinical features were age at initial diagnosis, Karnofsky score, and race, all of which had been suggested to correlate with survival time. Both of the two significant microRNAs, microRNA-221 and microRNA-222, were targeted to p27 Kip1 protein, which implied the important role of p27 Kip1 on the prognosis of glioblastoma multiforme patients. Our results suggested that survival modeling was more suitable than classification to figure out prognostic biomarkers for patients with glioblastoma multiforme. An integrated model containing clinical features, messenger RNA levels, and microRNA expression levels was built, which has the potential to be used in clinics and thus to improve the survival status of glioblastoma multiforme patients.

Delays in initiation of acyclovir therapy in herpes simplex encephalitis.

PubMed

Hughes, Peter S; Jackson, Alan C

2012-09-01

Diagnosis of herpes simplex encephalitis (HSE) is based on clinical findings, MRI, and detection of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) using polymerase chain reaction amplification. Delays in starting treatment are associated with poorer clinical outcomes. We assessed the timing of initiation of acyclovir therapy in HSE. Inpatient databases from seven hospitals in Winnipeg, Manitoba were used to identify individuals diagnosed with encephalitis and HSE from 2004 to 2009. The time taken to initiate therapy with acyclovir and the reasons for delays were determined. Seventy-seven patients were identified; 69 (90%) received acyclovir; in the others a non-HSV infection was strongly suspected. Thirteen patients were subsequently confirmed to have HSE. Acyclovir was initiated a median of 21 hours (3-407) after presentation in encephalitis cases, and a median of 11 hours (3-118) in HSE. The most common reason for delay was a failure to consider HSE in the differential diagnosis, despite suggestive clinical features. Where therapy was delayed in HSE patients, the decision to begin acyclovir was prompted by transfer of the patient to a different service (55%), recommendations by consultants (18%), imaging results (18%), and CSF pleocytosis (9%). Delays in initiating acyclovir for HSE are common, and are most often due to a failure to consider HSE in a timely fashion on presentation. In order to improve patient outcomes, physicians should be more vigilant for HSE, and begin acyclovir therapy expeditiously on the basis of clinical suspicion rather than waiting for confirmatory tests.

Low-grade central osteosarcoma of distal femur, resembling fibrous dysplasia

PubMed Central

Vasiliadis, Haris S; Arnaoutoglou, Christina; Plakoutsis, Sotiris; Doukas, Michalis; Batistatou, Anna; Xenakis, Theodoros A

2013-01-01

We report a case of a 32 year-old male, admitted for a lytic lesion of the distal femur. One month after the first X-ray, clinical and imaging deterioration was evident. Open biopsy revealed fibrous dysplasia. Three months later, the lytic lesion had spread to the whole distal third of the femur reaching the articular cartilage. The malignant clinical and imaging features necessitated excision of the lesion and reconstruction with a custom-made total knee arthroplasty. Intra-operatively, no obvious soft tissue infiltration was evident. Nevertheless, an excision of the distal 15.5 cm of the femur including 3.0 cm of the surrounding muscles was finally performed. The histological examination of the excised specimen revealed central low-grade osteosarcoma. Based on the morphological features of the excised tumor, allied to the clinical findings, the diagnosis of low-grade central osteosarcoma was finally made although characters of a fibrous dysplasia were apparent. Central low-grade osteosarcoma is a rare, well-differentiated sub-type of osteosarcoma, with clinical, imaging, and histological features similar to benign tumours. Thus, initial misdiagnosis is usual with the condition commonly mistaken for fibrous dysplasia. Central low-grade osteosarcoma is usually treated with surgery alone, with rare cases of distal metastases. However, regional recurrence is quite frequent after close margin excision. PMID:24147271

Comorbid Normal Pressure Hydrocephalus with Parkinsonism: A Clinical Challenge and Call for Awareness.

PubMed

Cucca, A; Biagioni, M C; Sharma, K; Golomb, J; Gilbert, R M; Di Rocco, A; Fleisher, J E

2018-01-01

Idiopathic normal pressure hydrocephalus (iNPH) is the most common cause of hydrocephalus in adults. The diagnosis may be challenging, requiring collaborative efforts between different specialists. According to the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders, iNPH should be considered in the differential of any unexplained gait failure with insidious onset. Recognizing iNPH can be even more difficult in the presence of comorbid neurologic disorders. Among these, idiopathic Parkinson's disease (PD) is one of the major neurologic causes of gait dysfunction in the elderly. Both conditions have their peak prevalence between the 6th and the 7th decade. Importantly, postural instability and gait dysfunction are core clinical features in both iNPH and PD. Therefore, diagnosing iNPH where diagnostic criteria of PD have been met represents an additional clinical challenge. Here, we report a patient with parkinsonism initially consistent with PD who subsequently displayed rapidly progressive postural instability and gait dysfunction leading to the diagnosis of concomitant iNPH. In the following sections, we will review the clinical features of iNPH, as well as the overlapping and discriminating features when degenerative parkinsonism is in the differential diagnosis. Understanding and recognizing the potential for concomitant disease are critical when treating both conditions.

Spinal cord infarction: Clinical and imaging insights from the periprocedural setting.

PubMed

Zalewski, Nicholas L; Rabinstein, Alejandro A; Krecke, Karl N; Brown, Robert D; Wijdicks, Eelco F M; Weinshenker, Brian G; Doolittle, Derrick A; Flanagan, Eoin P

2018-05-15

Describe the range of procedures associated with spinal cord infarction (SCI) as a complication of a medical/surgical procedure and define clinical and imaging characteristics that could be applied to help diagnose spontaneous SCI, where the diagnosis is often less secure. We used an institution-based search tool to identify patients evaluated at Mayo Clinic, Rochester, MN from 1997 to 2016 with a periprocedural SCI. We performed a descriptive analysis of clinical features, MRI and other laboratory findings, and outcome. Seventy-five patients were identified with SCI related to an invasive or non-invasive surgery including: aortic aneurysm repair (49%); other aortic surgery (15%); and a variety of other procedures (e.g., cardiac surgery, spinal decompression, epidural injection, angiography, nerve block, embolization, other vascular surgery, thoracic surgery) (36%). Deficits were severe (66% para/quadriplegia) and maximal at first post-procedural evaluation in 61 patients (81%). Impaired dorsal column function was common on initial examination. Imaging features included classic findings of owl eyes or anterior pencil sign on MRI (70%), but several other T2-hyperintensity patterns were also seen. Gadolinium enhancement of the SCI and/or cauda equina was also common when assessed. Six patients (10%) had an initial normal MRI despite a severe deficit. Procedures associated with SCI are many, and this complication does not exclusively occur following aortic surgery. The clinical and radiologic findings that we describe with periprocedural SCI may be used in future studies to help distinguish spontaneous SCI from alternate causes of acute myelopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

PubMed

Hayashi, Naoki; Igarashi, Miyabi; Imai, Atsushi; Yoshizawa, Yuka; Asamura, Kaori; Ishikawa, Yoichi; Tokunaga, Taro; Ishimoto, Kayo; Tatebayashi, Yoshitaka; Harima, Hirohiko; Kumagai, Naoki; Ishii, Hidetoki; Okazaki, Yuji

2017-01-01

Suicidal behavior (SB) is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct. To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance. By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs) and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA. Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT), Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC) were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively. The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part of the process leading to SB. These results provide a base for further research into clinical strategies for patient management and therapy.

Clinical Features and Prognostic Factors of Hodgkin’s Lymphoma: A Single Center Experience

PubMed Central

Kılıçkap, Saadettin; Barışta, İbrahim; Ülger, Şükran; Çelik, İsmail; Selek, Uğur; Yıldız, Ferah; Kars, Ayşe; Özışık, Yavuz; Tekuzman, Gülten

2013-01-01

Background: Hodgkin’s lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. Aims: We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Study Design: Retrospective study. Methods: Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. Results: We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of “B” symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. Conclusion: This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country. PMID:25207097

A clinically viable capsule endoscopy video analysis platform for automatic bleeding detection

NASA Astrophysics Data System (ADS)

Yi, Steven; Jiao, Heng; Xie, Jean; Mui, Peter; Leighton, Jonathan A.; Pasha, Shabana; Rentz, Lauri; Abedi, Mahmood

2013-02-01

In this paper, we present a novel and clinically valuable software platform for automatic bleeding detection on gastrointestinal (GI) tract from Capsule Endoscopy (CE) videos. Typical CE videos for GI tract run about 8 hours and are manually reviewed by physicians to locate diseases such as bleedings and polyps. As a result, the process is time consuming and is prone to disease miss-finding. While researchers have made efforts to automate this process, however, no clinically acceptable software is available on the marketplace today. Working with our collaborators, we have developed a clinically viable software platform called GISentinel for fully automated GI tract bleeding detection and classification. Major functional modules of the SW include: the innovative graph based NCut segmentation algorithm, the unique feature selection and validation method (e.g. illumination invariant features, color independent features, and symmetrical texture features), and the cascade SVM classification for handling various GI tract scenes (e.g. normal tissue, food particles, bubbles, fluid, and specular reflection). Initial evaluation results on the SW have shown zero bleeding instance miss-finding rate and 4.03% false alarm rate. This work is part of our innovative 2D/3D based GI tract disease detection software platform. While the overall SW framework is designed for intelligent finding and classification of major GI tract diseases such as bleeding, ulcer, and polyp from the CE videos, this paper will focus on the automatic bleeding detection functional module.

Presentation and Diagnosis of Tuberous Sclerosis Complex in Infants.

PubMed

Davis, Peter E; Filip-Dhima, Rajna; Sideridis, Georgios; Peters, Jurriaan M; Au, Kit Sing; Northrup, Hope; Bebin, E Martina; Wu, Joyce Y; Krueger, Darcy; Sahin, Mustafa

2017-12-01

Tuberous sclerosis complex (TSC) is a neurocutaneous genetic disorder with a high prevalence of epilepsy and neurodevelopmental disorders. TSC can be challenging to diagnose in infants because they often do not show many clinical signs early in life. In this study, we describe the timing and pattern of presenting and diagnostic features in a prospective longitudinal study of infants with TSC. Two multicenter, prospective studies enrolled 130 infants with definite TSC by clinical or genetic criteria and followed them longitudinally up to 36 months of age. Periodic study visits included medical and seizure histories, physical and neurologic examinations, and developmental assessments. Ages at which major and minor features of TSC and seizures were first identified were analyzed. The most common initial presenting features of TSC were cardiac rhabdomyomas (59%) and hypomelanotic macules or other skin findings (39%), and 85% of infants presented with either or both. Ultimately, the most prevalent diagnostic TSC features were hypomelanotic macules (94%), tubers or other cortical dysplasias (94%), subependymal nodules (90%), and cardiac rhabdomyomas (82%). Thirty-five percent of infants presented prenatally, 41% presented at birth or within the first month of life, and 74% met criteria for TSC diagnosis at or within 30 days of presentation. Seizure onset occurred before or at initial presentation in only 15% of infants, but 73% developed epilepsy within the first year of life. Infants with TSC can often be identified early, before the onset of neurologic sequelae, enabling earlier diagnosis, surveillance, and possibly disease-modifying treatment. Copyright © 2017 by the American Academy of Pediatrics.

Comparison of the epidemiologic features and patterns of initial care for prostate cancer between public and private institutions: a survey by the Brazilian Society of Urology.

PubMed

Nardi, Aguinaldo Cesar; Reis, Rodolfo Borges dos; Zequi, Stenio de Cassio; Nardozza, Archimedes

2012-01-01

To describe the epidemiological features and patterns of initial care for prostate cancer at public and private institutions in the State of Sao Paulo, Brazil. A total of 1,082 physicians affiliated to the Sao Paulo Section of the Brazilian Society of Urology were invited to participate in this cross-sectional, web-based survey. Between September 2004 and September 2005, participating urologists entered data on demographic, clinical and pathological characteristics of patients diagnosed with prostate cancer in their practice. Data on patients attended at public institutions were analyzed and compared with those patients attended at private practice. One hundred and ten society members contributed with data from 1915 patients, 1026 (53.6%) of whom from public institutions. When compared with patients attended at private institutions, those attended at public institutions were older and more likely to be black, had higher serum prostate specific antigen (PSA) levels, had a higher probability of being diagnosed with metastatic disease, but were less likely to undergo prostatectomy (all P < 0.001). In multivariate analysis, age, biopsy Gleason score, and being attended at a public institution were independently associated with metastatic disease upon diagnosis. The significant predictors of nonsurgical treatment were age, black race, and higher serum levels of PSA. A statewide registry provides valuable information regarding patient demographics, clinical features, and patterns of care. The results of this study suggest that significant disparities exist for patients with prostate cancer attended at different health-care systems. The relative contribution of biological versus socioeconomic features remains uncertain.

Odontogenic keratocyst: The role of the orthodontist in the diagnosis of initial lesions.

PubMed

Leandro Santos, Raphaela Silva; Ramos-Perez, Flávia Maria de Moraes; Silva, Gleyson Kleber do Amaral; Rocha, André Caroli; Prado, José Divaldo; Perez, Danyel Elias da Cruz

2017-10-01

Odontogenic keratocysts (OKCs) are locally infiltrative odontogenic cysts that are usually diagnosed during routine radiographic examinations. Therefore, it is critical that dental practitioners, in particular orthodontists, recognize and diagnose OKCs to recommend appropriate treatment. This report describes a patient whose OKC was not initially identified during orthodontic pretreatment. In addition, this report discusses the clinical and radiographic features of OKCs, as well as the differential diagnoses of these lesions. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE.

PubMed

Casciola-Rosen, L; Rosen, A

1997-01-01

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease which is characterized clinically by pleiotropy and periodicity. The immune features which accompany the characteristic flares of the disease have strongly suggested that the autoimmune response is driven by self antigen, and is T cell-dependent. These features have prompted the search for potential initiating process(es) which induce the release of self-antigens in a form which causes T cell tolerance to those self molecules to be broken. We review here several recent observations which implicate apoptotic cells as an important potential source of clustered and concentrated autoantigens in SLE, and present our current model whereby the novel autoantigen fragments generated in apoptotic surface blebs initiate and drive the autoimmune response in this disease.

Program development and defining characteristics of returning military in a VA Polytrauma Network Site.

PubMed

Lew, Henry L; Poole, John H; Vanderploeg, Rodney D; Goodrich, Gregory L; Dekelboum, Sharon; Guillory, Sylvia B; Sigford, Barbara; Cifu, David X

2007-01-01

The conflicts in Iraq and Afghanistan have resulted in a new generation of combat survivors with complex physical injuries and emotional trauma. This article reports the initial implementation of the Polytrauma Network Site (PNS) clinic, which is a key component of the Department of Veterans Affairs (VA) Polytrauma System of Care and serves military personnel returning from combat. The PNS clinic in Palo Alto, California, is described to demonstrate the VA healthcare system's evolving effort to meet the clinical needs of this population. We summarize the following features of this interdisciplinary program: (1) sequential assessment, from initial traumatic brain injury screening throughout our catchment area to evaluation by the PNS clinic team, and (2) clinical evaluation results for the first 62 clinic patients. In summary, this population shows a high prevalence of postconcussion symptoms, posttraumatic stress, poor cognitive performance, head and back pain, auditory and visual symptoms, and problems with dizziness or balance. An anonymous patient feedback survey, which we used to fine-tune the clinic process, reflected high satisfaction with this new program. We hope that the lessons learned at one site will enhance the identification and treatment of veterans with polytrauma across the country.

Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

PubMed

Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

2017-06-15

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo.

PubMed

von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T; Wagner, Denisa D; Mackman, Nigel; Engelmann, Bernd; Massberg, Steffen

2012-04-09

Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features.

Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo

PubMed Central

von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A.; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T.; Wagner, Denisa D.; Mackman, Nigel; Engelmann, Bernd

2012-01-01

Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features. PMID:22451716

Clinical features of adult-onset chronic active Epstein-Barr virus infection: a retrospective analysis.

PubMed

Arai, Ayako; Imadome, Ken-Ichi; Watanabe, Yuko; Yoshimori, Mayumi; Koyama, Takatoshi; Kawaguchi, Takeharu; Nakaseko, Chiaki; Fujiwara, Shigeyoshi; Miura, Osamu

2011-05-01

We performed a retrospective analysis of patients with adult-onset chronic active Epstein-Barr virus infection (CAEBV). First, we analyzed five patients (aged 28-72) diagnosed at our hospitals with EBV-infected clonally proliferating T cells. Four patients were administered cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) chemotherapy, but no remarkable decrease of viral load was observed in three of the patients. The other patient died 19 days after initiation of CHOP treatment due to disease progression. Addition of high-dose cytarabine to the regimens of two of the patients was discontinued shortly after administration, due to the development of grade 4 pericardial effusion. Together, these regimens may be insufficient for treating adult-onset CAEBV. We next reviewed 23 adult-onset CAEBV patients, adding 18 previously reported patients to the five patients described in the present study. T cells were frequently infected (87%), whereas NK- and T-cell types are known to be almost equally prevalent in childhood-onset cases. The time duration from the onset of disease to initiation of treatment averaged 20 months. Reports showed that 12 patients died; seven patients died at an average of 8 months after initiation of treatment. Patients' disease courses seemed to be rapidly progressive and more aggressive than those of childhood-onset cases. More cases must be studied to clarify clinical features and establish an optimal treatment strategy.

The prognostic impact of clinical and CT parameters in patients with pontine hemorrhage.

PubMed

Dziewas, Rainer; Kremer, Marion; Lüdemann, Peter; Nabavi, Darius G; Dräger, Bianca; Ringelstein, Bernd

2003-01-01

In patients with pontine hemorrhage (PH), an accurate prognostic assessment is critical for establishing a reasonable therapeutic approach. The initial clinical symptoms and computed tomography (CT) features were analyzed with multivariate regression analysis in 39 consecutive patients with PH. PHs were classified into three types: (1) large paramedian, (2) basal or basotegmental and (3) lateral tegmental, and the hematomas' diameters were measured. The patients' outcome was evaluated. Twenty-seven patients (69%) died and 12 (31%) survived for more than 1 year after PH. The symptom most predictive of death was coma on admission. The large paramedian type of PH predicted a poor prognosis, whereas the lateral tegmental type was associated with a favorable outcome. The transverse hematoma diameter was also related to outcome, with the threshold value found to be 20 mm. We conclude that PH outcome can be estimated best by combining the CT parameters 'large paramedian PH' and 'transverse diameter >/=20 mm' with the clinical variable 'coma on admission'. Survival is unlikely if all 3 features are present, whereas survival may be expected if only 1 or none of these features is found. Copyright 2003 S. Karger AG, Basel

Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein-Taybi and Filippi syndromes.

PubMed

de Vries, Tamar I; Monroe, Glen R; van Belzen, Martine J; van der Lans, Christian A; Savelberg, Sanne Mc; Newman, William G; van Haaften, Gijs; Nievelstein, Rutger A; van Haelst, Mieke M

2016-08-01

Rubinstein-Taybi syndrome (RTS, OMIM 180849) and Filippi syndrome (FLPIS, OMIM 272440) are both rare syndromes, with multiple congenital anomalies and intellectual deficit (MCA/ID). We present a patient with intellectual deficit, short stature, bilateral syndactyly of hands and feet, broad thumbs, ocular abnormalities, and dysmorphic facial features. These clinical features suggest both RTS and FLPIS. Initial DNA analysis of DNA isolated from blood did not identify variants to confirm either of these syndrome diagnoses. Whole-exome sequencing identified a homozygous variant in C9orf173, which was novel at the time of analysis. Further Sanger sequencing analysis of FLPIS cases tested negative for CKAP2L variants did not, however, reveal any further variants. Subsequent analysis using DNA isolated from buccal mucosa revealed a mosaic variant in CREBBP. This report highlights the importance of excluding mosaic variants in patients with a strong but atypical clinical presentation of a MCA/ID syndrome if no disease-causing variants can be detected in DNA isolated from blood samples. As the striking syndactyly observed in the present case is typical for FLPIS, we suggest CREBBP analysis in saliva samples for FLPIS syndrome cases in which no causal CKAP2L variant is detected.

Thirty-Year (1975–2005) Trends in the Incidence Rates, Clinical Features, Treatment Practices, and Short-term Outcomes of Patients < 55 Years of Age Hospitalized with an Initial Acute Myocardial Infarction

PubMed Central

McManus, David D.; Piacentine, Stephen M; Lessard, Darleen; Gore, Joel M.; Yarzebski, Jorge; Spencer, Frederick A.; Goldberg, Robert J.

2011-01-01

Sparse data are available describing recent trends in the magnitude, clinical features, treatment practices, and outcomes of comparatively young adults hospitalized with acute myocardial infarction (AMI). The objectives of this population-based study were to describe 3 decade-long trends (1975–2005) in these endpoints among adults less than 55 years old who were hospitalized with an initial AMI. The study population consisted of 1,703 residents of the Worcester (MA) metropolitan area between the ages of 25–54 years who were hospitalized with an initial AMI at all central Massachusetts medical centers during 15 annual periods between 1975 and 2005. The overall hospital incidence rate (per 100,000 persons) of initial AMI in our study population was 66 (95% confidence interval 63–69) and the incidence rates of AMI declined inconsistently over time. Patients hospitalized during the most recent study years were more likely to have important cardiovascular risk factors and comorbidities present but were less likely to have developed heart failure during their index hospitalization. In-hospital and 30-day death rates declined by approximately 50% (p = 0.04) during the years under study concomitant with increasing use of effective cardiac therapies. In conclusion, the results of this community-wide investigation provide insights into the magnitude, changing characteristics, and short-term outcomes of comparatively young patients hospitalized with a first AMI. Declining odds of developing, or dying from, an initial AMI during the 30 years under study likely reflect enhanced primary and secondary prevention and treatment efforts. PMID:21624538

Social work in dentistry: the CARES model for improving patient retention and access to care.

PubMed

Doris, Joan M; Davis, Elaine; Du Pont, Cynthia; Holdaway, Britt

2009-07-01

Social work programs in dental schools and dental clinics have been operated successfully since the 1940s, and have been documented as contributing to patients' access to care and to dental education. However, unlike medical social work, with which it has much in common, social work in dentistry has failed to become a standard feature of dental schools and clinics. Few of the social work initiatives that have been implemented in dental schools have survived after initial grant funding ran out, or the institutional supporters of the program moved on. The authors hope that the CARES program serves as a model for the successful development of other programs at the intersection of social work and dentistry to the benefit of both dental patients and providers.

Diagnosis of Metastasis to the Thyroid Gland: Comparison of Core-Needle Biopsy and Fine-Needle Aspiration.

PubMed

Choi, Sang Hyun; Baek, Jung Hwan; Ha, Eun Ju; Choi, Young Jun; Song, Dong Eun; Kim, Jae Kyun; Chung, Ki-Wook; Kim, Tae Yong; Lee, Jeong Hyun

2016-04-01

Early detection and diagnosis of metastasis to the thyroid gland is important. This study aims to evaluate the clinical value of core-needle biopsy (CNB) by comparing the results of CNB and fine-needle aspiration (FNA) in patients with clinically suspected metastasis to the thyroid gland. Case series with chart review. Tertiary referral practice. Fifty-two thyroid nodules from 52 patients with clinically suspected metastasis to the thyroid gland (mean age, 62.8 years). Of these 52 patients, FNA was initially used in 41 patients and CNB in 20 patients (11 patients as the initial approach and 9 patients after inconclusive FNA results). Ultrasound features of metastasis to the thyroid gland were evaluated. The diagnostic performance, repeated diagnostic examination rate, and diagnostic surgery rate were evaluated for FNA and CNB. Among these 52 patients, 46 were diagnosed with thyroid metastases and 6 were diagnosed with primary thyroid cancer. Common ultrasound features were an ovoid to round shape (58.7%), ill-defined margin (56.5%), hypoechogenicity (65.2%), and no calcifications (87.0%). Core-needle biopsy achieved a significantly higher sensitivity than FNA (100.0% vs 58.6%, P = .008) without any false-negative results. Both the repeated diagnostic examination rate and the diagnostic surgery rate were significantly lower in CNB than in FNA (5.0% vs 46.3%, P = .001, and 5.0% vs 34.1%, P = .013, respectively). In cases of known rare primary malignancy, nontypical ultrasound features of primary thyroid malignancy, and need for an additional immunohistochemical analysis, CNB may be primarily considered. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Idiopathic Hypersomnia: Clinical Features and Response to Treatment

PubMed Central

Ali, Mohsin; Auger, R. Robert; Slocumb, Nancy L.; Morgenthaler, Timothy I.

2009-01-01

Objective: A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. Methods: A retrospective review of our database initially identified 997 patients, utilizing “idiopathic hypersomnia,” “hypersomnia NOS,” and “primary hypersomnia” as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. Results: Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a “complete response” to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of “complete” or “partial” responses than modafinil, although statistical significance was not reached (38/40 [ 95%] vs 22/25 [88%], respectively, p = 0.291). Conclusions: The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored. Citation: Ali M; Auger RR; Slocumb NL; Morgenthaler TI. Idiopathic hypersomnia: clinical features and response to treatment. J Clin Sleep Med 2009;5(6):562-568. PMID:20465024

[A case of hereditary sensory and autonomic neuropathy type 1E with frontal lobe dysfunction as an initial symptom].

PubMed

Watanabe, Masashi; Matsumoto, Yushi; Okamoto, Kensho; Okuda, Bungo; Mizuta, Ikuko; Mizuno, Toshiki

2017-12-27

A 49-year-old man had developed gradually personality change, gait disturbance, and hearing loss for five years. On admission, he presented with frontal release signs, stuttering, vertical gaze palsy, sensorineural deafness, muscle rigidity, ataxia, and sensory disturbance with areflexia in the lower extremities. Brain MRI demonstrated atrophy in the cerebellum and midbrain tegmentum as well as cerebral atrophy, predominantly in the frontal lobe. He was tentatively diagnosed as progressive supranuclear palsy on the basis of clinical features and imagings. On nerve conduction study, no sensory nerve action potentials were elicited in the upper and lower extremities. Details of family history revealed a hereditary sensory neuropathy with autosomal dominant inheritance in his relatives. Because genetic analysis showed a rare missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene, we diagnosed him as having hereditary sensory and autonomic neuropathy type 1E (HSAN1E). In addition, p.M232R mutation in prion protein gene was detected. It should be kept in mind that there are some patients with HSAN1E presenting with frontal lobe dysfunction as an initial symptom and with clinical features mimicking progressive supranuclear palsy.

Churg-Strauss syndrome: a new endotype of severe asthma? Results of 14 Turkish patients.

PubMed

Yılmaz, İnsu; Çelik, Gülfem; Aydın, Ömür; Özdemir, Seçil Kepil; Soyyiğit, Şadan; Sözener, Zeynep; Özgüçlü, Selcan; Atasoy, Çetin; Düzgün, Nurşen; Mungan, Dilşad; Sin, Betül; Demirel, Yavuz Selim; Mısırlıgil, Zeynep

2015-07-01

Churg-Strauss syndrome (CSS) is a rare multisystem vasculitis. Considering the variation of autoimmune diseases in different races, it is of interest to determine whether any outstanding features exist for Turkish patients with CSS. The aim of this study was to evaluate the clinical and serological features of the disease, the treatment, and long-term follow-up details, and to investigate possible etiological factors of Turkish CSS patients. The study included 14 patients who were diagnosed with CSS, and followed by our department between 2004 and 2012. Possible etiological factors, initial symptoms, clinical presentations, treatment, as well as outcomes were documented. The study was approved by the local ethics. All patients fulfilled the American College of Rheumatology criteria. Initial symptoms were worsening asthma (n = 14; 100%) and skin lesions (n = 6; 43%). All patients had a diagnosis of asthma and nasal polyps, whereas 57.1% had aspirin hypersensitivity at the time of diagnosis. The lungs (100%) and skin (43%) were most commonly involved. Peripheral eosinophilia dominated on initial presentations of all patients. Initial treatments included oral methyl prednisolone in all cases, whereas cyclophosphamide and azathioprine were used in three cases. Relapses were detected in five cases. None of the cases were able to stop the oral corticosteroid treatment. No fatalities were observed. We herein describe a new severe asthma endotype in connection with CSS. We suggest that physicians who deal with uncontrolled severe asthma cases should consider CSS in the presence of nasal polyps, aspirin hypersensitivity, and especially peripheral blood eosinophilia over 10%. © 2014 John Wiley & Sons Ltd.

Revisiting the concept of late catatonia.

PubMed

Kocha, Hiroki; Moriguchi, Sho; Mimura, Masaru

2014-10-01

The objective of this paper is to introduce the concept of late catatonia to foreign readers for the first time in English. The original study was conducted about 20 years ago. The subjects were 16 persons who first visited our institutions between 1990 and 1996. They fulfilled the following criteria: 1) late-onset psychosis, with the initial mental changes occurring after 40 years of age; 2) more than one catatonic symptom observed during the clinical course; 3) a total clinical course lasting more than 2 years; and 4) no evidence of apparent organic brain disease. The medical records of individual patients were retrospectively reviewed to summarize the clinical features of this diagnosis. The crucial feature was the evolution or longitudinal change in the clinical picture over time, with the clinical course being divided into five stages: stage I (prodromal depression), stage II (anxiety and agitation), stage III (hallucination and delusion), stage IV (catatonia syndrome), and residual state. As for treatment, the effect of psychotropic agents was very limited. The electroconvulsive treatment was the most effective treatment option. Apart from the current diagnostic dichotomy of schizophrenia and mood disorder, the concept of late catatonia is useful in clinical settings and may provide clinically important knowledge. Copyright © 2014 Elsevier Inc. All rights reserved.

Early-Onset LMNA-Associated Muscular Dystrophy with Later Involvement of Contracture.

PubMed

Lee, Younggun; Lee, Jung Hwan; Park, Hyung Jun; Choi, Young Chul

2017-10-01

The early diagnosis of LMNA-associated muscular dystrophy is important for preventing sudden arrest related to cardiac conduction block. However, diagnosing early-onset Emery-Dreifuss muscular dystrophy (EDMD) with later involvement of contracture and limb-girdle muscular dystrophy type 1B is often delayed due to heterogeneous clinical presentations. We aimed to determine the clinical features that contribute to a delayed diagnosis. We reviewed four patients who were recently diagnosed with LMNA-associated muscular dystrophy by targeted exome sequencing and who were initially diagnosed with nonspecific or other types of muscular dystrophy. Certain clinical features such as delayed contracture involvement and calf hypertrophy were found to contribute to a delayed diagnosis. Muscle biopsies were not informative for the diagnosis in these patients. Genetic testing of single or multiple genes is useful for confirming a diagnosis of LMNA-associated muscular dystrophy. Even EDMD patients could experience the later involvement of contracture, so clinicians should consider early genetic testing for patients with undiagnosed muscular dystrophy or laminopathy. Copyright © 2017 Korean Neurological Association

Infrastructure Requirements for an Urgent-Start Peritoneal Dialysis Program

PubMed Central

Ghaffari, Arshia; Kumar, Vijay; Guest, Steven

2013-01-01

Patients with advanced chronic kidney disease nearing dialysis but without pre-established access almost uniformly initiate dialysis with a temporary central venous catheter. These catheters are associated with high rates of infection and flow disturbances, requiring removal and subsequent replacement. Many of these patients might be candidates for peritoneal dialysis (PD), but because of the absence of prior catheter placement, the default initial modality is hemodialysis. Recent reports, however, have demonstrated the feasibility of initiating PD urgently despite the late referral for access placement. Urgent-start PD clinical pathways require a unique infrastructure and treatment approach. This article reviews the salient features required to establish an urgent-start PD program. PMID:24335123

Differentiating cognitive impairment due to corticobasal degeneration and Alzheimer disease

PubMed Central

Day, Gregory S.; Lim, Tae Sung; Hassenstab, Jason; Goate, Alison M.; Grant, Elizabeth A.; Roe, Catherine M.; Cairns, Nigel J.

2017-01-01

Objective: To identify clinical features that reliably differentiate individuals with cognitive impairment due to corticobasal degeneration (CBD) and Alzheimer disease (AD). Methods: Clinical features were compared between individuals with autopsy-proven CBD (n = 17) and AD (n = 16). All individuals presented with prominent cognitive complaints and were evaluated annually with semistructured interviews, detailed neurologic examinations, and neuropsychological testing. Results: Substantial overlap was observed between individuals with dementia due to CBD and AD concerning presenting complaints, median (range) duration of symptoms before assessment (CBD = 3.0 [0–5.0] years, AD = 2.5 [0–8.0] years; p = 0.96), and median (range) baseline dementia severity (Clinical Dementia Rating Sum of Boxes: CBD = 3.5 [0–12.0], AD = 4.25 [0.5–9.0], p = 0.49). Subsequent emergence of asymmetric motor/sensory signs, hyperreflexia, gait abnormalities, parkinsonism, falls, urinary incontinence, and extraocular movement abnormalities identified individuals with CBD, with ≥3 discriminating features detected in 80% of individuals within 3.1 years (95% confidence interval 2.9–3.3) of the initial assessment. Individuals with CBD exhibited accelerated worsening of illness severity and declines in episodic memory, executive functioning, and letter fluency. Semiquantitative pathologic assessment revealed prominent tau pathology within the frontal and parietal lobes of CBD cases. Comorbid AD neuropathologic change was present in 59% (10 of 17) of CBD cases but did not associate with the clinical phenotype, rate of dementia progression, or dementia duration. Conclusions: CBD may mimic AD dementia early in its disease course. Interval screening for discriminating clinical features may improve antemortem diagnosis in individuals with CBD and prominent cognitive symptoms. PMID:28235814

Pragmatic characteristics of patient-reported outcome measures are important for use in clinical practice.

PubMed

Kroenke, Kurt; Monahan, Patrick O; Kean, Jacob

2015-09-01

Measures for assessing patient-reported outcomes (PROs) that may have initially been developed for research are increasingly being recommended for use in clinical practice as well. Although psychometric rigor is essential, this article focuses on pragmatic characteristics of PROs that may enhance uptake into clinical practice. Three sources were drawn on in identifying pragmatic criteria for PROs: (1) selected literature review including recommendations by other expert groups; (2) key features of several model public domain PROs; and (3) the authors' experience in developing practical PROs. Eight characteristics of a practical PRO include: (1) actionability (i.e., scores guide diagnostic or therapeutic actions/decision making); (2) appropriateness for the relevant clinical setting; (3) universality (i.e., for screening, severity assessment, and monitoring across multiple conditions); (4) self-administration; (5) item features (number of items and bundling issues); (6) response options (option number and dimensions, uniform vs. varying options, time frame, intervals between options); (7) scoring (simplicity and interpretability); and (8) accessibility (nonproprietary, downloadable, available in different languages and for vulnerable groups, and incorporated into electronic health records). Balancing psychometric and pragmatic factors in the development of PROs is important for accelerating the incorporation of PROs into clinical practice. Published by Elsevier Inc.

Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

PubMed Central

2013-01-01

Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

Clinical and subclinical leaks after low colorectal anastomosis: a clinical and radiologic study.

PubMed

Lim, Michael; Akhtar, Saleem; Sasapu, Kishore; Harris, Keith; Burke, Dermot; Sagar, Peter; Finan, Paul

2006-10-01

This study was designed to examine the natural history of subclinical leaks and their effect on bowel function and quality of life and to evaluate water-soluble contrast enema features that predict anastomotic healing after leaks. Consecutive patients who underwent low rectal anastomosis were followed up postoperatively for leaks. All leaks were confirmed radiologically with CT scanning and water-soluble contrast enema imaging. Water-soluble contrast enemas were serially repeated to identify healing. Characteristics on initial water-soluble contrast enema were correlated with observed healing. Postoperatively, patients were required to fill in a quality of life and a bowel function questionnaire. A total of 138 patients underwent low rectal anastomosis procedures with a median follow-up period of 26 (interquartile range, 19-37) months. There were 23 documented leaks of which 13 (9 percent) presented clinically and 10 (8 percent) presented subclinically. Ileostomy closure was possible in 4 of 13 (30 percent) patients with a clinical leak and all 10 (100 percent) patients with a subclinical leak. Median quality of life scores were lower for patients with clinical leaks and no ileostomy closure (P = 0.03). Bowel function for subclinical leak patients and clinical leak patients with ileostomy closure were similarly impaired. The presence of a cavity (P = 0.01) and a stricture (P = 0.01) at the anastomotic site were unfavorable radiologic features associated with nonhealing. Subclinical leaks are more benign in their natural history compared with clinical leaks. Quality of life and bowel function is no better in patients with a subclinical leak compared with patients with a clinical leak who have ileostomy closure. Anastomotic leaks may resolve if favorable radiologic features are present.

Managing and Communicating Operational Workflow

PubMed Central

Weinberg, Stuart T.; Danciu, Ioana; Unertl, Kim M.

2016-01-01

Summary Background Healthcare team members in emergency department contexts have used electronic whiteboard solutions to help manage operational workflow for many years. Ambulatory clinic settings have highly complex operational workflow, but are still limited in electronic assistance to communicate and coordinate work activities. Objective To describe and discuss the design, implementation, use, and ongoing evolution of a coordination and collaboration tool supporting ambulatory clinic operational workflow at Vanderbilt University Medical Center (VUMC). Methods The outpatient whiteboard tool was initially designed to support healthcare work related to an electronic chemotherapy order-entry application. After a highly successful initial implementation in an oncology context, a high demand emerged across the organization for the outpatient whiteboard implementation. Over the past 10 years, developers have followed an iterative user-centered design process to evolve the tool. Results The electronic outpatient whiteboard system supports 194 separate whiteboards and is accessed by over 2800 distinct users on a typical day. Clinics can configure their whiteboards to support unique workflow elements. Since initial release, features such as immunization clinical decision support have been integrated into the system, based on requests from end users. Conclusions The success of the electronic outpatient whiteboard demonstrates the usefulness of an operational workflow tool within the ambulatory clinic setting. Operational workflow tools can play a significant role in supporting coordination, collaboration, and teamwork in ambulatory healthcare settings. PMID:27081407

Detection of relationships among multi-modal brain imaging meta-features via information flow.

PubMed

Miller, Robyn L; Vergara, Victor M; Calhoun, Vince D

2018-01-15

Neuroscientists and clinical researchers are awash in data from an ever-growing number of imaging and other bio-behavioral modalities. This flow of brain imaging data, taken under resting and various task conditions, combines with available cognitive measures, behavioral information, genetic data plus other potentially salient biomedical and environmental information to create a rich but diffuse data landscape. The conditions being studied with brain imaging data are often extremely complex and it is common for researchers to employ more than one imaging, behavioral or biological data modality (e.g., genetics) in their investigations. While the field has advanced significantly in its approach to multimodal data, the vast majority of studies still ignore joint information among two or more features or modalities. We propose an intuitive framework based on conditional probabilities for understanding information exchange between features in what we are calling a feature meta-space; that is, a space consisting of many individual featurae spaces. Features can have any dimension and can be drawn from any data source or modality. No a priori assumptions are made about the functional form (e.g., linear, polynomial, exponential) of captured inter-feature relationships. We demonstrate the framework's ability to identify relationships between disparate features of varying dimensionality by applying it to a large multi-site, multi-modal clinical dataset, balance between schizophrenia patients and controls. In our application it exposes both expected (previously observed) relationships, and novel relationships rarely considered investigated by clinical researchers. To the best of our knowledge there is not presently a comparably efficient way to capture relationships of indeterminate functional form between features of arbitrary dimension and type. We are introducing this method as an initial foray into a space that remains relatively underpopulated. The framework we propose is powerful, intuitive and very efficiently provides a high-level overview of a massive data space. In our application it exposes both expected relationships and relationships very rarely considered worth investigating by clinical researchers. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical features and radiological evaluation of otic capsule sparing temporal bone fractures.

PubMed

Song, S W; Jun, B C; Kim, H

2017-03-01

To evaluate the clinical and radiological aspects of otic capsule sparing temporal bone fractures. Using medical records, 188 temporal bones of 173 patients with otic capsule sparing temporal bone fractures were evaluated. Otoscopic findings and symptoms, facial paralysis, and hearing loss were assessed. Using regional analysis, 7 fractures were classified as type I, 85 as type II, 169 as type III and 114 as type IV. Fourteen of the 17 facial paralysis cases improved to House-Brackmann grade II or lower at an average of 57.6 days after the initial evaluation. Thirty-one patients underwent initial and follow-up pure tone audiometry examinations. The air-bone gap closed significantly from 27.2 dB at an average of 21.8 days post-trauma to 19.6 dB at an average of 79.9 days post-trauma, without the need for surgical intervention. Initial conservative treatment for facial paralysis or conductive hearing loss is possible in otic capsule sparing fracture cases after careful evaluation of the patient.

Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia

PubMed Central

Hodges, John R.; Knopman, David; Mendez, Mario F.; Kramer, Joel H.; Neuhaus, John; van Swieten, John C.; Seelaar, Harro; Dopper, Elise G. P.; Onyike, Chiadi U.; Hillis, Argye E.; Josephs, Keith A.; Boeve, Bradley F.; Kertesz, Andrew; Seeley, William W.; Rankin, Katherine P.; Johnson, Julene K.; Gorno-Tempini, Maria-Luisa; Rosen, Howard; Prioleau-Latham, Caroline E.; Lee, Albert; Kipps, Christopher M.; Lillo, Patricia; Piguet, Olivier; Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D.; Fox, Nick C.; Galasko, Douglas; Salmon, David P.; Black, Sandra E.; Mesulam, Marsel; Weintraub, Sandra; Dickerson, Brad C.; Diehl-Schmid, Janine; Pasquier, Florence; Deramecourt, Vincent; Lebert, Florence; Pijnenburg, Yolande; Chow, Tiffany W.; Manes, Facundo; Grafman, Jordan; Cappa, Stefano F.; Freedman, Morris; Grossman, Murray; Miller, Bruce L.

2011-01-01

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines. PMID:21810890

Pattern analysis of nerve enlargement using ultrasonography in chronic inflammatory demyelinating polyneuropathy.

PubMed

Jang, Jae Hong; Cho, Charles S; Yang, Kyung-Sook; Seok, Hung Youl; Kim, Byung-Jo

2014-09-01

Focal nerve enlargement is a characteristic finding in chronic inflammatory demyelinating polyneuropathy (CIDP). We performed this study to assess the distribution of nerve enlargement through ultrasonographic examination of peripheral nerves and to correlate the ultrasonographic findings with clinical features. To compare the ultrasonographic features of 10 subjects with CIDP with those of 18 healthy controls, we bilaterally measured the cross-sectional areas (CSA) of the vagus, brachial plexus, musculocutaneous, median, ulnar, radial, sciatic, tibial, common peroneal, and sural nerves. We also analyzed correlations between CSAs and various clinical and electrophysiological features. Mean CSAs were significantly larger in CIDP patients than controls, especially at proximal and non-entrapment sites. CSAs were significantly correlated with muscle strength at initial presentation, but not at the time of ultrasonography. The CSAs of the median and ulnar nerves at the mid-forearm, tibial nerve at 7 cm proximal to the medial malleolus, and sural nerve correlated with the nerve conduction velocity of the corresponding region. Ultrasonography revealed widely distributed nerve enlargement, especially in proximal regions and non-entrapment sites, in patients with CIDP compared with healthy controls. Nerve enlargement correlated well with the electrophysiologic function of the nerve, but not current clinical status. Pattern analysis of nerve enlargement using ultrasonography is a supportive tool in the diagnosis of CIDP. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Trends in Diagnosis and Clinical Features of Melanoma in situ in U.S. Men and Women: a prospective, observational study

PubMed Central

Wei, Erin X.; Qureshi, Abrar A.; Han, Jiali; Li, Tricia Y.; Cho, Eunyoung; Lin, Jennifer Y.; Li, Wen-Qing

2016-01-01

Background The incidence of melanoma in situ is rising, but little is known about its characteristics. Objective To determine trends in diagnosis and clinical features of melanoma in situ. Methods Incident cases of melanoma were collected prospectively from the Nurses’ Health Study from 1976–2010 and Health Professionals Follow-up Study from 1986–2010. Results MIS incidence increased from 2 to 42 per 100,000-person-year (100KPY) among women, and from 11 to 73 per 100KPY among men, exceeding the rate of increase of invasive melanomas. Melanoma mortality initially increased during the follow-up period then plateaued. Men were more likely than women to develop in situ melanomas on upper half of the body (p<0.001). Invasive melanomas were diagnosed at a younger age than melanoma in situ (p<0.001), and were more likely to be found on the lower extremities than in situ melanomas (p<0.001). Limitations This is a strictly descriptive study without examination into mechanisms. Conclusion We found epidemiologic and clinical differences in in situ and invasive melanomas, which support further examination into the variations in etiologic pathways. The lack of improvement in mortality despite increase in detection of in situ relative to invasive lesions further highlight the need to improve invasive melanoma-specific clinical screening features. PMID:27436155

The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics.

PubMed

McGovern, Eavan M; Roze, Emmanuel; Counihan, Timothy J

2018-05-15

This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions. Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection. In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.

Watchful waiting and factors predictive of secondary treatment of localized prostate cancer.

PubMed

Wu, Hongyan; Sun, Leon; Moul, Judd W; Wu, Hong Yu; McLeod, David G; Amling, Christopher; Lance, Raymond; Kusuda, Leo; Donahue, Timothy; Foley, John; Chung, Andrew; Sexton, Wade; Soderdahl, Douglas

2004-03-01

Watchful waiting remains an important treatment option for some patients with localized prostate cancer. We defined the demographic, clinical and outcome features of men selecting watchful waiting as an initial treatment strategy, and determined factors predictive of eventual progression to secondary treatment. Of 8390 patients diagnosed with prostate cancer from 1990 to 2001 in the Department of Defense Center for Prostate Disease Research Database, 1158 patients chose watchful waiting as initial treatment. The demographic and clinical differences between patients on watchful waiting and those choosing other initial treatments were compared using the chi-square test. Secondary treatment-free survival according to various prognostic factors was plotted using the Kaplan-Meier method and differences were tested using the log rank test. A multivariate Cox proportional hazards regression analysis was performed to determine which factors were independent predictors of secondary treatment. Compared to other patients, those selecting watchful waiting were older, had lower prostate specific antigen (PSA) at diagnosis, and were more likely to have lower stage (cT1) and lower grade (Gleason sum 7 or less) cancers. Age, PSA and clinical stage were all significant and independent predictors of secondary treatment. The relative risk of secondary treatment can be expressed as EXP (-0.034 x age at diagnosis + 0.284 x LOG (diagnostic PSA) + 0.271 x clinical stage T2 + 0.264 x clinical stage T3). Men who elect watchful waiting as initial management for prostate cancer are older with lower Gleason sums and serum PSA. In these men, age at diagnosis, serum PSA and clinical stage are the most significant predictors of requiring or selecting secondary treatment.

Clinical and genetic features of Australian families with long QT syndrome: A registry-based study.

PubMed

Burns, Charlotte; Ingles, Jodie; Davis, Andrew M; Connell, Vanessa; Gray, Belinda; Hunt, Lauren; McGaughran, Julie; Semsarian, Christopher

2016-12-01

Familial long QT syndrome (LQTS) is a primary arrhythmogenic disorder caused by mutations in ion channel genes. The phenotype ranges from asymptomatic individuals to sudden cardiac arrest and death. LQTS is a rare but significant health problem for which global data should exist. This study sought to provide the first clinical and genetic description of Australian families with LQTS. We performed a cross-sectional study to evaluate clinical and genetic features of families with LQTS. We recruited individuals from the Australian Genetic Heart Disease Registry and Genetic Heart Disease Clinic, in Sydney, Australia, and included those with a diagnosis of LQTS according to the most recent consensus statement. Among 108 families with LQTS, 173 individuals were affected. Twenty-five (32%) probands had a sudden cardiac death (SCD) event (including appropriate implantable cardioverter defibrillator [ICD] therapy, or resuscitated cardiac arrest). There were 64 (82%) probands who underwent genetic testing, and 34 (53%) had a pathogenic or likely pathogenic mutation in. Having a family history of LQTS was significantly associated with identification of a pathogenic result (79% versus 14%, p <0.0001). There were 16 (9%) participants who experienced delay to diagnosis of at least 12 months. This is the first clinical and genetic study in a large cohort of Australian families with LQTS. Findings from this study suggest that the clinical and genetic features in this population are not dissimilar to those described in North American, European, and Asian cohorts. Global-scale information about families with LQTS is an important initiative to ensure diagnostic and management approaches are applicable to different populations and ethnicities.

Hypothyroidism simulating as polymyositis.

PubMed

Aslam, Hina; Sayeed, Mohammad Ahsan; Qadeer, Rashid; Afsar, Salahuddin

2015-05-01

Polymyositis-like syndrome in hypothyroidism is a rare condition characterised by proximal muscle weakness and elevated muscle enzymes. Patients with this condition can initially be misdiagnosed as having polymyositis due to similar characteristics of both diseases; however a response to thyroxine is the main differentiating feature. This report highlights the case of a 30-year-old male who had severe myalgia and proximal muscle weakness. In addition to raised creatinine phosphokinase (CPK) levels, his biochemical profile showed hypothyroidism. Initially thought to be suffering from polymyositis, improvement in both clinical and biochemical profile with thyroxine led to the diagnosis of polymyositis-like syndrome associated with hypothyroidism.

Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet.

PubMed

Taub, Katherine S; Kessler, Sudha Kilaru; Bergqvist, A G Christina

2014-04-01

Few studies have examined the long-term sustainability of complete seizure freedom on the ketogenic diet (KD). The purpose of this study was to describe the risk of seizure recurrence in children who achieved at least 1 month of seizure freedom on the KD, and to assess clinical features associated with sustained seizure freedom. Records of patients initiated on the KD at The Children's Hospital of Philadelphia (CHOP) from 1991 to 2009 were reviewed. Subjects who attained seizure freedom for at least 1 month within 2 years were included in the study. Seizure frequency was recorded based on caregiver-reported seizure diaries as unchanged, improved, or worse compared to baseline. Those patients with seizure freedom ≥1 year were compared to those with seizure freedom <1 year in terms of demographics, age of seizure onset, number of antiepileptic drugs (AEDs) prior to KD, and epilepsy classification. Of 276 patients initiated on the KD, 65 patients (24%) attained seizure freedom for a minimum of 1 month. The majority of these patients had daily seizures. The median time to seizure freedom after KD initiation was 1.5 months. Seizures recurred in 53 patients (82%), with a median time to seizure recurrence of 3 months. However, seizure frequency after initial recurrence remained far less than baseline. No clinical features were identified as risk factors for seizure recurrence. Seizure recurrence on the KD after 1 month of seizure freedom most often occurred as occasional breakthrough seizures and not a return to baseline seizure frequency. This study provides evidence to support the continued use of the KD in patients with initial seizure freedom even after breakthrough seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients.

PubMed

Julia, F; Petrella, T; Beylot-Barry, M; Bagot, M; Lipsker, D; Machet, L; Joly, P; Dereure, O; Wetterwald, M; d'Incan, M; Grange, F; Cornillon, J; Tertian, G; Maubec, E; Saiag, P; Barete, S; Templier, I; Aubin, F; Dalle, S

2013-09-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease characterized by malignant proliferation of a contingent blastic plasmacytoid dendritic cell. This rare entity is recognized mostly by cutaneous spreading, or not having a leukaemic component. The prognosis is very poor. To study a large cohort of 90 patients with BPDCN, to define additional symptoms to form a correct diagnosis earlier, and to manage such patients accordingly. We retrospectively reviewed BPDCN cases registered in the French Study Group on Cutaneous Lymphoma database between November 1995 and January 2012. Ninety patients were studied. Demographic data, clinical presentation, initial staging and outcome were recorded. The group contained 62 male and 28 female patients (sex ratio 2·2). Their ages ranged from 8 to 103 years at the time of diagnosis (mean 67·2 years). Three major different clinical presentations were identified. Sixty-six patients (73%) presented with nodular lesions only, 11 patients (12%) with 'bruise-like' patches and 13 (14%) with disseminated lesions (patches and nodules). Mucosal lesions were seen in five patients (6%). The median survival in patients with BPDCN was 12 months. We here distinguish three different clinical presentations of BPDCN. A nodular pattern is a more common feature than the originally reported 'bruise-like' pattern. Despite the fact that BPDCN may initially appear as a localized skin tumour, aggressive management including allogeneic bone marrow transplantation should be considered immediately, as it is currently the only option associated with long-term survival. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

An initial investigation of abnormal bodily phenomena in subjects at ultra high risk for psychosis: Their prevalence and clinical implications.

PubMed

Madeira, Luis; Bonoldi, Ilaria; Rocchetti, Matteo; Samson, Carly; Azis, Matilda; Queen, Beverly; Bossong, Matthijs; Perez, Jesus; Stone, James; Allen, Paul; Howes, Oliver D; McGuire, Philip; Raballo, Andrea; Fusar-Poli, Paolo; Ballerini, Massimo; Stanghellini, Giovanni

2016-04-01

Contemporary phenomenological research has considered abnormal bodily phenomena (ABP) to be a phenotypic trait of subjects with schizophrenia in their first psychotic episode. Yet the prevalence of ABP and their clinical significance in subjects at Ultra High Risk (UHR) of psychosis remain unidentified. This study is an exploratory investigation of ABP in UHR subjects and matched healthy controls (HCs) examining their relation to clinical features and basic self-disturbances. A sample of 26 UHR and 14 HC subjects from three prodromal and early intervention clinics in South London, West London and Cambridge was assessed with the Abnormal Bodily Phenomena questionnaire (ABPq), Comprehensive Assessment of At-Risk Mental States (CAARMS), the Positive and Negative Syndrome Scale (PANSS), the Social and Occupational Functioning Assessment Scale (SOFAS) and the Examination of Anomalous Self Experiences (EASE) checklist. In our sample ABP occurred in 73.1% of UHR subjects and prominent ABP (proABP) were referred in 53.8% of them. No HC subject reported ABP. The UHR group with proABP had lower CAARMS total score (t=-9.265, p=0.006). There were no differences in PANSS total score (t=-1.235, p=0.277), SOFAS score (H(2) 22.27, p=0.666) and EASE total scores (z=8.565, adjusted p=0.185) in the UHR subjects with prominent ABP versus those that did not. This initial investigation suggests that ABP could be a prevalent phenotypic feature of UHR subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

Epidemiological findings and clinical and magnetic resonance presentations in subacute sclerosing panencephalitis.

PubMed

Cece, H; Tokay, L; Yildiz, S; Karakas, O; Karakas, E; Iscan, A

2011-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, inflammatory neurodegenerative disease. This study investigated the relationships of clinical stage with epidemiological and magnetic resonance imaging (MRI) findings in SSPE by retrospective review of 76 cases (57 male) diagnosed by typical periodic electroencephalographic features, clinical symptoms and elevated measles antibody titre in cerebrospinal fluid. Clinical stage at diagnosis was I or II in 48 patients, III in 25 and IV in three. Prominent findings at presentation were atonic/myoclonic seizures (57.9%) and mental deterioration with behaviour alteration (30.3%). Frequent MRI findings (13 - 32 patients) were subcortical, periventricular and cortical involvement and brain atrophy; the corpus callosum, basal ganglia, cerebellum and brainstem were less frequently involved. Five patients had pseudotumour cerebri. Cranial MRI at initial diagnosis was normal in 21 patients (19 stage I/II, two stage III/IV). Abnormal MRI findings were significantly more frequent in the later stages, thus a normal initial cranial MRI does not exclude SSPE, which should, therefore, be kept in mind in childhood demyelinating diseases even when the presentation is unusual.

NewYork-Presbyterian Hospital: translating innovation into practice.

PubMed

Johnson, Trudy; Currie, Gail; Keill, Patricia; Corwin, Steven J; Pardes, Herbert; Cooper, Mary Reich

2005-10-01

NewYork-Presbyterian (NYP) Hospital, a 2,242-bed not-for-profit academic medical center, was formed by a merger of The New York Hospital and The Presbyterian Hospital in the City of New York. It is also the flagship for the NewYork-Presbyterian Healthcare System, with 37 acute care facilities and 18 others. The hospital embeds safety in the culture through strategic initiatives and enhances service and efficiency using Six Sigma and other techniques to drive adoption of improvements. Goals are selected in alignment with the annual strategic initiatives, which are chosen on the basis of satisfaction surveys, patient and family complaints, community advisory groups, and performance measures, among other sources. A new business intelligence system enables online, dynamic analysis of performance results, replacing static paper reports. Advanced features in the clinical information systems include computerized physician order entry; interactive clinical alerts for decision support; a real-time infection control tracking system; and a clinical data warehouse supporting data mining and analysis for quality improvement, decision making, and education. To achieve clinical, service, and operational excellence, NYP focuses on all Institute of Medicine quality aims.

Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

PubMed

Fujishiro, Hiroshige; Iritani, Shuji; Hattori, Miho; Sekiguchi, Hirotaka; Matsunaga, Shinji; Habuchi, Chikako; Torii, Youta; Umeda, Kentaro; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

2015-09-01

Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

Customizing our approach in deep vein thrombosis and pulmonary embolism treatment: overview of our clinical experience.

PubMed

Turpie, A G

1999-08-01

Until recently, the management of established deep vein thrombosis (DVT) and pulmonary embolism remained largely unchanged and unchallenged. Treatment comprised an initial intravenous bolus of unfractionated heparin (UFH), followed by dose-adjusted intravenous UFH for 5-7 days, and oral warfarin for three months. UFH is traditionally administered in hospital, and monitoring and dose adjustment remain essential features of both UFH and warfarin treatment, making therapy both costly and inconvenient. Recent clinical trials have shown that subcutaneous UFH, or low-molecular-weight heparins (LMWHs), administered subcutaneously at a weight-adjusted fixed dose, are at least as effective as standard UFH given intravenously in the treatment of DVT. The feasibility of initial treatment of DVT at home in selected patients, with associated cost-savings and improved convenience have also been demonstrated with LMWHs. Clinical trials are currently investigating the potential value of LMWHs in the treatment of pulmonary embolism and as an alternative to warfarin in secondary prevention of DVT. The role of newer anticoagulants, such as recombinant hirudin, in initial treatment of DVT, and of thrombolysis in the management of pulmonary embolism remain to be defined.

Goodpasture’s Disease: An Uncommon Disease With an Atypical Clinical Course

PubMed Central

Shiferaw, Bethel; Miro, Viktor; Smith, Carroll; Akella, Jagadish; Chua, Walter; Kim, Zae

2016-01-01

Goodpasture’s disease is an uncommon composite of features including renal failure with pulmonary hemorrhage secondary to an autoimmune response that specifically targets these organ systems. We present a case of particular interest in regards to atypical presentation, and the uncommon treatment that the patient underwent. A 65-year-old Afghani female arrived with complaints of nausea, vomiting, loss of appetite, malaise, decreased urine output, exertional dyspnea, and cough. The patient presented initially with renal failure and unexpectedly developed respiratory failure after hemodialysis. Initial CT of thorax revealed diffuse bilateral pulmonary edema. Subsequently, the patient received a bronchoscopy demonstrating alveolar hemorrhage, which highlights a clinician’s need to maintain a differential and reassess patients. Anti-GBM antibody in the serum was detected and the renal biopsy revealed evidence of the antibody on immunofluorescence. In regards to management, the patient could only be treated with plasmapheresis as she had contraindication to initiation of immunosuppression, after which she showed significant clinical improvement. We would like to highlight the benefit of plasmapheresis without concomitant immunosuppression and recommend such an approach to be considered in similar clinical scenarios, where contraindication for immunosuppressant therapy exists. PMID:26668684

Jaffe-Campanacci syndrome.

PubMed

Al-Rikabi, Ammar C; Ramaswamy, Jyothi C; Bhat, Venkatraman V

2005-01-01

This case report describes the clinical, radiological and histopathological features of the Jaffe-Campanacci syndrome as seen in a 6-year-old Qatari male patient who was initially misdiagnosed as a case of systemic neurofibromatosis. Our case has all the diagnostic stigmata of Jaffe-Campanacci syndrome as described in the literature and these include cafe au lait macules, skeletal deformities and multiple histologically confirmed non-ossifying fibromas of the long bones.

Clinics in diagnostic imaging (153). Severe hypoxic ischaemic brain injury.

PubMed Central

Chua, Wynne; Lim, Boon Keat; Lim, Tchoyoson Choie Cheio

2014-01-01

A 58-year-old Indian woman presented with asystole after an episode of haemetemesis, with a patient downtime of 20 mins. After initial resuscitation efforts, computed tomography of the brain, obtained to evaluate neurological injury, demonstrated evidence of severe hypoxic ischaemic brain injury. The imaging features of hypoxic ischaemic brain injury and the potential pitfalls with regard to image interpretation are herein discussed. PMID:25091891

Evaluating online diagnostic decision support tools for the clinical setting.

PubMed

Pryor, Marie; White, David; Potter, Bronwyn; Traill, Roger

2012-01-01

Clinical decision support tools available at the point of care are an effective adjunct to support clinicians to make clinical decisions and improve patient outcomes. We developed a methodology and applied it to evaluate commercially available online clinical diagnostic decision support (DDS) tools for use at the point of care. We identified 11 commercially available DDS tools and assessed these against an evaluation instrument that included 6 categories; general information, content, quality control, search, clinical results and other features. We developed diagnostically challenging clinical case scenarios based on real patient experience that were commonly missed by junior medical staff. The evaluation was divided into 2 phases; an initial evaluation of all identified and accessible DDS tools conducted by the Clinical Information Access Portal (CIAP) team and a second phase that further assessed the top 3 tools identified in the initial evaluation phase. An evaluation panel consisting of senior and junior medical clinicians from NSW Health conducted the second phase. Of the eleven tools that were assessed against the evaluation instrument only 4 tools completely met the DDS definition that was adopted for this evaluation and were able to produce a differential diagnosis. From the initial phase of the evaluation 4 DDS tools scored 70% or more (maximum score 96%) for the content category, 8 tools scored 65% or more (maximum 100%) for the quality control category, 5 tools scored 65% or more (maximum 94%) for the search category, and 4 tools score 70% or more (maximum 81%) for the clinical results category. The second phase of the evaluation was focused on assessing diagnostic accuracy for the top 3 tools identified in the initial phase. Best Practice ranked highest overall against the 6 clinical case scenarios used. Overall the differentiating factor between the top 3 DDS tools was determined by diagnostic accuracy ranking, ease of use and the confidence and credibility of the clinical information. The evaluation methodology used here to assess the quality and comprehensiveness of clinical DDS tools was effective in identifying the most appropriate tool for the clinical setting. The use of clinical case scenarios is fundamental in determining the diagnostic accuracy and usability of the tools.

Primary Undifferentiated Pleomorphic Sarcoma of the Penis

PubMed Central

Yoo, Hyung Sun; Satti, Suma

2017-01-01

Background: Primary penile sarcoma is a rare disease that affects men of all ages. Different subtypes of primary penile sarcoma exist, with the rarest being pleomorphic sarcoma. Delays in presentation and diagnosis of primary penile sarcoma have been reported because of its benign-appearing presenting features and rarity. If penile sarcoma is left untreated, the clinical consequence is metastasis that is fatal in most cases. Case Report: We report an extremely rare case of undifferentiated pleomorphic sarcoma of the penis in a 59-year-old patient who initially presented with a slow-growing penile nodule. The tumor was surgically excised, but the patient experienced local recurrence and, despite receiving chemotherapy and surgery, died of metastatic disease 15 months after initial presentation. Conclusion: Vigilance regarding biopsy and intervention for penile nodules may lead to early diagnosis and improved clinical outcomes. PMID:29230132

Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2.

PubMed

Jack, Clifford R; Barnes, Josephine; Bernstein, Matt A; Borowski, Bret J; Brewer, James; Clegg, Shona; Dale, Anders M; Carmichael, Owen; Ching, Christopher; DeCarli, Charles; Desikan, Rahul S; Fennema-Notestine, Christine; Fjell, Anders M; Fletcher, Evan; Fox, Nick C; Gunter, Jeff; Gutman, Boris A; Holland, Dominic; Hua, Xue; Insel, Philip; Kantarci, Kejal; Killiany, Ron J; Krueger, Gunnar; Leung, Kelvin K; Mackin, Scott; Maillard, Pauline; Malone, Ian B; Mattsson, Niklas; McEvoy, Linda; Modat, Marc; Mueller, Susanne; Nosheny, Rachel; Ourselin, Sebastien; Schuff, Norbert; Senjem, Matthew L; Simonson, Alix; Thompson, Paul M; Rettmann, Dan; Vemuri, Prashanthi; Walhovd, Kristine; Zhao, Yansong; Zuk, Samantha; Weiner, Michael

2015-07-01

Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Development and initial evaluation of an instrument to assess physiotherapists' clinical reasoning focused on clients' behavior change.

PubMed

Elvén, Maria; Hochwälder, Jacek; Dean, Elizabeth; Söderlund, Anne

2018-05-01

A systematically developed and evaluated instrument is needed to support investigations of physiotherapists' clinical reasoning integrated with the process of clients' behavior change. This study's aim was to develop an instrument to assess physiotherapy students' and physiotherapists' clinical reasoning focused on clients' activity-related behavior and behavior change, and initiate its evaluation, including feasibility and content validity. The study was conducted in three phases: 1) determination of instrument structure and item generation, based on a model, guidelines for assessing clinical reasoning, and existing measures; 2) cognitive interviews with five physiotherapy students to evaluate item understanding and feasibility; and 3) a Delphi process with 18 experts to evaluate content relevance. Phase 1 resulted in an instrument with four domains: Physiotherapist; Input from client; Functional behavioral analysis; and Strategies for behavior change. The instrument consists of case scenarios followed by items in which key features are identified, prioritized, or interpreted. Phase 2 resulted in revisions of problems and approval of feasibility. Phase 3 demonstrated high level of consensus regarding the instrument's content relevance. This feasible and content-validated instrument shows potential for use in investigations of physiotherapy students' and physiotherapists' clinical reasoning, however continued development and testing are needed.

Automated discrimination of dementia spectrum disorders using extreme learning machine and structural T1 MRI features.

PubMed

Jongin Kim; Boreom Lee

2017-07-01

The classification of neuroimaging data for the diagnosis of Alzheimer's Disease (AD) is one of the main research goals of the neuroscience and clinical fields. In this study, we performed extreme learning machine (ELM) classifier to discriminate the AD, mild cognitive impairment (MCI) from normal control (NC). We compared the performance of ELM with that of a linear kernel support vector machine (SVM) for 718 structural MRI images from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The data consisted of normal control, MCI converter (MCI-C), MCI non-converter (MCI-NC), and AD. We employed SVM-based recursive feature elimination (RFE-SVM) algorithm to find the optimal subset of features. In this study, we found that the RFE-SVM feature selection approach in combination with ELM shows the superior classification accuracy to that of linear kernel SVM for structural T1 MRI data.

Neuroimaging features in subacute encephalopathy with seizures in alcoholics (SESA syndrome)

PubMed Central

Drake-Pérez, Marta; de Lucas, Enrique Marco; Lyo, John; Fernández-Torre, José L.

2017-01-01

Purpose To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). Methods We reviewed all cases reported previously, as well as 4 patients diagnosed in our center. We included a total of 8 patients. All subjects had clinical and EEG findings compatible with SESA syndrome and at least one MRI study that did not show other underlying condition that could be responsible for the clinical presentation. Results Initial MRI studies revealed the following features: cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion (6 patients), hyperperfusion (3 patients), atrophy (5 patients), chronic microvascular ischemic changes (4 patients). Follow-up MRI was performed in half of the patients, all showing a resolution of the hyperintense lesions, but developing focal atrophic changes in 75%. Conclusions SESA syndrome should be included among the alcohol-related encephalopathies. Its radiological features include transient cortical-subcortical T2-hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions. PMID:27391464

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, I.C.; Ko, S.F.; Shieh, C.S.

Ehlers-Danlos syndrome (EDS) includes a group of connective tissue disorders with abnormal collagen metabolism and a diverse clinical spectrum. We report two siblings with EDS who both presented with congenital diaphragmatic hernia (CDH). The elder sister suffered from recurrent diaphragmatic hernia twice and EDS was overlooked initially. Echocardiography as well as contrast-enhanced magnetic resonance angiography (MRA) showed dilatation of the pulmonary artery, and marked elongation and tortuosity of the aorta and its branches. A diagnosis of EDS was eventually established when these findings were coupled with the clinical features of hyperelastic skin. Her younger brother also had similar features. Thismore » report emphasizes that EDS may present as CDH in a small child which could easily be overlooked. Without appropriate surgery, diaphragmatic hernia might occur. Echocardiographic screening is recommended in patients with CDH. Contrast-enhanced MRA can be helpful in delineation of abnormally tortuous aortic great vessels that are an important clue to the early diagnosis of EDS.« less

The Knowledge Program: an Innovative, Comprehensive Electronic Data Capture System and Warehouse

PubMed Central

Katzan, Irene; Speck, Micheal; Dopler, Chris; Urchek, John; Bielawski, Kay; Dunphy, Cheryl; Jehi, Lara; Bae, Charles; Parchman, Alandra

2011-01-01

Data contained in the electronic health record (EHR) present a tremendous opportunity to improve quality-of-care and enhance research capabilities. However, the EHR is not structured to provide data for such purposes: most clinical information is entered as free text and content varies substantially between providers. Discrete information on patients’ functional status is typically not collected. Data extraction tools are often unavailable. We have developed the Knowledge Program (KP), a comprehensive initiative to improve the collection of discrete clinical information into the EHR and the retrievability of data for use in research, quality, and patient care. A distinct feature of the KP is the systematic collection of patient-reported outcomes, which is captured discretely, allowing more refined analyses of care outcomes. The KP capitalizes on features of the Epic EHR and utilizes an external IT infrastructure distinct from Epic for enhanced functionality. Here, we describe the development and implementation of the KP. PMID:22195124

Delirium and refeeding syndrome in anorexia nervosa.

PubMed

Norris, Mark L; Pinhas, Leora; Nadeau, Pierre-Olivier; Katzman, Debra K

2012-04-01

To review the literature on delirium and refeeding syndrome in patients with anorexia nervosa (AN) and present case examples in an attempt to identify common clinical features and response to therapy. A comprehensive literature review was completed. In addition to the cases identified in the literature, we present two additional cases of our own. We identified a total of 10 cases (all female; mean age 19 years old, range 12-29 years); 2/3 of the cases had similar clinical features predating the delirium and during refeeding. Delirium, albeit rare, can be associated with the refeeding syndrome in low weight patients with AN. During the initial refeeding phase, close monitoring of medical, metabolic, and psychological parameters are important in establishing factors that may elevate risk. Early detection and treatment of delirium using nonpharmacologic and pharmacologic means are also important to help minimize the effects of this potentially deadly condition. Copyright © 2011 Wiley Periodicals, Inc.

A family with Wagner syndrome with uveitis and a new versican mutation

PubMed Central

Rothschild, Pierre-Raphaël; Brézin, Antoine P.; Nedelec, Brigitte; des Roziers, Cyril Burin; Ghiotti, Tiffany; Orhant, Lucie; Boimard, Mathieu

2013-01-01

Purpose To report the clinical and molecular findings of a kindred with Wagner syndrome (WS) revealed by intraocular inflammatory features. Methods Eight available family members underwent complete ophthalmologic examination, including laser flare cell meter measurements. Collagen, type II, alpha 1, versican (VCAN), frizzled family receptor 4, low density lipoprotein receptor-related protein 5, tetraspanin 12, and Norrie disease (pseudoglioma) genes were screened with direct sequencing. Results The index case was initially referred for unexplained severe and chronic postoperative bilateral uveitis following a standard cataract surgery procedure. Clinical examination of the proband revealed an optically empty vitreous with avascular vitreous strands and veils, features highly suggestive of WS. The systematic familial ophthalmologic examination identified three additional unsuspected affected family members who also presented with the WS phenotype, including uveitis for one of them. We identified a novel c.4004–6T>A nucleotide substitution at the acceptor splice site of intron 7 of the VCAN gene that segregated with the disease phenotype. Conclusions We present a family with WS with typical WS features and intraocular inflammatory manifestations associated with a novel splice site VCAN mutation. Beyond the structural role in the retinal-vitreous architecture, versican is also emerging as a pivotal mediator of the inflammatory response, supporting uveitis predisposition as a clinical manifestation of WS. PMID:24174867

A family with Wagner syndrome with uveitis and a new versican mutation.

PubMed

Rothschild, Pierre-Raphaël; Brézin, Antoine P; Nedelec, Brigitte; Burin des Roziers, Cyril; Ghiotti, Tiffany; Orhant, Lucie; Boimard, Mathieu; Valleix, Sophie

2013-01-01

To report the clinical and molecular findings of a kindred with Wagner syndrome (WS) revealed by intraocular inflammatory features. Eight available family members underwent complete ophthalmologic examination, including laser flare cell meter measurements. Collagen, type II, alpha 1, versican (VCAN), frizzled family receptor 4, low density lipoprotein receptor-related protein 5, tetraspanin 12, and Norrie disease (pseudoglioma) genes were screened with direct sequencing. The index case was initially referred for unexplained severe and chronic postoperative bilateral uveitis following a standard cataract surgery procedure. Clinical examination of the proband revealed an optically empty vitreous with avascular vitreous strands and veils, features highly suggestive of WS. The systematic familial ophthalmologic examination identified three additional unsuspected affected family members who also presented with the WS phenotype, including uveitis for one of them. We identified a novel c.4004-6T>A nucleotide substitution at the acceptor splice site of intron 7 of the VCAN gene that segregated with the disease phenotype. We present a family with WS with typical WS features and intraocular inflammatory manifestations associated with a novel splice site VCAN mutation. Beyond the structural role in the retinal-vitreous architecture, versican is also emerging as a pivotal mediator of the inflammatory response, supporting uveitis predisposition as a clinical manifestation of WS.

Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein–Taybi and Filippi syndromes

PubMed Central

de Vries, Tamar I; R Monroe, Glen; van Belzen, Martine J; van der Lans, Christian A; Savelberg, Sanne MC; Newman, William G; van Haaften, Gijs; Nievelstein, Rutger A; van Haelst, Mieke M

2016-01-01

Rubinstein–Taybi syndrome (RTS, OMIM 180849) and Filippi syndrome (FLPIS, OMIM 272440) are both rare syndromes, with multiple congenital anomalies and intellectual deficit (MCA/ID). We present a patient with intellectual deficit, short stature, bilateral syndactyly of hands and feet, broad thumbs, ocular abnormalities, and dysmorphic facial features. These clinical features suggest both RTS and FLPIS. Initial DNA analysis of DNA isolated from blood did not identify variants to confirm either of these syndrome diagnoses. Whole-exome sequencing identified a homozygous variant in C9orf173, which was novel at the time of analysis. Further Sanger sequencing analysis of FLPIS cases tested negative for CKAP2L variants did not, however, reveal any further variants. Subsequent analysis using DNA isolated from buccal mucosa revealed a mosaic variant in CREBBP. This report highlights the importance of excluding mosaic variants in patients with a strong but atypical clinical presentation of a MCA/ID syndrome if no disease-causing variants can be detected in DNA isolated from blood samples. As the striking syndactyly observed in the present case is typical for FLPIS, we suggest CREBBP analysis in saliva samples for FLPIS syndrome cases in which no causal CKAP2L variant is detected. PMID:26956253

TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, H; Chen, W; Kligerman, S

2014-06-15

Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associatedmore » changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features including quantitative PET/CT features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer. This work was supported in part by National Cancer Institute Grant R21 CA131979 and R01 CA172638. Shan Tan was supported in part by the National Natural Science Foundation of China 60971112 and 61375018, and by Fundamental Research Funds for the Central Universities 2012QN086.« less

Rat Bite Fever and Streptobacillus moniliformis

PubMed Central

Elliott, Sean P.

2007-01-01

Rat bite fever, caused by Streptobacillus moniliformis, is a systemic illness classically characterized by fever, rigors, and polyarthralgias. If left untreated, it carries a mortality rate of 10%. Unfortunately, its nonspecific initial presentation combined with difficulties in culturing its causative organism produces a significant risk of delay or failure in diagnosis. The increasing popularity of rats and other rodents as pets, together with the risk of invasive or fatal disease, demands increased attention to rat bite fever as a potential diagnosis. The clinical and biological features of rat bite fever and Streptobacillus moniliformis are reviewed, providing some distinguishing features to assist the clinician and microbiologist in diagnosis. PMID:17223620

Nuclear Protein in Testis Carcinoma of the Thorax.

PubMed

Maruyama, Naomi; Hikiishi, Atsuhito; Suginaka, Miho; Furukawa, Koichi; Ogawa, Koichi; Nakamura, Naoki; Yoshida, Yae; Takata, Munetake; Nishijima, Masayoshi; Otani, Kenichiro; Kamimori, Takao; Fujiwara, Hiroshi; Yoshimatsu, Yuki; Ueda, Kayo

2018-06-06

Nuclear protein in testis (NUT) carcinoma (NUT-C) is an exceedingly rare and aggressive neoplasm. We herein report a case of a 57-year-old man with a rapidly progressing tumor of the thorax and left pleural effusion. The pathological features and immunohistochemical staining of specimens obtained by a transbronchial lung biopsy initially indicated poorly differentiated squamous cell carcinoma. However, given the clinical presentation along with the additional histopathologic features, NUT-C was considered. Immunohistochemical staining for NUT was positive in the pleural fluid cell block, confirming the diagnosis of NUT-C. This report indicates the utility of immunohistochemical staining for diagnosing NUT in the pleural fluid cell block.

Congenital renal rhabdoid tumor with placental metastases: immunohistochemistry, cytogenetic, and ultrastructural findings.

PubMed

de Tar, Michael; Sanford Biggerstaff, Julie

2006-01-01

Malignant congenital tumors of fetal origin are rare lesions, the most common type being congenital neuroblastoma. Although prenatal diagnosis is possible in large tumors, occasionally the tumor will be diagnosed first by its metastatic involvement of the placenta. Placental metastases can reflect either maternal or fetal primary sites, and each has relatively specific patterns of placental involvement. We describe the clinical and pathologic features of a widely metastatic congenital renal rhabdoid tumor with its placental and autopsy findings, and include the immunohistochemical, cytogenetic, and ultrastructural features. The pathologic features of the placenta in congenital renal rhabdoid tumor with placental metastasis have not been previously described. The examination of the placenta in this case led to the initial diagnosis and obviated the need for additional diagnostic procedures.

The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack.

PubMed

Hara, Naomi; Nishimura, Yukika; Yokoyama, Chika; Inoue, Ken; Nishida, Atsushi; Tanii, Hisashi; Okada, Motohiro; Kaiya, Hisanobu; Okazaki, Yuji

2012-04-11

The place where a patient experiences his/her first panic attack (FPA) may be related to their agoraphobia later in life. However, no investigations have been done into the clinical features according to the place where the FPA was experienced. In particular, there is an absence of detailed research examining patients who experienced their FPA at home. In this study, patients were classified by the location of their FPA and the differences in their clinical features were explored (e.g., symptoms of FPA, frequency of agoraphobia, and severity of FPA). The subjects comprised 830 panic disorder patients who were classified into 5 groups based on the place of their FPA (home, school/office, driving a car, in a public transportation vehicle, outside of home), The clinical features of these patients were investigated. Additionally, for panic disorder patients with agoraphobia at their initial clinic visit, the clinical features of patients who experienced their FPA at home were compared to those who experienced their attack elsewhere. In comparison of the FPAs of the 5 groups, significant differences were seen among the 7 descriptors (sex ratio, drinking status, smoking status, severity of the panic attack, depression score, ratio of agoraphobia, and degree of avoidance behavior) and 4 symptoms (sweating, chest pain, feeling dizzy, and fear of dying). The driving and public transportation group patients showed a higher incidence of co-morbid agoraphobia than did the other groups. Additionally, for panic disorder patients with co-morbid agoraphobia, the at-home group had a higher frequency of fear of dying compared to the patients in the outside-of-home group and felt more severe distress elicited by their FPA. The results of this study suggest that the clinical features of panic disorder patients vary according to the place of their FPA. The at-home group patients experienced "fear of dying" more frequently and felt more distress during their FPA than did the subjects in the other groups. These results indicate that patients experiencing their FPA at home should be treated with a focus on the fear and distress elicited by the attack.

The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack

PubMed Central

2012-01-01

Background The place where a patient experiences his/her first panic attack (FPA) may be related to their agoraphobia later in life. However, no investigations have been done into the clinical features according to the place where the FPA was experienced. In particular, there is an absence of detailed research examining patients who experienced their FPA at home. In this study, patients were classified by the location of their FPA and the differences in their clinical features were explored (e.g., symptoms of FPA, frequency of agoraphobia, and severity of FPA). Methods The subjects comprised 830 panic disorder patients who were classified into 5 groups based on the place of their FPA (home, school/office, driving a car, in a public transportation vehicle, outside of home), The clinical features of these patients were investigated. Additionally, for panic disorder patients with agoraphobia at their initial clinic visit, the clinical features of patients who experienced their FPA at home were compared to those who experienced their attack elsewhere. Results In comparison of the FPAs of the 5 groups, significant differences were seen among the 7 descriptors (sex ratio, drinking status, smoking status, severity of the panic attack, depression score, ratio of agoraphobia, and degree of avoidance behavior) and 4 symptoms (sweating, chest pain, feeling dizzy, and fear of dying). The driving and public transportation group patients showed a higher incidence of co-morbid agoraphobia than did the other groups. Additionally, for panic disorder patients with co-morbid agoraphobia, the at-home group had a higher frequency of fear of dying compared to the patients in the outside-of-home group and felt more severe distress elicited by their FPA. Conclusion The results of this study suggest that the clinical features of panic disorder patients vary according to the place of their FPA. The at-home group patients experienced "fear of dying" more frequently and felt more distress during their FPA than did the subjects in the other groups. These results indicate that patients experiencing their FPA at home should be treated with a focus on the fear and distress elicited by the attack. PMID:22494552

Vascular Physiology according to Clinical Scenario in Patients with Acute Heart Failure: Evaluation using the Cardio-Ankle Vascular Index.

PubMed

Goto, Toshihiko; Wakami, Kazuaki; Mori, Kento; Kikuchi, Shohei; Fukuta, Hidekatsu; Ohte, Nobuyuki

2016-09-01

Increased aortic stiffness may be an important cause of acute heart failure (AHF). Clinical scenario (CS), which classifies the pathophysiology of AHF based on the initial systolic blood pressure (sBP), was proposed to provide the most appropriate therapy for AHF patients. In CS, elevated aortic stiffness, vascular failure, has been considered as a feature of patients categorized as CS1 (sBP > 140 mmHg at initial presentation). However, whether elevated aortic stiffness, vascular failure, is present in such patients has not been fully elucidated. Therefore, we assessed aortic stiffness in AHF patients using the cardio-ankle vascular index (CAVI), which is considered to be independent of instantaneous blood pressure. Sixty-four consecutive AHF patients (mean age, 70.6 ± 12.8 years; 39 men) were classified with CS, based on their initial sBP: CS1: sBP > 140 mmHg (n = 29); CS2: sBP 100-140 mmHg (n = 22); and CS3: sBP < 100 mmHg (n = 13). There were significant group differences in CAVI (CS1 vs. CS2 vs. CS3: 9.7 ± 1.4 vs. 8.4 ± 1.7 vs. 8.3 ± 1.7, p = 0.006, analysis of variance). CAVI was significantly higher in CS1 than in CS2 (p = 0.02) and CS3 (p = 0.04). CAVI did not significantly correlate with sBP at the time of measurement of CAVI (r = 0.24 and p = 0.06). Aortic stiffness assessed using blood pressure-independent methodology apparently increased in CS1 AHF patients. We conclude that vascular failure is a feature of CS1 AHF initiation.

Pressure-Relief Features of Fixed and Autotitrating Continuous Positive Airway Pressure May Impair Their Efficacy: Evaluation with a Respiratory Bench Model

PubMed Central

Zhu, Kaixian; Aouf, Sami; Roisman, Gabriel; Escourrou, Pierre

2016-01-01

Study Objectives: Pressure-relief features are aimed at improving the patient's comfort during continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea. The objective of this study was to determine the effect of these therapy features on fixed CPAP and autotitrating CPAP (APAP) treatment efficacy. Methods: Seven pressure-relief features applied by three CPAP devices were included in our study (Remstar Auto: C-Flex 3, C-Flex+ 3, A-Flex 3, P-Flex; AirSense 10: EPR 3; Prisma 20A: SoftPAP 2 and 3). In fixed CPAP, the devices were subjected to a 10-min bench-simulated obstructive apnea sequence (initial apnea-hypopnea index, AHI = 60/h) with and without pressure-relief features. In APAP, the sequence was lengthened to 4.2 h (initial AHI = 58.6/h). The residual AHI and mean/median pressure were compared with and without pressure-relief features. Results: Compared to conventional CPAP, where pressure was adjusted to be just sufficient to control the simulated obstructive events, C-Flex+ 3, P-Flex, and EPR 3 failed to normalize the breathing flow and did not reduce the AHI. The mean pressures with the three features, respectively, were 1.8, 2.6, and 2.6 cmH2O lower than the conventional CPAP. Compared to conventional APAP, similar levels of control were observed with pressure-relief features, apart from P-Flex where the delivered mean pressure was lower and residual AHI greater. The device-reported mean/median pressures in APAP with A-Flex 3, P-Flex, EPR 3, and SoftPAP 3 were higher than that measured on the bench. Conclusions: Pressure-relief features may attenuate CPAP efficacy if not adjusted for at the time of their introduction. In clinical practice, efficacy can be ensured by increasing the therapeutic pressure delivered by fixed CPAP or by enabling the pressure-relief features prior to initial pressure titration. Device-reported pressures in APAP devices with pressure relief activated may overstate delivered pressures. Citation: Zhu K, Aouf S, Roisman G, Escourrou P. Pressure-relief features of fixed and autotitrating continuous positive airway pressure may impair their efficacy: evaluation with a respiratory bench model. J Clin Sleep Med 2016;12(3):385–392. PMID:26564383

Severe leptospirosis with multiple organ failure successfully treated by plasma exchange and high-volume hemofiltration.

PubMed

Bourquin, Vincent; Ponte, Belén; Hirschel, Bernard; Pugin, Jérôme; Martin, Pierre-Yves; Saudan, Patrick

2011-01-01

Background. Leptospirosis is a spirochetal zoonosis with complex clinical features including renal and liver failure. Case report. We report the case of a Swiss fisherman presenting with leptospirosis. After initial improvement, refractory septic shock and severe liver and kidney failure developed. The expected mortality was estimated at 90% with clinical scores. The patient underwent plasma exchanges and high-volume hemofiltration (HVHF) with complete recovery of hepatic and kidney functions. Discussion. Plasma exchanges and HVHF may confer survival benefit on patients with severe leptospirosis, refractory septic shock, and multiple-organ failure.

Heterotaxy syndrome with severe pulmonary hypertension in an adult.

PubMed

Brandenburg, Vincent M; Krueger, Stefan; Haage, Patrick; Mertens, Peter; Riehl, Jochen

2002-05-01

Heterotaxy syndrome is a rare clinical entity in adults, characterized by situs ambiguus, congenital heart defects, and splenic malformations. We report the case of an adult with heterotaxy syndrome (including situs ambiguus, bilateral superior vena cava, hypoplastic right-sided spleen and portosystemic shunts) presenting with dyspnea due to severe pulmonary hypertension. Vasodilatory therapy was initiated, leading to marked reduction of clinical symptoms. This case exhibits 2 particular and partially novel features: primary diagnosis of heterotaxy syndrome may be delayed until adulthood, and heterotaxy syndrome may be associated with pulmonary hypertension, possibly on the basis of longstanding portosystemic shunts.

[Paraneoplastic syndromes. Associated with lung cancer].

PubMed

Ochoa-Carrillo, Francisco Javier; Chávez-Mac Gregor, Mariana; Green-Renner, Dan; Green-Schneeweiss, León

2003-01-01

Paraneoplastic syndromes are disorders of host organ function occurring at a site remote from the primary tumor and its metastases. Paraneoplastic syndromes associated with primary lung cancer are not uncommon, have diverse initial manifestations, and epitomize the systemic nature of human malignant disease. The spectrum of clinical features in patients with paraneoplastic syndromes is very wide. Although diagnosis is often one of exclusion, improved understanding of the pathogenesis involved in some of these syndromes has provided another means of recognizing these disorders and perhaps treating affected patients. In this update, we review paraneoplastic syndromes associated with lung cancer, potential mechanisms, clinical manifestations, diagnosis, and treatment.

Tyrosine kinase gene rearrangements in epithelial malignancies

PubMed Central

Shaw, Alice T.; Hsu, Peggy P.; Awad, Mark M.; Engelman, Jeffrey A.

2014-01-01

Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as ‘druggable’ targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. PMID:24132104

Hyperthyroidism. Causes, clinical features, and diagnosis.

PubMed

Spaulding, S W; Lippes, H

1985-09-01

The usual patient with hyperthyroidism has Graves' disease: If serum levels of thyroid hormone are clearly elevated, the presence of infiltrative ophthalmopathy or pretibial myxedema is probably sufficient for establishing the diagnosis. However, if the ancillary findings of Graves' are not present, the radioactive iodine uptake should be determined to rule out other possible etiologies of hyperthyroidism. Signs of hyperthyroidism may be subtle or misleading, particularly in the elderly; the well-informed clinician keeps the diagnosis in mind, and if the initial thyroid hormone tests are not definitive, employs additional tests that are cost-effective in the individual clinical situation.

A Giant Heart Tumor in Neonate with Clinical Signs of Pierre - Robin Syndrome

PubMed Central

Bejiqi, Ramush; Retkoceri, Ragip; Xhema-Bejiqi, Hana; Bejiqi, Rinor; Maloku, Arlinda

2017-01-01

Introduction: Pierre Robin syndrome is a congenital condition of facial abnormalities in humans. The three main features are: cleft palate, retrognathia and glossoptosis. Rarely heart tumors are associated with syndromes, mostly are isolated. Case report: In this presentation we describe a 3-weeks-old girl with Pierre-Robin syndrome and giant left ventricle tumor, diagnosed initially by transthoracic echocardiography. The purpose of this report is to review the literature on the fetuses and neonates with cardiac tumors in an attempt to determine the various ways which cardiac tumors differ clinically and morphologically in this age group. PMID:28790548

A girl with West syndrome and autistic features harboring a de novo TBL1XR1 mutation.

PubMed

Saitsu, Hirotomo; Tohyama, Jun; Walsh, Tom; Kato, Mitsuhiro; Kobayashi, Yu; Lee, Ming; Tsurusaki, Yoshinori; Miyake, Noriko; Goto, Yu-Ichi; Nishino, Ichizo; Ohtake, Akira; King, Mary-Claire; Matsumoto, Naomichi

2014-10-01

Recently, de novo mutations in TBL1XR1 were found in two patients with autism spectrum disorders. Here, we report on a Japanese girl presenting with West syndrome, Rett syndrome-like and autistic features. Her initial development was normal until she developed a series of spasms at 5 months of age. Electroencephalogram at 7 months showed a pattern of hypsarrhythmia, which led to a diagnosis of West syndrome. Stereotypic hand movements appeared at 8 months of age, and autistic features such as deficits in communication, hyperactivity and excitability were observed later, at 4 years and 9 months. Whole exome sequencing of the patient and her parents revealed a de novo TBL1XR1 mutation [c.209 G>A (p.Gly70Asp)] occurring at an evolutionarily conserved amino acid in an F-box-like domain. Our report expands the clinical spectrum of TBL1XR1 mutations to West syndrome with Rett-like features, together with autistic features.

Thoracic sonography for pneumothorax: The clinical evaluation of an operational space medicine spin-off

NASA Astrophysics Data System (ADS)

Kirkpatrick, Andrew W.; Nicolaou, Savvas; Rowan, Kevin; Liu, David; Cunningham, Johan; Sargsyan, Ashot E.; Hamilton, Douglas; Dulchavsky, Scott A.

2005-05-01

The recent interest in the use of ultrasound (US) to detect pneumothoraces after acute trauma in North America was initially driven by an operational space medicine concern. Astronauts aboard the International Space Station (ISS) are at risk for pneumothoraces, and US is the only potential medical imaging available. Pneumothoraces are common following trauma, and are a preventable cause of death, as most are treatable with relatively simple interventions. While pneumothoraces are optimally diagnosed clinically, they are more often inapparent even on supine chest radiographs (CXR) with recent series reporting a greater than 50% rate of occult pneumothoraces. In the course of basic scientific investigations in a conventional and parabolic flight laboratory, investigators familiarized themselves with the sonographic features of both pneumothoraces and normal pulmonary ventilation. By examining the visceral-parietal pleural interface (VPPI) with US, investigators became confident in diagnosing pneumothoraces. This knowledge was subsequently translated into practice at an American and a Canadian trauma center. The sonographic examination was found to be more accurate and sensitive than CXR (US 96% and 100% versus US 74% and 36%) in specific circumstances. Initial studies have also suggested that detecting the US features of pleural pulmonary ventilation in the left lung field may offer the ability to exclude serious endotracheal tube malpositions such as right mainstem and esophageal intubations. Applied thoracic US is an example of a clinically useful space medicine spin-off that is improving health care on earth.

Clinical analysis of firework-related ocular injuries during Spring Festival 2009.

PubMed

Jing, Yuan; Yi-qiao, Xing; Yan-ning, Yang; Ming, Ai; An-huai, Yang; Lian-hong, Zhou

2010-03-01

To document the clinical features, management and visual outcome of fireworks-related ocular injuries during the Spring Festival. A retrospective analysis of all patients with fireworks-related ocular injuries attending the Department of Ophthalmology in Renmin Hospital of Wuhan University from January 20 to February 10, 2009. Age, gender, laterality, type of fireworks, location of incident, initial best-corrected visual acuity (BCVA), diagnosis, management, and final BCVA at last follow-up were documented. Relevant clinical features and visual outcome were evaluated. We observed 25 eyes in 24 patients. Injuries were more frequent in children (ten, 41.7%), males (19, 79.2%), and as open globe injury (15, 62.5%). The most common pyrotechnical products causing accidents were firecrackers (12, 50%). Rural residents had significantly higher rates of injury compared to urban residents (P = 0.023). Of 25 eyes, the most common injuries were corneal/scleral/corneoscleral open globe trauma (15, 60%), traumatic cataract (14, 56%), vitreous hemorrhage (seven, 28%) and retinal detachment (seven, 28%). Most eyes (23, 92%) received surgical intervention, including one (4%) eye enucleation. Vitrectomy was the most surgical treatment. After management, visual outcomes showed statistically significant improvement (P = 0.008). Initial BCVA correlated strongly with final BCVA (P = 0.010). Fireworks-related ocular injuries occur mainly in children, males and rural settings, are frequently severe and visually devastating. Therefore, preventive measures should be strengthened, including public education and legal restriction on the sale and use of fireworks.

Psychogenic Movement Disorders

PubMed Central

Morgante, Francesca; Edwards, Mark J.; Espay, Alberto J.

2013-01-01

Purpose of Review This review describes the main clinical features of psychogenic (functional) movement disorders and reports recent advances in diagnosis, pathophysiology, and treatment. Recent Findings The terminology and definition of patients with psychogenic movement disorders remain subjects of controversy; the term “functional” has been used more frequently in the literature in recent years regarding the neurobiological substrate underpinning these disorders. Correct diagnosis of psychogenic movement disorders should rely not on the exclusion of organic disorders or the sole presence of psychological factors but on the observation or elicitation of clinical features related to the specific movement disorder (ie, a positive or inclusionary rather than exclusionary diagnosis). Sudden onset, spontaneous remissions, and variability over time or during clinical examination are useful “red flags” suggestive of a psychogenic movement disorder. Imaging studies have demonstrated impaired connectivity between limbic and motor areas involved in movement programming and hypoactivity of a brain region that compares expected data with actual sensory data occurring during voluntary movement. Treatment of psychogenic movement disorders begins with ensuring the patient’s acceptance of the diagnosis during the initial debriefing and includes nonpharmacologic (cognitive-behavioral therapy, physiotherapy) and pharmacologic options. Summary Psychogenic movement disorders represent a challenging disorder for neurologists to diagnose and treat. Recent advances have increased understanding of the neurobiological mechanism of psychogenic movement disorders. Treatment with cognitive strategies and physical rehabilitation can benefit some patients. As short duration of disease correlates with better prognosis, early diagnosis and initiation of treatment are critical. PMID:24092294

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management.

PubMed

Grossmann, Mathis; Matsumoto, Alvin M

2017-03-01

Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic-pituitary-testicular axis pathology but have functional hypogonadism that is potentially reversible. Literature review from 1970 to October 2016. Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency-like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy.

Anatomical Features and Early Outcomes of Endovascular Repair of Abdominal Aortic Aneurysm from a Korean Multicenter Registry.

PubMed

Kwon, Hyunwook; Lee, Do Yun; Choi, Soo Jin Na; Park, Ki Hyuk; Min, Seung-Kee; Chang, Jeong-Hwan; Huh, Seung; Jeon, Yong Sun; Won, Jehwan; Byun, Seung Jae; Park, Sang Jun; Jang, Lee Chan; Kwon, Tae-Won

2015-09-01

To introduce a nation-based endovascular aneurysm repair (EVAR) registry in South Korea and to analyze the anatomical features and early clinical outcomes of abdominal aortic aneurysms (AAA) in patients who underwent EVAR. The Korean EVAR registry (KER) was a template-based online registry developed and established in 2009. The KER recruited 389 patients who underwent EVAR from 13 medical centers in South Korea from January 2010 to June 2010. We retrospectively reviewed the anatomic features and 30-day clinical outcomes. Initial deployment without open conversion was achieved in all cases and procedure-related 30-day mortality rate was 1.9%. Anatomic features showed the following variables: proximal aortic neck angle 48.8±25.7° (mean±standard deviation), vertical neck length 35.0±17.2 mm, aneurysmal sac diameter 57.2±14.2 mm, common iliac artery (CIA) involvement in 218 (56.3%) patients, and median right CIA length 34.9 mm. Two hundred and nineteen (56.3%) patients showed neck calcification, 98 patients (25.2%) had neck thrombus, and the inferior mesenteric arteries of 91 patients (23.4%) were occluded. Anatomical features of AAA in patients from the KER were characterized as having angulated proximal neck, tortuous iliac artery, and a higher rate of CIA involvement. Long-term follow-up and ongoing studies are required.

Uveitis profile and treatment response in Iranian patients with sarcoidosis.

PubMed

Mahmoudzadeh, Pouya; Tousi, Adib; Ramezani, Alireza; Soheilian, Roham; Soheilian, Masoud

2015-06-01

The aim of the study was to assess the clinical features and treatment responses in Iranian patients with sarcoid uveitis. A retrospective review of patients diagnosed with sarcoid uveitis from 1996 to 2010 was performed in a referral clinic in Tehran, Iran. Demographic and clinical features of patients, treatment modalities and therapeutic responses, and outcomes were recorded. Sixty-six eyes from 36 patients were studied. Twenty cases had biopsy-proven sarcoidosis. Mean duration of follow-up was 44.7 ± 45 months (range 3-175). Thirty-six eyes (54.5 %) had intermediate uveitis, 25 (37.9 %) panuveitis, and 5 (7.6 %) anterior uveitis. Twenty patients (55.5 %) responded to both systemic and/or topical corticosteroids, and 16 (44.4 %) required immunomodulatory drugs for control of uveitis. All of the patients finally responded to treatment in the form of inflammation reduction and/or vision improvement. The average time interval before initial clinical response following treatment was 3.2 ± 3 months (range 1-72). This study disclosed a higher predominance of females and intermediate form of uveitis in Iranian patients with sarcoid uveitis. Use of immunomodulatory drugs combined with corticosteroids resulted in good visual outcome and control of uveitis with a possible fewer corticosteroid side effects.

Familial early-onset dementia with tau intron 10 + 16 mutation with clinical features similar to those of Alzheimer disease.

PubMed

Doran, Mark; du Plessis, Daniel G; Ghadiali, Eric J; Mann, David M A; Pickering-Brown, Stuart; Larner, Andrew J

2007-10-01

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) owing to the tau intron 10 + 16 mutation usually occurs with a prototypical frontotemporal dementia phenotype with prominent disinhibition and affective disturbances. To report a new FTDP-17 pedigree with the tau intron 10 + 16 mutation demonstrating a clinical phenotype suggestive of Alzheimer disease. Case reports. Regional neuroscience centers in northwest England. Patients We examined 4 members of a kindred in which 8 individuals were affected in 3 generations. All 4 patients reported memory difficulty. Marked anomia was also present, but behavioral disturbances were conspicuously absent in the early stages of disease. All patients had an initial clinical diagnosis of Alzheimer disease. No mutations were found in the presenilin or amyloid precursor protein genes. Pathologic examination of the proband showed features typical of FTDP-17, and tau gene analysis showed the intron 10 + 16 mutation. This pedigree illustrates the phenotypic variability of tau intron 10 + 16 mutations. In pedigrees with a clinical diagnosis of Alzheimer disease but without presenilin or amyloid precursor protein gene mutations, tau gene mutations may be found.

If You Give a Nurse a Cookie: Sharing Teaching Strategies for Nurse Educator Development.

PubMed

Wingo, Nancy P

2017-01-01

Nurse educators often do not have time or a space to discuss ideas about effective teaching. To address this issue, an instructor at one school of nursing initiated Cookie Swap, a bimonthly, school-wide e-mail featuring stories about teaching strategies and tools used in face-to-face, online, and clinical courses. J Contin Educ Nurs. 2017;48(1):12-13. Copyright 2017, SLACK Incorporated.

Conversion of pemphigoid gestationis to bullous pemphigoid--two refractory cases highlighting this association.

PubMed

Jenkins, R E; Jones, S A; Black, M M

1996-10-01

Pemphigoid gestationis and bullous pemphigoid are autoimmune diseases characterized by subepidermal blisters and antibodies against the hemidesmosomal antigens: BPAG1 and BPAG2. Clinical histological and immunological similarities between pemphigoid gestationis and bullous pemphigoid suggest that they may have common pathogenetic determinants. We report two patients who presented initially with clinico-pathological features characteristic of pemphigoid gestationis but who subsequently evolved into bullous pemphigoid.

Automated image processing and analysis of cartilage MRI: enabling technology for data mining applied to osteoarthritis

PubMed Central

Tameem, Hussain Z.; Sinha, Usha S.

2011-01-01

Osteoarthritis (OA) is a heterogeneous and multi-factorial disease characterized by the progressive loss of articular cartilage. Magnetic Resonance Imaging has been established as an accurate technique to assess cartilage damage through both cartilage morphology (volume and thickness) and cartilage water mobility (Spin-lattice relaxation, T2). The Osteoarthritis Initiative, OAI, is a large scale serial assessment of subjects at different stages of OA including those with pre-clinical symptoms. The electronic availability of the comprehensive data collected as part of the initiative provides an unprecedented opportunity to discover new relationships in complex diseases such as OA. However, imaging data, which provides the most accurate non-invasive assessment of OA, is not directly amenable for data mining. Changes in morphometry and relaxivity with OA disease are both complex and subtle, making manual methods extremely difficult. This chapter focuses on the image analysis techniques to automatically localize the differences in morphometry and relaxivity changes in different population sub-groups (normal and OA subjects segregated by age, gender, and race). The image analysis infrastructure will enable automatic extraction of cartilage features at the voxel level; the ultimate goal is to integrate this infrastructure to discover relationships between the image findings and other clinical features. PMID:21785520

Chest radiographic characteristics of community-acquired Legionella pneumonia in the elderly.

PubMed

Zhang, Zhigang; Liu, Xinmin; Chen, Luzeng; Qiu, Jianxing

2014-01-01

Legionella is an important community-acquired pneumonia pathogen. Although the elderly are especially susceptible to Legionella, few studies have looked at comparative radiographic features of Legionella pneumonia in this population. The aim of this study was to explore the chest radiographic characteristics of community-acquired Legionella pneumonia in the elderly. Serial chest radiographs obtained in 34 patients hospitalized with serologically proven Legionella pneumonia were retrospectively reviewed. Chest X-ray features of an aged group of ≥ 65 years were assessed and compared with a non-aged group of <65 years old with regard to initial patterns and distributions of pulmonary abnormalities, accompanying signs, and progression. The most common initial presentation was a patchy alveolar infiltrate involving a single lobe, most often the lower lobe. There was no middle or lingular lobe involvement in the aged group patients, but bilateral pleural effusion was significantly more common in this group. In the aged group patients, radiographic progression following adequate therapy, despite a clinical response, was more often noted and the radiographs were less likely to have returned to the premorbid state at discharge, but the differences were not significant between the two groups. The discrepancy between imaging findings and clinical symptoms seems more prominent in community-acquired Legionella pneumonia in the elderly.

Automated image processing and analysis of cartilage MRI: enabling technology for data mining applied to osteoarthritis

NASA Astrophysics Data System (ADS)

Tameem, Hussain Z.; Sinha, Usha S.

2007-11-01

Osteoarthritis (OA) is a heterogeneous and multi-factorial disease characterized by the progressive loss of articular cartilage. Magnetic Resonance Imaging has been established as an accurate technique to assess cartilage damage through both cartilage morphology (volume and thickness) and cartilage water mobility (Spin-lattice relaxation, T2). The Osteoarthritis Initiative, OAI, is a large scale serial assessment of subjects at different stages of OA including those with pre-clinical symptoms. The electronic availability of the comprehensive data collected as part of the initiative provides an unprecedented opportunity to discover new relationships in complex diseases such as OA. However, imaging data, which provides the most accurate non-invasive assessment of OA, is not directly amenable for data mining. Changes in morphometry and relaxivity with OA disease are both complex and subtle, making manual methods extremely difficult. This chapter focuses on the image analysis techniques to automatically localize the differences in morphometry and relaxivity changes in different population sub-groups (normal and OA subjects segregated by age, gender, and race). The image analysis infrastructure will enable automatic extraction of cartilage features at the voxel level; the ultimate goal is to integrate this infrastructure to discover relationships between the image findings and other clinical features.

Meeting the challenges of clinical information provision.

PubMed

Spring, Hannah

2017-12-01

This virtual issue of the Health Information and Libraries Journal (HILJ) has been compiled to mark the 5th International Clinical Librarian Conference 2011. In considering the challenges of clinical information provision, the content selected for the virtual issue offers an international flavour of clinical information provision and covers a variety of different facets of clinical librarianship. The issue broadly covers the areas of information needs and preferences, clinical librarian roles and services, and education and training, and reflects the way in which a normal issue of the HILJ would be presented. This includes a review article, a collection of original articles, and the three regular features which comprise International Perspectives and Initiatives, Learning and Teaching in Action, and Using Evidence in Practice. All papers included in this virtual issue are available free online. © 2011 The authors. Health Information and Libraries Journal © 2011 Health Libraries Group.

Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue.

PubMed

Mitra, Shubhanker; Gautam, Ira; Jambugulam, Mohan; Abhilash, Kundavaram Paul Prabhakar; Jayaseeelan, Vishalakshi

2017-01-01

Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (<4000, 4001-7000 and >7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (<2 and ≥2 mg/dL), serum glutamic oxaloacetic transaminase (>200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79-0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. In areas of high burden of ST and dengue, model 2 (the "clinical score to differentiate scrub typhus and dengue fever") is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

Fat embolism syndrome in long bone trauma following vehicular accidents: Experience from a tertiary care hospital in north India.

PubMed

Koul, Parvaiz A; Ahmad, Feroze; Gurcoo, Showkat A; Khan, Umar H; Naqash, Imtiyaz A; Sidiq, Suhail; Jan, Rafi Ahmad; Koul, Ajaz N; Ashraf, Mohammad; Bhat, Mubasher Ahmad

2013-04-01

Fat embolism syndrome (FES) is a clinical problem arising mainly due to fractures particularly of long bones and pelvis. Not much literature is available about FES from the Indian subcontinent. Thirty-five patients referred/admitted prospectively over a 3-year period for suspected FES to a north Indian tertiary care center and satisfying the clinical criteria proposed by Gurd and Wilson, and Schonfeld were included in the study. Clinical features, risk factors, complications, response to treatment and any sequelae were recorded. The patients (all male) presented with acute onset breathlessness, 36-120 hours following major bone trauma due to vehicular accidents. Associated features included features of cerebral dysfunction (n = 24, 69%), petechial rash (14%), tachycardia (94%) and fever (46%). Hypoxemia was demonstrable in 80% cases, thrombocytopenia in 91%, anemia in 94% and hypoalbuminemia in 59%. Bilateral alveolar infiltrates were seen on chest radiography in 28 patients and there was evidence of bilateral ground glass appearance in 5 patients on CT. Eleven patients required ventilatory assistance whereas others were treated with supportive management. Three patients expired due to associated sepsis and respiratory failure, whereas others recovered with a mean hospital stay of 9 days. No long term sequelae were observed. FES remains a clinical challenge and is a diagnosis of exclusion based only on clinical grounds because of the absence of any specific laboratory test. A high index of suspicion is required for diagnosis and initiating supportive management in patients with traumatic fractures, especially in those having undergone an invasive orthopedic procedure.

Fat embolism syndrome in long bone trauma following vehicular accidents: Experience from a tertiary care hospital in north India

PubMed Central

Koul, Parvaiz A.; Ahmad, Feroze; Gurcoo, Showkat A.; Khan, Umar H.; Naqash, Imtiyaz A.; Sidiq, Suhail; Jan, Rafi Ahmad; Koul, Ajaz N.; Ashraf, Mohammad; Bhat, Mubasher Ahmad

2013-01-01

Background: Fat embolism syndrome (FES) is a clinical problem arising mainly due to fractures particularly of long bones and pelvis. Not much literature is available about FES from the Indian subcontinent. Materials and Methods: Thirty-five patients referred/admitted prospectively over a 3-year period for suspected FES to a north Indian tertiary care center and satisfying the clinical criteria proposed by Gurd and Wilson, and Schonfeld were included in the study. Clinical features, risk factors, complications, response to treatment and any sequelae were recorded. Results: The patients (all male) presented with acute onset breathlessness, 36-120 hours following major bone trauma due to vehicular accidents. Associated features included features of cerebral dysfunction (n = 24, 69%), petechial rash (14%), tachycardia (94%) and fever (46%). Hypoxemia was demonstrable in 80% cases, thrombocytopenia in 91%, anemia in 94% and hypoalbuminemia in 59%. Bilateral alveolar infiltrates were seen on chest radiography in 28 patients and there was evidence of bilateral ground glass appearance in 5 patients on CT. Eleven patients required ventilatory assistance whereas others were treated with supportive management. Three patients expired due to associated sepsis and respiratory failure, whereas others recovered with a mean hospital stay of 9 days. No long term sequelae were observed. Conclusion: FES remains a clinical challenge and is a diagnosis of exclusion based only on clinical grounds because of the absence of any specific laboratory test. A high index of suspicion is required for diagnosis and initiating supportive management in patients with traumatic fractures, especially in those having undergone an invasive orthopedic procedure. PMID:23741088

Clinical Features of Pregnancy-associated Retinal and Choroidal Diseases Causing Acute Visual Disturbance.

PubMed

Park, Young Joo; Park, Kyu Hyung; Woo, Se Joon

2017-08-01

To report clinical features of patients with retinal and choroidal diseases presenting with acute visual disturbance during pregnancy. In this retrospective case series, patients who developed acute visual loss during pregnancy (including puerperium) and visited a tertiary hospital from July 2007 to June 2015, were recruited by searching electronic medical records. Patients were categorized according to the cause of visual loss. Clinical features and required diagnostic modalities were analyzed in the retinal and choroidal disease group. Acute visual loss occurred in 147 patients; 49 (38.9%) were classified into the retinal and choroidal group. The diagnoses included central serous chorioretinopathy (22.4%), hypertensive retinopathy with or without pre-eclampsia (22.4%), retinal tear with or without retinal detachment (18.4%), diabetic retinopathy progression (10.2%), Vogt-Koyanagi-Harada disease (4.1%), retinal artery occlusion (4.1%), multiple evanescent white dot syndrome (4.1%), and others (14.3%). Visual symptoms first appeared at gestational age 25.9 ± 10.3 weeks. The initial best-corrected visual acuity (BCVA) was 0.27 ± 0.39 logarithm of the minimum angle of resolution (logMAR); the final BCVA after delivery improved to 0.13 ± 0.35 logMAR. Serious visual deterioration (BCVA worth than 20 / 200) developed in two patients. Differential diagnoses were established with characteristic fundus and spectral-domain optical coherence tomography findings in all cases. In pregnant women with acute visual loss, retinal and choroidal diseases are common and could be vision threatening. Physicians should be aware of pregnancy-associated retinal and choroidal diseases and their clinical features. The differential diagnosis can be established with non-invasive techniques. © 2017 The Korean Ophthalmological Society

Lesion with morphologic feature of organizing pneumonia (OP) in CT-guided lung biopsy samples for diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP): a retrospective study of 134 cases in a single center.

PubMed

Miao, Liyun; Wang, Yongsheng; Li, Yan; Ding, Jingjing; Chen, Lulu; Dai, Jinghong; Cai, Hourong; Xiao, Yonglong; Cao, Min; Huang, Mei; Qiu, Yuying; Meng, Fanqing; Fan, Xiangshan; Zhang, Deping; Song, Yong

2014-09-01

Small biopsy samples are generally considered inconclusive for bronchiolitis obliterans organizing pneumonia (BOOP) diagnosis despite their potential to reveal organizing pneumonia (OP) pathologically, necessitating risky invasive tissue biopsy during surgery for reliable confirmation. OP by CT-guided lung biopsy was to evaluate the role in the diagnosis of BOOP. A retrospective review of 134 cases with the OP feature in the CT-guided lung biopsy samples between 2004 and 2011 at a single center was conducted. Diagnostic accuracy of OP by CT-guided lung biopsy and clinical-radiographic data alone were compared. After exclusion of 11 cases due to pathology with others besides OP and 15 cases for loss to follow-up, 108 were included. Of these, 95 cases and 13 cases were classified as BOOP and non-BOOP group, respectively. Among BOOP group, only 30 were initially diagnosed as BOOP according to the typical clinical and radiographic features. The other 65 cases with atypical features were diagnosed as BOOP mainly based on OP by CT-guided lung biopsy. Among non-BOOP group, one was misdiagnosed as BOOP, and others were not BOOP according to clinical and radiographic findings. Thus, OP by CT-guided lung biopsy produced a diagnostic accuracy of 87.96% (95/108), much higher than 31.25% (30/96) observed using clinical and radiographic data alone. Combined, these techniques produced diagnostic accuracy of 98.96% (95/96). OP by CT-guided lung biopsy can be effectively used as the pathological evidence for BOOP diagnosis and reducing unnecessary surgery.

Lesion with morphologic feature of organizing pneumonia (OP) in CT-guided lung biopsy samples for diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP): a retrospective study of 134 cases in a single center

PubMed Central

Wang, Yongsheng; Li, Yan; Ding, Jingjing; Chen, Lulu; Dai, Jinghong; Cai, Hourong; Xiao, Yonglong; Cao, Min; Huang, Mei; Qiu, Yuying; Meng, Fanqing; Fan, Xiangshan; Zhang, Deping

2014-01-01

Background Small biopsy samples are generally considered inconclusive for bronchiolitis obliterans organizing pneumonia (BOOP) diagnosis despite their potential to reveal organizing pneumonia (OP) pathologically, necessitating risky invasive tissue biopsy during surgery for reliable confirmation. Objective OP by CT-guided lung biopsy was to evaluate the role in the diagnosis of BOOP. Methods A retrospective review of 134 cases with the OP feature in the CT-guided lung biopsy samples between 2004 and 2011 at a single center was conducted. Diagnostic accuracy of OP by CT-guided lung biopsy and clinical-radiographic data alone were compared. Results After exclusion of 11 cases due to pathology with others besides OP and 15 cases for loss to follow-up, 108 were included. Of these, 95 cases and 13 cases were classified as BOOP and non-BOOP group, respectively. Among BOOP group, only 30 were initially diagnosed as BOOP according to the typical clinical and radiographic features. The other 65 cases with atypical features were diagnosed as BOOP mainly based on OP by CT-guided lung biopsy. Among non-BOOP group, one was misdiagnosed as BOOP, and others were not BOOP according to clinical and radiographic findings. Thus, OP by CT-guided lung biopsy produced a diagnostic accuracy of 87.96% (95/108), much higher than 31.25% (30/96) observed using clinical and radiographic data alone. Combined, these techniques produced diagnostic accuracy of 98.96% (95/96). Conclusions OP by CT-guided lung biopsy can be effectively used as the pathological evidence for BOOP diagnosis and reducing unnecessary surgery. PMID:25276367

Characteristics of Cytomegalovirus Uveitis in Immunocompetent Patients.

PubMed

Woo, Jyh Haur; Lim, Wee K; Ho, Su L; Teoh, Stephen C

2015-01-01

To present the clinical characteristics of patients with anterior uveitis who had evidence of cytomegalovirus (CMV) infection on polymerase chain reaction PCR-based assays for viral DNA in aqueous samples. This was a retrospective observational case series of 16 patients with CMV infection on qualitative polymerase chain reaction PCR-based assays for viral DNA in aqueous samples. Case records of 16 patients were reviewed and relevant clinical information was collected using a standardized data sheet. There were 10 male and 6 female patients, with 16 eyes included. The median age at the first attack was 52 years (range 27-77 years). Thirteen patients (81.3%) presented with an initial BCVA of 20/40 or better. Eleven eyes (68.8%) had anterior chamber inflammation of 1+ cells or less. Eight eyes (50.0%) had concomitant sectoral iris atrophy, while 2 eyes were noted to have heterochromic irides. Eleven patients (68.8%) presented with an elevated intraocular pressure. Seven patients (43.8%) had clinical features that led to a presumptive diagnosis of Posner-Schlossman syndrome, while 3 patients (18.8%) were initially diagnosed with Fuchs heterochromic iridocyclitis. Six patients were initially treated for uveitic glaucoma or anterior uveitis of unknown cause. There is a spectrum of clinical manifestations of CMV anterior uveitis. A high index of suspicion of a possible viral etiology, especially CMV, and subsequent accurate identification of the virus involved are fundamental to the overall therapeutic approach.

STUMP un"stumped": anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion.

PubMed

Subbiah, Vivek; McMahon, Caitlin; Patel, Shreyaskumar; Zinner, Ralph; Silva, Elvio G; Elvin, Julia A; Subbiah, Ishwaria M; Ohaji, Chimela; Ganeshan, Dhakshina Moorthy; Anand, Deepa; Levenback, Charles F; Berry, Jenny; Brennan, Tim; Chmielecki, Juliann; Chalmers, Zachary R; Mayfield, John; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S; Ali, Siraj M

2015-06-11

Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options. To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein. Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage. Therapy was given in the context of a phase I clinical trial ClinicalTrials.gov Identifier: ( NCT01548144 ). Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion. The diagnosis of STUMP was revised to that of an IMT with myxoid features. The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®). The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 1.1 criteria. For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities.

Large-scale feature searches of collections of medical imagery

NASA Astrophysics Data System (ADS)

Hedgcock, Marcus W.; Karshat, Walter B.; Levitt, Tod S.; Vosky, D. N.

1993-09-01

Large scale feature searches of accumulated collections of medical imagery are required for multiple purposes, including clinical studies, administrative planning, epidemiology, teaching, quality improvement, and research. To perform a feature search of large collections of medical imagery, one can either search text descriptors of the imagery in the collection (usually the interpretation), or (if the imagery is in digital format) the imagery itself. At our institution, text interpretations of medical imagery are all available in our VA Hospital Information System. These are downloaded daily into an off-line computer. The text descriptors of most medical imagery are usually formatted as free text, and so require a user friendly database search tool to make searches quick and easy for any user to design and execute. We are tailoring such a database search tool (Liveview), developed by one of the authors (Karshat). To further facilitate search construction, we are constructing (from our accumulated interpretation data) a dictionary of medical and radiological terms and synonyms. If the imagery database is digital, the imagery which the search discovers is easily retrieved from the computer archive. We describe our database search user interface, with examples, and compare the efficacy of computer assisted imagery searches from a clinical text database with manual searches. Our initial work on direct feature searches of digital medical imagery is outlined.

Relationship between atypical depression and social anxiety disorder.

PubMed

Koyuncu, Ahmet; Ertekin, Erhan; Ertekin, Banu Aslantaş; Binbay, Zerrin; Yüksel, Çağrı; Deveci, Erdem; Tükel, Raşit

2015-01-30

In this study, we aimed to investigate the effects of atypical and non-atypical depression comorbidity on the clinical characteristics and course of social anxiety disorder (SAD). A total of 247 patients with SAD were enrolled: 145 patients with a current depressive episode (unipolar or bipolar) with atypical features, 43 patients with a current depressive episode with non-atypical features and 25 patients without a lifetime history of depressive episodes were compared regarding sociodemographic and clinical features, comorbidity rates, and severity of SAD, depression and functional impairment. Thirty four patients with a past but not current history of major depressive episodes were excluded from the comparisons. 77.1% of current depressive episodes were associated with atypical features. Age at onset of SAD and age at initial major depressive episode were lower in the group with atypical depression than in the group with non-atypical depression. History of suicide attempts and bipolar disorder comorbidity was more common in the atypical depression group as well. Atypical depression group has higher SAD and depression severity and lower functionality than group with non-atypical depression. Our results indicate that the presence of atypical depression is associated with more severe symptoms and more impairment in functioning in patients with SAD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Phenomenology and classification of dystonia: a consensus update

PubMed Central

Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B.; DeLong, Mahlon R.; Fahn, Stanley; Fung, Victor S.C.; Hallett, Mark; Jankovic, Joseph; Jinnah, H.A.; Klein, Christine; Lang, Anthony E.; Mink, Jonathan W.; Teller, Jan K.

2013-01-01

This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during three in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along two axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features), and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. PMID:23649720

An information management system for patients with tuberculosis: usability assessment with end-users.

PubMed

Darby, Jonathan; Black, Jim; Morrison, David; Buising, Kirsty

2012-01-01

Information systems with clinical decision support (CDS) offer great potential to assist the co-ordination of patients with chronic diseases and to improve patient care. Despite this, few have entered routine clinical use. Tuberculosis (TB) is an infection of public health importance. It has complex interactions with many comorbid conditions, requires close supervised care and prolonged treatment for effective cure. These features make it suitable for use with an information management system with CDS features. In close consultation with key stakeholders, a clinical application was developed for the management of TB patients in Victoria. A formal usability assessment using semi-structured case-scenario based exercises was performed. Subjects were 12 individuals closely involved in the care of TB patients, including Infectious Diseases and Respiratory Physicians, and Public Health Nurses. Two researchers conducted the sessions, independently analysed responses and discrepancies compared to the voice record for validity. Despite varied computer experience, responses were positive regarding user interface and content. Data location was not always intuitive, however this improved with familiarity of the program. Decision support was considered valuable, with useful suggestions for expansion of these features. Automated reporting for correspondence and notification to the Health Department were felt worth the initial investment in data entry. An important workflow-based issue regarding dismissal of alerts and several errors were detected. Usability assessment validated many design elements of the system, provided a unique insight into workflow issues faced by users and hopefully will impact on its ultimate clinical utility.

Unusual echocardiographic features seen in a case of giant cell myocarditis

PubMed Central

Kochar, Minisha; López-Candales, Angel; Ramani, Gautam; Rajagopalan, Navin; Edelman, Kathy

2008-01-01

The case of an 18-year-old college football player with a recent history of streptococcal pharyngitis who was experiencing progressive disabling dyspnea on exertion with easy fatigability and lack of stamina, and was taken to the hospital after a syncopal episode is described. The patient was initially diagnosed with heart failure and treated accordingly. However, because of a fulminant clinical deterioration, an endomyocardial biopsy was recommended, which showed focal giant cell transformation consistent with giant cell myocarditis. Treatment with methylprednisolone and cyclosporine was promptly initiated. Several apical clots were noted during treatment, but the patient attained full recovery with treatment. PMID:18987760

Unusual echocardiographic features seen in a case of giant cell myocarditis.

PubMed

Kochar, Minisha; López-Candales, Angel; Ramani, Gautam; Rajagopalan, Navin; Edelman, Kathy

2008-11-01

The case of an 18-year-old college football player with a recent history of streptococcal pharyngitis who was experiencing progressive disabling dyspnea on exertion with easy fatigability and lack of stamina, and was taken to the hospital after a syncopal episode is described. The patient was initially diagnosed with heart failure and treated accordingly. However, because of a fulminant clinical deterioration, an endomyocardial biopsy was recommended, which showed focal giant cell transformation consistent with giant cell myocarditis. Treatment with methylprednisolone and cyclosporine was promptly initiated. Several apical clots were noted during treatment, but the patient attained full recovery with treatment.

Predictive value of initial FDG-PET features for treatment response and survival in esophageal cancer patients treated with chemo-radiation therapy using a random forest classifier.

PubMed

Desbordes, Paul; Ruan, Su; Modzelewski, Romain; Pineau, Pascal; Vauclin, Sébastien; Gouel, Pierrick; Michel, Pierre; Di Fiore, Frédéric; Vera, Pierre; Gardin, Isabelle

2017-01-01

In oncology, texture features extracted from positron emission tomography with 18-fluorodeoxyglucose images (FDG-PET) are of increasing interest for predictive and prognostic studies, leading to several tens of features per tumor. To select the best features, the use of a random forest (RF) classifier was investigated. Sixty-five patients with an esophageal cancer treated with a combined chemo-radiation therapy were retrospectively included. All patients underwent a pretreatment whole-body FDG-PET. The patients were followed for 3 years after the end of the treatment. The response assessment was performed 1 month after the end of the therapy. Patients were classified as complete responders and non-complete responders. Sixty-one features were extracted from medical records and PET images. First, Spearman's analysis was performed to eliminate correlated features. Then, the best predictive and prognostic subsets of features were selected using a RF algorithm. These results were compared to those obtained by a Mann-Whitney U test (predictive study) and a univariate Kaplan-Meier analysis (prognostic study). Among the 61 initial features, 28 were not correlated. From these 28 features, the best subset of complementary features found using the RF classifier to predict response was composed of 2 features: metabolic tumor volume (MTV) and homogeneity from the co-occurrence matrix. The corresponding predictive value (AUC = 0.836 ± 0.105, Se = 82 ± 9%, Sp = 91 ± 12%) was higher than the best predictive results found using the Mann-Whitney test: busyness from the gray level difference matrix (P < 0.0001, AUC = 0.810, Se = 66%, Sp = 88%). The best prognostic subset found using RF was composed of 3 features: MTV and 2 clinical features (WHO status and nutritional risk index) (AUC = 0.822 ± 0.059, Se = 79 ± 9%, Sp = 95 ± 6%), while no feature was significantly prognostic according to the Kaplan-Meier analysis. The RF classifier can improve predictive and prognostic values compared to the Mann-Whitney U test and the univariate Kaplan-Meier survival analysis when applied to several tens of features in a limited patient database.

Learning to detect vocal hyperfunction from ambulatory neck-surface acceleration features: initial results for vocal fold nodules.

PubMed

Ghassemi, Marzyeh; Van Stan, Jarrad H; Mehta, Daryush D; Zañartu, Matías; Cheyne, Harold A; Hillman, Robert E; Guttag, John V

2014-06-01

Voice disorders are medical conditions that often result from vocal abuse/misuse which is referred to generically as vocal hyperfunction. Standard voice assessment approaches cannot accurately determine the actual nature, prevalence, and pathological impact of hyperfunctional vocal behaviors because such behaviors can vary greatly across the course of an individual's typical day and may not be clearly demonstrated during a brief clinical encounter. Thus, it would be clinically valuable to develop noninvasive ambulatory measures that can reliably differentiate vocal hyperfunction from normal patterns of vocal behavior. As an initial step toward this goal we used an accelerometer taped to the neck surface to provide a continuous, noninvasive acceleration signal designed to capture some aspects of vocal behavior related to vocal cord nodules, a common manifestation of vocal hyperfunction. We gathered data from 12 female adult patients diagnosed with vocal fold nodules and 12 control speakers matched for age and occupation. We derived features from weeklong neck-surface acceleration recordings by using distributions of sound pressure level and fundamental frequency over 5-min windows of the acceleration signal and normalized these features so that intersubject comparisons were meaningful. We then used supervised machine learning to show that the two groups exhibit distinct vocal behaviors that can be detected using the acceleration signal. We were able to correctly classify 22 of the 24 subjects, suggesting that in the future measures of the acceleration signal could be used to detect patients with the types of aberrant vocal behaviors that are associated with hyperfunctional voice disorders.

Skin depigmentation associated with toceranib phosphate in a dog.

PubMed

Cavalcanti, Jacqueline V J; Hasbach, Andrea; Barnes, Katie; Dange, Rahul B; Patterson, Jon; Saavedra, Paulo Vilar

2017-08-01

Drug-induced depigmentation is frequently observed in humans undergoing tyrosine kinase inhibitor therapy, whereas it is not reported in dogs. The skin depigmentation can occur after the first week of treatment and it is reversible within a few weeks after drug discontinuation. To report the clinical and histopathological features of an episode of cutaneous adverse drug reaction associated with short term administration of toceranib phosphate. An 11-year-old intact male Bernese mountain dog was presented for investigation of a subcutaneous mast cell tumour (MCT) including treatment options. The major abnormality on physical examination was a 7.5 × 10 cm subcutaneous mass located cranial to the left shoulder joint consistent with a MCT. Toceranib phosphate therapy was initiated. Fourteen days after initiating treatment, the dog presented with skin erosions near the lateral canthus of the left eye. Three weeks later there were multiple skin lesions characterized by alopecia and depigmentation involving left and right eyelids; leukotrichia of the periorbital areas and depigmentation of the nasal planum and all paw pads. Histopathological findings were nonspecific; they were supportive of vitiligo. Resolution of skin lesions was observed after stopping the toceranib phosphate therapy. Based on the gross lesions, histopathological features before and after tyrosine kinase inhibitor therapy, and Naranjo score, this case was considered to be consistent with cutaneous adverse drug effects. To the best of the authors' knowledge, this is the first report describing the clinical and histopathological features of presumed drug-induced skin depigmentation in a dog receiving toceranib phosphate. © 2017 ESVD and ACVD.

Stochastic formulation of patient positioning using linac-mounted cone beam imaging with prior knowledge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoegele, W.; Loeschel, R.; Dobler, B.

2011-02-15

Purpose: In this work, a novel stochastic framework for patient positioning based on linac-mounted CB projections is introduced. Based on this formulation, the most probable shifts and rotations of the patient are estimated, incorporating interfractional deformations of patient anatomy and other uncertainties associated with patient setup. Methods: The target position is assumed to be defined by and is stochastically determined from positions of various features such as anatomical landmarks or markers in CB projections, i.e., radiographs acquired with a CB-CT system. The patient positioning problem of finding the target location from CB projections is posed as an inverse problem withmore » prior knowledge and is solved using a Bayesian maximum a posteriori (MAP) approach. The prior knowledge is three-fold and includes the accuracy of an initial patient setup (such as in-room laser and skin marks), the plasticity of the body (relative shifts between target and features), and the feature detection error in CB projections (which may vary depending on specific detection algorithm and feature type). For this purpose, MAP estimators are derived and a procedure of using them in clinical practice is outlined. Furthermore, a rule of thumb is theoretically derived, relating basic parameters of the prior knowledge (initial setup accuracy, plasticity of the body, and number of features) and the parameters of CB data acquisition (number of projections and accuracy of feature detection) to the expected estimation accuracy. Results: MAP estimation can be applied to arbitrary features and detection algorithms. However, to experimentally demonstrate its applicability and to perform the validation of the algorithm, a water-equivalent, deformable phantom with features represented by six 1 mm chrome balls were utilized. These features were detected in the cone beam projections (XVI, Elekta Synergy) by a local threshold method for demonstration purposes only. The accuracy of estimation (strongly varying for different plasticity parameters of the body) agreed with the rule of thumb formula. Moreover, based on this rule of thumb formula, about 20 projections for 6 detectable features seem to be sufficient for a target estimation accuracy of 0.2 cm, even for relatively large feature detection errors with standard deviation of 0.5 cm and spatial displacements of the features with standard deviation of 0.5 cm. Conclusions: The authors have introduced a general MAP-based patient setup algorithm accounting for different sources of uncertainties, which are utilized as the prior knowledge in a transparent way. This new framework can be further utilized for different clinical sites, as well as theoretical developments in the field of patient positioning for radiotherapy.« less

Optimization of breast mass classification using sequential forward floating selection (SFFS) and a support vector machine (SVM) model

PubMed Central

Tan, Maxine; Pu, Jiantao; Zheng, Bin

2014-01-01

Purpose: Improving radiologists’ performance in classification between malignant and benign breast lesions is important to increase cancer detection sensitivity and reduce false-positive recalls. For this purpose, developing computer-aided diagnosis (CAD) schemes has been attracting research interest in recent years. In this study, we investigated a new feature selection method for the task of breast mass classification. Methods: We initially computed 181 image features based on mass shape, spiculation, contrast, presence of fat or calcifications, texture, isodensity, and other morphological features. From this large image feature pool, we used a sequential forward floating selection (SFFS)-based feature selection method to select relevant features, and analyzed their performance using a support vector machine (SVM) model trained for the classification task. On a database of 600 benign and 600 malignant mass regions of interest (ROIs), we performed the study using a ten-fold cross-validation method. Feature selection and optimization of the SVM parameters were conducted on the training subsets only. Results: The area under the receiver operating characteristic curve (AUC) = 0.805±0.012 was obtained for the classification task. The results also showed that the most frequently-selected features by the SFFS-based algorithm in 10-fold iterations were those related to mass shape, isodensity and presence of fat, which are consistent with the image features frequently used by radiologists in the clinical environment for mass classification. The study also indicated that accurately computing mass spiculation features from the projection mammograms was difficult, and failed to perform well for the mass classification task due to tissue overlap within the benign mass regions. Conclusions: In conclusion, this comprehensive feature analysis study provided new and valuable information for optimizing computerized mass classification schemes that may have potential to be useful as a “second reader” in future clinical practice. PMID:24664267

Wells syndrome and its relationship to Churg-Strauss syndrome.

PubMed

Ratzinger, Gudrun; Zankl, Julia; Zelger, Bernhard

2013-08-01

  Wells syndrome has been described as an inflammatory disorder based on typical clinical appearance combined with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Churg-Strauss syndrome, on the other hand, is primarily a diffuse, necrotizing vasculitis but is also typically displaying eosinophils and flame figures. Despite several parallels, the present understanding of these two diseases excludes any pathogenetic relationship.   We describe the clinical course and histopathological appearance of three patients who had initially been diagnosed with Wells syndrome that developed into Churg-Strauss syndrome during the course of their disease.   The clinical presentation of all three patients led to the diagnosis of Wells syndrome by independent specialists. Histopathology showed an eosinophilic infiltrate and flame figures next to features of leukocytoclastic vasculitis. Detailed examination revealed asthma bronchiale and additional symptoms indicating Churg-Strauss syndrome. The initial diagnosis of Wells syndrome had to be revised to Churg-Strauss syndrome.   We conclude that Wells syndrome could be the starting point of a pathogenetic process that might reach its maximum in Churg-Strauss syndrome. As a clinical consequence, patients with Wells syndrome should be evaluated and followed for Churg-Strauss syndrome. © 2013 The International Society of Dermatology.

Evaluation of clinical, laboratory, imaging findings and outcome in 99 dogs with leptospirosis.

PubMed

Knöpfler, S; Mayer-Scholl, A; Luge, E; Klopfleisch, R; Gruber, A D; Nöckler, K; Kohn, B

2017-10-01

To report clinical, laboratory and diagnostic imaging features and prognostic factors in dogs with leptospirosis from North-East Germany. Medical records of dogs diagnosed with leptospirosis from 2006 to 2013 were evaluated retrospectively. The study included 99 dogs. At initial presentation, the most common clinical signs were lethargy (96%), anorexia (88%), vomiting (85%), painful abdomen (39%), diarrhoea (38%), oliguria (27%) and tachypnoea (26%). Abnormal laboratory findings included anaemia (63%), thrombocytopenia (63%), leucocytosis (57%), increase of plasma urea (84%) and creatinine concentrations (81%), increased liver enzyme activities (80%), hyperbilirubinaemia (69%), hyperphosphataemia (67%), hyponatraemia (64%), hypoalbuminaemia (55%) and hypokalaemia (29%). Radiological pulmonary changes were detected in 57% of the dogs initially or during the course of disease. Severe dyspnoea, oliguria, azotaemia, hyperbilirubinaemia and severe radiological pulmonary changes were more often found in dogs that did not survive. There was renal, hepatic and pulmonary involvement in 95, 92 and 58% of the dogs, respectively, and multi-organ lesions in 98 dogs (98%); 32 dogs died or were euthanased. Several clinical and laboratory abnormalities were associated with a negative outcome; severe lung involvement was specifically associated with high mortality. © 2017 British Small Animal Veterinary Association.

Phenotype, biochemical features, genotype and treatment outcome of pyridoxine-dependent epilepsy.

PubMed

Al Teneiji, Amal; Bruun, Theodora U J; Cordeiro, Dawn; Patel, Jaina; Inbar-Feigenberg, Michal; Weiss, Shelly; Struys, Eduard; Mercimek-Mahmutoglu, Saadet

2017-04-01

We report treatment outcome of eleven patients with pyridoxine-dependent epilepsy caused by pathogenic variants in ALDH7A1 (PDE-ALDH7A1). We developed a clinical severity score to compare phenotype with biochemical features, genotype and delays in the initiation of pyridoxine. Clinical severity score included 1) global developmental delay/ intellectual disability; 2) age of seizure onset prior to pyridoxine; 3) current seizures on treatment. Phenotype scored 1-3 = mild; 4-6 = moderate; and 7-9 = severe. Five patients had mild, four patients had moderate, and two patients had severe phenotype. Phenotype ranged from mild to severe in eight patients (no lysine-restricted diet in the infantile period) with more than 10-fold elevated urine or plasma α-AASA levels. Phenotype ranged from mild to moderate in patients with homozygous truncating variants and from moderate to severe in patients with homozygous missense variants. There was no correlation between severity of the phenotype and the degree of α-AASA elevation in urine or genotype. All patients were on pyridoxine, nine patients were on arginine and five patients were on the lysine-restricted diet. 73% of the patients became seizure free on pyridoxine. 25% of the patients had a mild phenotype on pyridoxine monotherapy. Whereas, 100% of the patients, on the lysine-restricted diet initiated within their first 7 months of life, had a mild phenotype. Early initiation of lysine-restricted diet and/or arginine therapy likely improved neurodevelopmental outcome in young patients with PDE-ALDH7A1.

POLD1 Germline Mutations in Patients Initially Diagnosed with Werner Syndrome

PubMed Central

Lessel, Davor; Hisama, Fuki M.; Szakszon, Katalin; Saha, Bidisha; Sanjuanelo, Alexander Barrios; Salbert, Bonnie A.; Steele, Pamela D.; Baldwin, Jennifer; Brown, W. Ted; Piussan, Charles; Plauchu, Henri; Szilvássy, Judit; Horkay, Edit; Hoögel, Josef; Martin, George M.; Herr, Alan J.; Oshima, Junko; Kubisch, Christian

2015-01-01

Segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ. A prototypic example is the Werner syndrome (WS), caused by biallelic germline mutations in the Werner helicase gene (WRN). While heterozygous lamin A/C (LMNA) mutations are found in a few nonclassical cases of WS, another 10%–15% of patients initially diagnosed with WS do not have mutations in WRN or LMNA. Germline POLD1 mutations were recently reported in five patients with another segmental progeroid disorder: mandibular hypoplasia, deafness, progeroid features syndrome. Here, we describe eight additional patients with heterozygous POLD1 mutations, thereby substantially expanding the characterization of this new example of segmental progeroid disorders. First, we identified POLD1 mutations in patients initially diagnosed with WS. Second, we describe POLD1 mutation carriers without clinically relevant hearing impairment or mandibular underdevelopment, both previously thought to represent obligate diagnostic features. These patients also exhibit a lower incidence of metabolic abnormalities and joint contractures. Third, we document postnatal short stature and premature greying/loss of hair in POLD1 mutation carriers. We conclude that POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome. PMID:26172944

Current situation of asthma-COPD overlap syndrome (ACOS) in Chinese patients older than 40 years with airflow limitation: rationale and design for a multicenter, cross-sectional trial (study protocol).

PubMed

Kang, Jian; Yao, Wanzhen; Cai, Baiqiang; Chen, Ping; Ling, Xia; Shang, Hongyan

2016-12-01

Asthma and chronic obstructive pulmonary disease (COPD) are the frequently occurring chronic airway diseases, and the overlapping syndrome observed in the majority of patients has been recently defined as asthma-COPD overlap syndrome (ACOS) by the Global Initiative for Chronic Obstructive Lung (GOLD, 2014) and Global initiative for Asthma (GINA, 2015). The proportion, features, and clinical practice of ACOS still remain elusive in China. We are conducting this multicenter, cross-sectional, observational study (NCT02600221) to investigate the distributions of chronic obstructive diseases in patients >40 years of age with chronic airflow limitation in China along with determination of the main clinical practice and features of these diseases. The study will also explore the factors that may influence the exacerbations and severity of ACOS in Chinese patients (>40 years of age). A total of 2,000 patients (age, ≥40 years; either sex) who are clinically diagnosed as having asthma, COPD/chronic bronchitis/emphysema, or ACOS for at least 12 months with airflow limitation [post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV 1 /FVC): <0.7] will be enrolled from approximately 20 sites in China between December 2015 and December 2016. The proportion of ACOS among patients older than 40 years based on GINA 2015 and GOLD 2014 definitions is the primary variable. Following were the secondary variables: the proportions of COPD and asthma among the patients, distributions of the severity of airflow limitation, distribution of groups according to GOLD 2011 group definition (A, B, C, D), and the distribution of medication by drug class in patients with ACOS, asthma, and COPD. Acute exacerbation history, hospitalization, and severity of ACOS as evaluated using COPD Assessment Test, Asthma Control Questionnaire-5, and Modified British Medical Research Council in patients with ACOS were also assessed. This will be the first study to disseminate scientific knowledge on the current situation, main clinical practice, and features of ACOS, asthma, and COPD conditions in Chinese patients. The insights will be helpful in designing optimal management strategies for ACOS and redefining the healthcare development programs.

ON BECOMING ABLE TO PLAY: INDIVIDUAL CHILD PSYCHOANALYTIC PSYCHODRAMA AND THE DEVELOPMENT OF SYMBOLIZATION.

PubMed

Quagelli, Luca; Solano, Paola

2017-10-01

In this paper, the authors analyze the relevance and transformative potential of individual psychoanalytic psychodrama in the treatment of children with severe impairments in symbolization. Central features of this modality, including promoting the representation of early traumatic experiences, are presented and discussed. Specific features include double-envelope containment of the co-therapists' group and play leader, consequent diffraction of the transference-determining portrayal, gradual integration, and initial figuration of coexisting split-off fragments. Drawing on in-depth clinical material, the authors show how psychodrama tempers the potentially traumatic effects of the encounter with the object, allowing these patients to access the transitional area of play. © 2017 The Psychoanalytic Quarterly, Inc.

Clinical and biological features of multiple myeloma involving the gastrointestinal system.

PubMed

Talamo, Giampaolo; Cavallo, Federica; Zangari, Maurizio; Barlogie, Bart; Lee, Choon-Kee; Pineda-Roman, Mauricio; Kiwan, Elias; Krishna, Somashekar; Tricot, Guido

2006-07-01

We report 24 cases of multiple myeloma (MM) with involvement of the gastrointestinal (GI) system. We found a strong association with high A lactate dehydrogenase levels, plasmablastic morphology, and A unfavorable karyotype. GI involvement at the time of initial diagnosis was much rarer than later in the course of the disease. The A median survival after diagnosis of GI involvement was 7 months. Among 13 patients treated with stem cell transplantation, the response rate was 92%, and median progression-free survival was 4 months. We conclude that MM involving the GI system is associated with adverse biological features and with short-lasting remissions, even after A high-dose chemotherapy.

[Leigh syndrome and leukodystrophy due to partial succinate dehydrogenase deficiency: regression with riboflavin].

PubMed

Pinard, J M; Marsac, C; Barkaoui, E; Desguerre, I; Birch-Machin, M; Reinert, P; Ponsot, G

1999-04-01

Succinate dehydrogenase (SDH) deficiency is rare. Clinical manifestations can appear in infancy with a marked impairment of psychomotor development with pyramidal signs and extrapyramidal rigidity. A 10-month-old boy developed severe neurological features, evoking a Leigh syndrome; magnetic resonance imaging showed features of leukodystrophy. A deficiency in the complex II respiratory chain (succinate dehydrogenase [SDH]) was shown. The course was remarkable by the regression of neurological impairment under treatment by riboflavin. The delay of psychomotor development, mainly involving language, was moderate at the age of 5 years. The relatively good prognosis of this patient, despite severe initial neurological impairment, may be due to the partial enzyme deficiency and/or riboflavin administration.

Clinical predictors and outcome of metabolic acidosis in under-five children admitted to an urban hospital in Bangladesh with diarrhea and pneumonia.

PubMed

Chisti, Mohammod J; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, A S G; Bardhan, Pradip K; Dey, Sanjoy Kumer; Huq, Sayeeda; Das, Sumon Kumar; Salam, Mohammed A

2012-01-01

Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the diagnostic clinical features of radiological pneumonia which underscores the importance of early initiation of appropriate antibiotics to combat morbidity and deaths in such population.

Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.

PubMed

Castagna, Maria Grazia; Maino, Fabio; Cipri, Claudia; Belardini, Valentina; Theodoropoulou, Alexandra; Cevenini, Gabriele; Pacini, Furio

2011-09-01

After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.

Glioblastoma as differential diagnosis of autoimmune encephalitis.

PubMed

Vogrig, Alberto; Joubert, Bastien; Ducray, Francois; Thomas, Laure; Izquierdo, Cristina; Decaestecker, Kévin; Martinaud, Olivier; Gerardin, Emmanuel; Grand, Sylvie; Honnorat, Jérome

2018-03-01

To identify the clinical and radiological features that should raise suspicion for the autoimmune encephalitis (AE)-like presentation of glioblastoma. This is an observational, retrospective case series of patients referred to the French National Reference Center on Paraneoplastic Neurological Diseases for suspected AE (possible, probable or definite, using the 2016 criteria) who later received a final diagnosis of glioblastoma according to 2016 WHO criteria. An extensive literature search was also conducted for similar existing cases. Between 2014 and 2016, 306 patients were referred to our center for suspected AE. Six of these patients (2%) later developed pathologically confirmed glioblastoma. Thirteen patients (9 male) were included for analysis (6 from the present series and 7 from the literature); median age was 63. Initially, a diagnosis of AE was clinically suspected based on: working memory deficits (77%), seizures (62%) (including status epilepticus in 23%), and psychiatric symptoms (46%). Initial brain MRI was not in favor of a typical glioblastoma pattern and showed bilateral (54%) or unilateral selective limbic involvement. Five patients exhibited initial slight contrast enhancement. A clear inflammatory CSF was present in five patients and three from the literature showed autoantibody positivity (NMDAR, VGKC, GluRepsilon2). Median delay between suspicions of AE to GBM diagnosis was 3 months (range 1.5-24) and one patient from the literature was diagnosed post-mortem. An alternative diagnosis of glioblastoma should be considered in patients presenting initially as AE, especially in patients who do not fulfill the criteria for definite AE and in those with a poor clinical evolution despite initial improvement.

The evolution of the histology in pleomorphic xanthoastrocytomas in children: a study of 15 cases.

PubMed

Wu, Xiangru; Bandopadhayay, Pratiti; Ng, Jessica; Ashley, David; Chow, C W

2011-01-01

To review the clinicopathological spectrum and evolution of the histology of pleomorphic xanthoastrocytomas (PXAs) seen at a single children's hospital. PXAs were selected from the Royal Children's Hospital archives over 30 years. The clinical features and pathology were reviewed, specifically checking the histological variation between areas, and the changes between biopsies. Fifteen patients were identified. Ten had repeat biopsies. Eleven patients did not show histological features of anaplasia. Of these eleven, three did not show the characteristic histological features, which developed 3 and 11 years later in repeat biopsies in two. Seven showed uncommon potentially confusing histology. One died, one had stable disease and one had progressive disease. Three with incomplete initial surgery remained in complete remission following more surgery, radiotherapy and chemotherapy when the tumours progressed, up to 11 years later. Four patients did show anaplasia, with abrupt change from typical PXA in two, and years following initial biopsy in one. Of these four patients, three died, one with extensive metastasis. PXA should be considered in superficial cerebral tumours composed only of compact bundles of glial fibrillary acidic protein positive spindle cells with inconspicuous mitosis, even when the highly characteristic features of this tumour are not seen. The prominent variation in histology makes small biopsies difficult for diagnosis and assessing anaplasia. Patients with non-anaplastic tumours can often be salvaged by more treatment for tumour progression.

Assessing the impact of telestration on surgical telementoring: A randomized controlled trial.

PubMed

Budrionis, Andrius; Hasvold, Per; Hartvigsen, Gunnar; Bellika, Johan Gustav

2016-01-01

Using graphical annotations in surgical telementoring promises vast improvements in both clinical and educational outcomes. However, these assumptions do not consider the potential patient safety risks resulting from this feature. Major differences in regulations regarding the implementation of telestration encourage an assessment of the utility of this feature on the outcomes of telementoring sessions. Eight students participated in a randomized controlled trial, comparing verbal with annotation-supplemented telementoring via video conferencing. A remote mentor guided the participants through four localization exercises, identifying the features in a still laparoscopic surgery scene using a laparoscopic simulator. Clinical and educational outcomes were assessed; the time consumption and quality of mentoring were determined. The study revealed no significant difference in localizing the intervention between the studied methods, while educational outcomes favoured verbal mentoring. Telestration-supplemented guidance was considerably faster and resulted in fewer miscommunications between the mentor and mentee. The initial hypothesis of the major clinical and education benefits of telestration in telementoring was not supported. A potential 33% decrease in the duration of the mentored episodes is expected due to the ability to annotate live video content. However, the impact of time saving on the outcome of the procedure remains unclear. Regardless of the quantitative measures, most of the participants and the mentor agreed that graphical annotations provide advantages over verbal guidance. © The Author(s) 2015.

Predicting missing biomarker data in a longitudinal study of Alzheimer disease.

PubMed

Lo, Raymond Y; Jagust, William J

2012-05-01

To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD). The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005-2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI. CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ(42). Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD. The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.

Predicting missing biomarker data in a longitudinal study of Alzheimer disease

PubMed Central

Jagust, William J.; Aisen, Paul; Jack, Clifford R.; Toga, Arthur W.; Beckett, Laurel; Gamst, Anthony; Soares, Holly; C. Green, Robert; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Bandy, Dan; Chen, Kewei; Morris, John; Lee, Virginia M.-Y.; Korecka, Magdalena; Crawford, Karen; Neu, Scott; Harvey, Danielle; Kornak, John; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Buckholtz, Neil; Kaye, Jeffrey; Dolen, Sara; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Tang, Cheuk; Marzloff, George; Toledo-Morrell, Leylade; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given, Curtis A.; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Brand, Connie; Richard, Jennifer; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Graff-Radford MBBCH, Neill R; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Benincasa, Amanda L.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Wu, Chuang-Kuo; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Scott; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Jacobson, Sandra; Killiany, Ronald; Norbash, Alexander; Nair, Anil; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Borrie, Michael; Lee, T-Y; Bartha, Dr Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Englert, Jessica; Williamson, Jeff D.; Sink, Kaycee M.; Watkins, Franklin; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo

2012-01-01

Objective: To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD). Methods: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI. Results: CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD. Conclusion: The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD. PMID:22491869

Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

PubMed Central

Duraisingham, Sai S.; Buckland, Matthew; Dempster, John; Lorenzo, Lorena; Grigoriadou, Sofia; Longhurst, Hilary J.

2014-01-01

Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment. PMID:24971644

How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?

PubMed

Naci, Huseyin; Ioannidis, John P A

2015-01-01

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.

Undifferentiated febrile illnesses in military personnel.

PubMed

Burns, Daniel S; Bailey, Mark S

2013-09-01

Undifferentiated febrile illnesses (UFIs) present with acute symptoms, objective fever and no specific organ focus on clinical assessment. The term is mostly used in developing and tropical countries where a wide range of infections may be responsible. Laboratory diagnosis often requires specialist microbiology investigations that are not widely available, and serology tests that only become positive during convalescence. Optimal clinical management requires a good travel history, awareness of local endemic diseases, an understanding of the features that may help distinguish different causes and appropriate use of empirical antibiotics. This review describes the most common examples of UFI in military personnel on overseas deployments, and provides a practical approach to their initial management.

Trichotillomania: a case report with clinical and dermatoscopic differential diagnosis with alopecia areata.

PubMed

Pinto, Ana Cecília Versiani Duarte; Andrade, Tatiana Cristina Pedro Cordeiro de; Brito, Fernanda Freitas de; Silva, Gardênia Viana da; Cavalcante, Maria Lopes Lamenha Lins; Martelli, Antonio Carlos Ceribelli

2017-01-01

Trichotillomania is a psychodermatologic disorder characterized by uncontrollable urge to pull one's own hair. Differential diagnoses include the most common forms of alopecia such as alopecia areata. It is usually associated with depression and obsessive-compulsive disorder. Trichotillomania treatment standardization is a gap in the medical literature. Recent studies demonstrated the efficacy of N-acetylcysteine (a glutamate modulator) for the treatment of the disease. We report the clinical case of a 12-year-old female patient who received the initial diagnosis of alopecia areata, but presented with clinical and dermoscopic features of trichotillomania. She was treated with the combination of psychotropic drugs and N-acetylcysteine with good clinical response. Due to the chronic and recurring nature of trichotillomania, more studies need to be conducted for the establishment of a formal treatment algorithm.

Trichotillomania: a case report with clinical and dermatoscopic differential diagnosis with alopecia areata*

PubMed Central

Pinto, Ana Cecília Versiani Duarte; de Andrade, Tatiana Cristina Pedro Cordeiro; de Brito, Fernanda Freitas; da Silva, Gardênia Viana; Cavalcante, Maria Lopes Lamenha Lins; Martelli, Antonio Carlos Ceribelli

2017-01-01

Trichotillomania is a psychodermatologic disorder characterized by uncontrollable urge to pull one's own hair. Differential diagnoses include the most common forms of alopecia such as alopecia areata. It is usually associated with depression and obsessive-compulsive disorder. Trichotillomania treatment standardization is a gap in the medical literature. Recent studies demonstrated the efficacy of N-acetylcysteine (a glutamate modulator) for the treatment of the disease. We report the clinical case of a 12-year-old female patient who received the initial diagnosis of alopecia areata, but presented with clinical and dermoscopic features of trichotillomania. She was treated with the combination of psychotropic drugs and N-acetylcysteine with good clinical response. Due to the chronic and recurring nature of trichotillomania, more studies need to be conducted for the establishment of a formal treatment algorithm. PMID:28225970

Failure analysis of ceramic clinical cases using qualitative fractography.

PubMed

Scherrer, Susanne S; Quinn, Janet B; Quinn, George D; Kelly, J Robert

2006-01-01

To educate dental academic staff and clinicians on the application of descriptive (qualitative) fractography for analyses of clinical and laboratory failures of brittle materials such as glass and ceramic. The fracture surface topography of failed glass, glass fiber-reinforced composite, and ceramic restorations (Procera, Cerestore, In-Ceram, porcelain-fused-to-metal) was examined utilizing a scanning electron microscope. Replicas and original failed parts were scrutinized for classic fractographic features such as hackle, wake hackle, twist hackle, arrest lines, and mirrors. Failed surfaces of the veneering porcelain of ceramic and porcelain-fused-to-metal crowns exhibited hackle, wake hackle, twist hackle, arrest lines, and compression curl, which were produced by the interaction of the advancing crack with the microstructure of the material. Fracture surfaces of glass and glass fiber-reinforced composite showed additional features, such as velocity hackle and mirrors. The observed features were good indicators of the local direction of crack propagation and were used to trace the crack back to an initial starting area (the origin). Examples of failure analysis in this study are intended to guide the researcher in using qualitative (descriptive) fractography as a tool for understanding the failure process in brittle restorative materials and also for assessing possible design inadequacies.

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management

PubMed Central

Matsumoto, Alvin M.

2017-01-01

Abstract Context: Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic–pituitary–testicular axis pathology but have functional hypogonadism that is potentially reversible. Evidence Acquisition: Literature review from 1970 to October 2016. Evidence Synthesis: Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency–like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. Conclusions: There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy. PMID:28359097

Magnetic resonance imaging of injuries to the ankle joint: can it predict clinical outcome?

PubMed

Zanetti, M; De Simoni, C; Wetz, H H; Zollinger, H; Hodler, J

1997-02-01

To predict clinical outcome after ankle sprains on the basis of magnetic resonance (MR) findings. Twenty-nine consecutive patients (mean age 32.9 years, range 13-60 years) were examined clinically and with MR imaging both after trauma and following standardized conservative therapy. Various MR abnormalities were related to a clinical outcome score. There was a tendency for a better clinical outcome in partial, rather than complete, tears of the anterior talofibular ligament and when there was no fluid within the peroneal tendon sheath at the initial MR examination (P = 0.092 for either abnormality). A number of other MR features did not significantly influence clinical outcome, including the presence of a calcaneofibular ligament lesion and a bone bruise of the talar dome. Clinical outcome after ankle sprain cannot consistently be predicted by MR imaging, although MR imaging may be more accurate when the anterior talofibular ligament is only partially torn and there are no signs of injury to the peroneal tendon sheath.

Automatic classification of written descriptions by healthy adults: An overview of the application of natural language processing and machine learning techniques to clinical discourse analysis.

PubMed

Toledo, Cíntia Matsuda; Cunha, Andre; Scarton, Carolina; Aluísio, Sandra

2014-01-01

Discourse production is an important aspect in the evaluation of brain-injured individuals. We believe that studies comparing the performance of brain-injured subjects with that of healthy controls must use groups with compatible education. A pioneering application of machine learning methods using Brazilian Portuguese for clinical purposes is described, highlighting education as an important variable in the Brazilian scenario. The aims were to describe how to:(i) develop machine learning classifiers using features generated by natural language processing tools to distinguish descriptions produced by healthy individuals into classes based on their years of education; and(ii) automatically identify the features that best distinguish the groups. The approach proposed here extracts linguistic features automatically from the written descriptions with the aid of two Natural Language Processing tools: Coh-Metrix-Port and AIC. It also includes nine task-specific features (three new ones, two extracted manually, besides description time; type of scene described - simple or complex; presentation order - which type of picture was described first; and age). In this study, the descriptions by 144 of the subjects studied in Toledo 18 were used,which included 200 healthy Brazilians of both genders. A Support Vector Machine (SVM) with a radial basis function (RBF) kernel is the most recommended approach for the binary classification of our data, classifying three of the four initial classes. CfsSubsetEval (CFS) is a strong candidate to replace manual feature selection methods.

Microscopic Colitis – A Missed Diagnosis in Diarrhea-Predominant Irritable Bowel Syndrome

PubMed Central

STOICESCU, Adriana; BECHEANU, Gabriel; DUMBRAVA, Mona; GHEORGHE, Cristian; DICULESCU, Mircea

2012-01-01

ABSTRACT Background: Clinical presentation in microscopic colitis (MC) is similar in many cases to that of diarrhea-predominent irritable bowel syndrome (IBS-D). The proper differential diagnosis requires total colonoscopy with multiple biopsies from normal-appearing mucosa and a detailed histopathological exam. Specific treatment may improve symptomatology. Aim: To evaluate the prevalence of MC in patients with an initial diagnosis of IBS-D, to analyse demographic and clinical features of MC patients and to assess the efficacy of specific treatment. Material and methods: Our retrospective study analyzed patients diagnosed with microscopic colitis in clinic during a three-year period. Diagnosis was established on histological exams of the samples obtained during colonoscopy in patients previously thought to have IBS-D. We evaluated clinical manifestations, time lapsed from their onset to definitive diagnosis, the association of MC with autoimmune diseases or with prior medication and the efficacy of treatment with budesonide or mesalazine. Results: From 247 patients considered to have IBS-D, 15 patients (6.07%) had actually MC (13 lymphocytic colitis and 2 collagenous colitis). MC was associated with nonsteroidal antiinflammatory drugs (3 patients), Lansoprazole (2 patients) and autoimmune diseases (6 patients). Watery, non-bloody diarrhea was present in all patients with MC. Other frequent complaints were nocturnal diarrhea (11 patients), abdominal pain (8 patients), abdominal bloating and flatulence (8 patients) and slight weight loss (6 patients). The diagnostic samples were obtained from the right colon in 6 cases and from rectosigmoid or transverse colon in 9 patients. Treatment was initial symptomatic in all patients, but there were 5 patients that required mesalazine and/or Budesonide, with favourable outcome. Conclusions: All the patients thought to have diarrhea-irritable bowel syndrome should be evaluated for microscopic colitis. Symptomatology is almost superimposable, but a few distinct features can be noticed. The proper and early diagnosis and the specific treatment may lead to significant clinical improvement in some difficult cases of the so-called "irritable bowel syndrome". PMID:23118812

Microscopic colitis - a missed diagnosis in diarrhea-predominant irritable bowel syndrome.

PubMed

Stoicescu, Adriana; Becheanu, Gabriel; Dumbrava, Mona; Gheorghe, Cristian; Diculescu, Mircea

2012-01-01

Clinical presentation in microscopic colitis (MC) is similar in many cases to that of diarrhea-predominent irritable bowel syndrome (IBS-D). The proper differential diagnosis requires total colonoscopy with multiple biopsies from normal-appearing mucosa and a detailed histopathological exam. Specific treatment may improve symptomatology. To evaluate the prevalence of MC in patients with an initial diagnosis of IBS-D, to analyse demographic and clinical features of MC patients and to assess the efficacy of specific treatment. Our retrospective study analyzed patients diagnosed with microscopic colitis in clinic during a three-year period. Diagnosis was established on histological exams of the samples obtained during colonoscopy in patients previously thought to have IBS-D. We evaluated clinical manifestations, time lapsed from their onset to definitive diagnosis, the association of MC with autoimmune diseases or with prior medication and the efficacy of treatment with budesonide or mesalazine. From 247 patients considered to have IBS-D, 15 patients (6.07%) had actually MC (13 lymphocytic colitis and 2 collagenous colitis). MC was associated with nonsteroidal antiinflammatory drugs (3 patients), Lansoprazole (2 patients) and autoimmune diseases (6 patients). Watery, non-bloody diarrhea was present in all patients with MC. Other frequent complaints were nocturnal diarrhea (11 patients), abdominal pain (8 patients), abdominal bloating and flatulence (8 patients) and slight weight loss (6 patients). The diagnostic samples were obtained from the right colon in 6 cases and from rectosigmoid or transverse colon in 9 patients. Treatment was initial symptomatic in all patients, but there were 5 patients that required mesalazine and/or Budesonide, with favourable outcome. All the patients thought to have diarrhea-irritable bowel syndrome should be evaluated for microscopic colitis. Symptomatology is almost superimposable, but a few distinct features can be noticed. The proper and early diagnosis and the specific treatment may lead to significant clinical improvement in some difficult cases of the so-called "irritable bowel syndrome".

Clinical presentation and treatment of septic arthritis in children.

PubMed

Moro-Lago, I; Talavera, G; Moraleda, L; González-Morán, G

The aim of this study is to determine the epidemiological features, clinical presentation, and treatment of children with septic arthritis. A retrospective review was conducted on a total of 141 children with septic arthritis treated in Hospital Universitario La Paz (Madrid) between the years 2000 to 2013. The patient data collected included, the joint affected, the clinical presentation, the laboratory results, the appearance, Gram stain result, and the joint fluid culture, as well as the imaging tests and the treatment. Most (94%) of the patients were less than 2 years-old. The most common location was the knee (52%), followed by the hip (21%). The septic arthritis was confirmed in 53%. No type of fever was initially observed in 49% of them, and 18% had an ESR (mm/h) or CRP (mg/l) less than 30 in the initial laboratory analysis. The joint fluid was purulent in 45% and turbid in 12%. The Gram stain showed bacteria in 4%. The fluid culture was positive in 17%. Staphylococcus aureus was the most common pathogen found, followed by Streptococcus agalactiae, Streptococcus pneumoniae, and Kingella kingae. Antibiotic treatment was intravenous administration for 7 days, followed by 21 days orally. Surgery was performed in 18% of cases. The diagnosis was only confirmed in 53% of the patients. Some of the confirmed septic arthritis did not present with the classical clinical/analytical signs, demonstrating that the traumatologist or paediatrician requires a high initial level of clinical suspicion of the disease. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-venous thromboembolism study--methodological implications for clinical trials.

PubMed

Raskob, G; Büller, H; Prins, M; Segers, A; Shi, M; Schwocho, L; van Kranen, R; Mercuri, M

2013-07-01

New oral anticoagulants may simplify long-term therapy by eliminating the need for laboratory monitoring. Edoxaban is an oral, direct inhibitor of factor Xa that is given in a fixed dose once daily. The Hokusai-VTE study is a randomized, double-blind trial to evaluate whether initial low molecular weight heparin (LMWH) followed by edoxaban (60 mg once daily) is non-inferior to LMWH followed by warfarin (International Normalized Ratio of 2.0-3.0) for the prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism (VTE). The primary efficacy outcome is symptomatic recurrent VTE during the 12-month study period. The principal safety outcome is clinically relevant bleeding (major or non-major) occurring during or within 3 days of stopping study treatment. A clinical events committee adjudicates all suspected outcome events. A unique study design feature is the flexible treatment duration of between 3 and 12 months to simulate usual clinical practice, and enabled by: (i) double-blinding to minimize bias that could occur if knowledge of the patient's treatment influenced the duration of therapy; and (ii) follow-up for 12 months of all patients and inclusion in the primary efficacy analysis, regardless of the duration of therapy received. A second innovative design feature is the strategy for achieving an appropriate time in therapeutic range in the warfarin group, with central tracking for each participating center and feedback to the investigators. The standard methods combined with innovative design features should achieve study results that are both scientifically valid and relevant to clinical practice. © 2013 International Society on Thrombosis and Haemostasis.

Autoimmunity-Associated PTPN22 Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients.

PubMed

Heneberg, Petr; Kocková, Lucie; Čecháková, Marie; Daňková, Pavlína; Černá, Marie

2018-06-12

A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22. We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA. We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.-1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes). The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood. © 2018 S. Karger AG, Basel.

Clinical, computed tomographic, magnetic resonance imaging, and histologic findings associated with myxomatous neoplasia of the temporomandibular joint in two dogs.

PubMed

Parslow, Arana; Taylor, David P; Simpson, David J

2016-12-01

CASE DESCRIPTION A 15-year-old neutered female mixed-breed dog (dog 1) and an 11-year-old neutered female Labrador Retriever (dog 2) were examined because of unilateral exophthalmus, third eyelid protrusion, and periorbital swelling that failed to respond to antimicrobial treatment. CLINICAL FINDINGS Both dogs underwent ultrasonographic, CT, and MRI examination of the head. In both dogs, advanced imaging revealed a poorly defined, peripherally contrast-enhancing, mucous-filled cystic mass that radiated from the temporomandibular joint and infiltrated the periorbital tissues and retrobulbar space. Both dogs underwent surgical biopsy of the periorbital mass. A viscous, straw-colored fluid was aspirated from the retrobulbar region in both dogs. The initial histologic diagnosis for dog 1 was zygomatic sialadenitis and sialocele. However, the clinical signs recurred, and histologic examination of specimens obtained during a second surgical biopsy resulted in a diagnosis of myxoma. The histologic diagnosis was myxosarcoma for dog 2. TREATMENT AND OUTCOME In both dogs, clinical signs recurred within 2 weeks after surgery and persisted for the duration of their lives. Dog 1 received no further treatment after the second surgery and was euthanized 34 months after initial examination because of multicentric lymphoma. Dog 2 was treated with various chemotherapy agents and was euthanized 11 months after initial examination because of a dramatic increase in periocular swelling and respiratory stertor. CLINICAL RELEVANCE Temporomandibular myxomatous neoplasia can be confused with zygomatic sialocele on the basis of clinical signs but has characteristic MRI features. Representative biopsy specimens should be obtained from areas close to the temporomandibular joint to avoid misdiagnosis.

Previously undiagnosed hereditary spherocytosis in a patient with jaundice and pyelonephritis: a case report.

PubMed

Tateno, Yuki; Suzuki, Ryoji; Kitamura, Yukihiro

2016-12-01

Hereditary spherocytosis is autosomal dominant inherited extravascular hemolytic disorder and is the commonest cause of inherited hemolysis in northern Europe and the United States. The classical clinical features of hereditary spherocytosis are anemia, jaundice, and splenomegaly. However, all of these classical features are not always revealed in the case of mild hemolysis or when hemolysis is well compensated. Patients with hereditary spherocytosis may remain undiagnosed for years if their hemolysis is mild. A 42-year-old Asian woman presented to our clinic with a sudden onset of high fever with shaking chills and jaundice, suggesting septicemia; however, following detailed investigation, the patient was diagnosed with pyelonephritis and accelerated hemolysis of hereditary spherocytosis due to infection. It is important to note that transient anemia or jaundice can sometimes be the only initial presenting symptoms in cases of undiagnosed latent hereditary spherocytosis. This case also highlights the fact that physicians should consider concomitant hemolytic disease in patients in whom jaundice and infections that rarely cause jaundice coexist.

Optic Nerve Lymphoma. Report of Two Cases and Review of the Literature

PubMed Central

Kim, Jennifer L.; Mendoza, Pia; Rashid, Alia; Hayek, Brent; Grossniklaus, Hans E.

2014-01-01

Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with CNS or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging, and cerebrospinal fluid evaluation as part of the initial work-up, then judicious use of optic nerve biopsy, depending on the clinical situation. PMID:25595061

Single- and double-row repair for rotator cuff tears - biology and mechanics.

PubMed

Papalia, Rocco; Franceschi, Francesco; Vasta, Sebastiano; Zampogna, Biagio; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

We critically review the existing studies comparing the features of single- and double-row repair, and discuss suggestions about the surgical indications for the two repair techniques. All currently available studies comparing the biomechanical, clinical and the biological features of single and double row. Biomechanically, the double-row repair has greater performances in terms of higher initial fixation strength, greater footprint coverage, improved contact area and pressure, decreased gap formation, and higher load to failure. Results of clinical studies demonstrate no significantly better outcomes for double-row compared to single-row repair. Better results are achieved by double-row repair for larger lesions (tear size 2.5-3.5 cm). Considering the lack of statistically significant differences between the two techniques and that the double row is a high cost and a high surgical skill-dependent technique, we suggest using the double-row technique only in strictly selected patients. Copyright © 2012 S. Karger AG, Basel.

High altitude pulmonary edema-clinical features, pathophysiology, prevention and treatment

PubMed Central

Paralikar, Swapnil J.

2012-01-01

High altitude pulmonary edema (HAPE) is a noncardiogenic pulmonary edema which typically occurs in lowlanders who ascend rapidly to altitudes greater than 2500-3000 m. Early symptoms of HAPE include a nonproductive cough, dyspnoea on exertion and reduced exercise performance. Later, dyspnoea occurs at rest. Clinical features are cyanosis, tachycardia, tachypnoea and elevated body temperature generally not exceeding 38.5°C. Rales are discrete initially and located over the middle lung fields. HAPE mainly occurs due to exaggerated hypoxic pulmonary vasoconstriction and elevated pulmonary artery pressure. It has been observed that HAPE is a high permeability type of edema occurring also due to leaks in the capillary wall (‘stress failure’). Slow descent is the most effective method for prevention; in addition, graded ascent and time for acclimatization, low sleeping altitudes, avoidance of alcohol and sleeping pills, and avoidance of exercise are the key to preventing HAPE. Treatment of HAPE consists of immediate improvement of oxygenation either by supplemental oxygen, hyperbaric treatment, or by rapid descent. PMID:23580834

Development of outcome measures for large-vessel vasculitis for use in clinical trials: opportunities, challenges, and research agenda.

PubMed

Direskeneli, Haner; Aydin, Sibel Z; Kermani, Tanaz A; Matteson, Eric L; Boers, Maarten; Herlyn, Karen; Luqmani, Raashid A; Neogi, Tuhina; Seo, Philip; Suppiah, Ravi; Tomasson, Gunnar; Merkel, Peter A

2011-07-01

Giant cell (GCA) and Takayasu's arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development.

Development of Outcome Measures for Large-vessel Vasculitis for Use in Clinical Trials: Opportunities, Challenges, and Research Agenda

PubMed Central

DIRESKENELI, HANER; AYDIN, SIBEL Z.; KERMANI, TANAZ A.; MATTESON, ERIC L.; BOERS, MAARTEN; HERLYN, KAREN; LUQMANI, RAASHID A.; NEOGI, TUHINA; SEO, PHILIP; SUPPIAH, RAVI; TOMASSON, GUNNAR; MERKEL, PETER A.

2013-01-01

Giant cell (GCA) and Takayasu’s arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development. PMID:21724719

Clinical characteristics of central diabetes insipidus in Taiwanese children.

PubMed

Liu, Shih-Yao; Tung, Yi-Ching; Lee, Cheng-Ting; Liu, Hon-Man; Peng, Shinn-Forng; Wu, Mu-Zon; Kuo, Meng-Fai; Tsai, Wen-Yu

2013-10-01

Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions. Copyright © 2013. Published by Elsevier B.V.

Microvascular changes during acne lesion initiation and scarring is revealed in vivo using optical microangiography

NASA Astrophysics Data System (ADS)

Baran, Utku; Li, Yuandong; Choi, Woo J.; Wang, Ruikang K.

2015-02-01

Acne is a common skin disease in society and often leads to scarring. In this paper, we demonstrate the capabilities of swept-source optical coherence tomography (SS-OCT) in detecting specific features of acne lesion initiation and scarring on human facial skin in vivo over 30 days. Optical microangiography (OMAG) technique made it possible to image 3D tissue microvasculature changes up to 1 mm depth in vivo without the need of exogenous contrast agents in ~10 seconds. The presented results show promise to facilitate clinical trials of treatment and prognosis of acne vulgaris by detecting cutaneous microvasculature and structural changes within human skin in vivo.

Prolonged fever in peritoneal tuberculosis: A case report

NASA Astrophysics Data System (ADS)

Zein, U.; Irwandi, S.; Habib, H.; Lim, H.; Pasha, M.; Janis, I.; Saragih, R. H.; Ginting, Y.; Effendy-Y S, R.

2018-03-01

Peritoneal tuberculosis may lead to delayed diagnosis because of the nonspecific features such as fever, abdominal distension, abdominal tenderness, ascites, and weight loss. Here, wereported a case of prolonged fever and abdominal pain which was due to peritoneal tuberculosis. Initial examinations including acomplete blood test and serologic tests did not lead to the diagnosis. A final diagnosis was made by abdominal CT-scan and laparoscopy combined with histopathological studies. Antituberculous medications provided a good clinical response in this patient.

CRNDE: An important oncogenic long non-coding RNA in human cancers.

PubMed

Zhang, Jiaming; Yin, Minuo; Peng, Gang; Zhao, Yingchao

2018-06-01

Aberrant overexpression of long non-coding RNA CRNDE (Colorectal Neoplasia Differentially Expressed) is confirmed in various human cancers, which is correlated with advanced clinicopathological features and poor prognosis. CRNDE promotes cancer cell proliferation, migration and invasion, and suppresses apoptosis in complicated mechanisms, which result in the initialization and development of human cancers. In this review, we provide an overview of the oncogenic role and potential clinical applications of CRNDE. © 2018 John Wiley & Sons Ltd.

IDH1 R132H mutation in a pilocytic astrocytoma: a case report.

PubMed

Behling, Felix; Steinhilber, Julia; Tatagiba, Marcos; Bisdas, Sotirios; Schittenhelm, Jens

2015-01-01

We present the case of a 72-year old female with a right cerebellar pilocytic astrocytoma WHO grade I with an Isocitrate dehydrogenase 1 (IDH1) R132H mutation. The patient is recurrence-free 6 years after the initial diagnosis. Only one single case with strikingly similar clinicopathological features has been reported before. Otherwise, IDH1/2 mutations are not seen in pilocytic astrocytomas. The clinical implications of these findings are discussed.

Review of influential articles in surgical education: 2002-2012.

PubMed

Wohlauer, Max V; George, Brian; Lawrence, Peter F; Pugh, Carla M; Van Eaton, Erik G; Darosa, Debra

2013-06-01

Exploring the trends in surgical education research offers insight into concerns, developments, and questions researchers are exploring that are relevant to teaching and learning in surgical specialties. We conducted a review of the surgical education literature published between 2002 and 2012. The purpose was 2-fold: to provide an overview of the most frequently cited articles in the field of surgical education during the last decade and to describe the study designs and themes featured in these articles. Articles were identified through Web of Science by using "surgical education" and "English language" as search terms. Using a feature in Web of Science, we tracked the number of citations of any publication. Of the 800 articles produced by the initial search, we initially selected 23 articles with 45 or more citations, and ultimately chose the 20 articles that were most frequently cited for our analysis. Analysis of the most frequently cited articles published in US journals between the years 2002-2012 identified 7 research themes and presented them in order of frequency with which they appear: use of simulation, issues in student/resident assessment, specialty choice, patient safety, team training, clinical competence assessment, and teaching the clinical sciences, with surgical simulation being the central theme. Researchers primarily used descriptive methods. Popular themes in surgical education research illuminate the information needs of surgical educators as well as topics of high interest to the surgical community.

Is PIGD a legitimate motor subtype in Parkinson disease?

PubMed

Kotagal, Vikas

2016-06-01

Parkinson disease is a chronic progressive syndrome with a broad array of clinical features. Different investigators have suggested the heterogeneous motor manifestations of early Parkinson disease can be conceptualized through a taxonomy of clinical subtypes including tremor-predominant and postural instability and gait difficulty-predominant subtypes. Although it is theoretically valuable to distinguish subtypes of Parkinson disease, the reality is that few patients fit these discrete categories well and many transition from exhibiting elements of one subtype to elements of another. In the time since the initial description of the postural instability and gait difficulty-predominant subtype, Parkinson disease clinical research has blossomed in many ways - including an increased emphasis on the role of medical comorbidities and extranigral pathologies in Parkinson disease as markers of prognostic significance. By conceptualizing the pathogenesis of an expansive disease process in the limited terms of categorical motor subtypes, we run the risk of overlooking or misclassifying clinically significant pathogenic risk factors that lead to the development of motor milestones such as falls and related axial motor disability. Given its critical influence on quality of life and overall prognosis, we are in need of a model of postural instability and gait difficulty-predominant features in Parkinson disease that emphasizes the overlooked pathological influence of aging and medical comorbidities on the development of axial motor burden and postural instability and gait difficulty-predominant features. This Point of View proposes thinking of postural instability and gait difficulties in Parkinson disease not as a discrete subtype, but rather as multidimensional continuum influenced by several overlapping age-related pathologies.

A Review of Smoking Research In Malaysia.

PubMed

Wee, L H; Chan, C M H; Yogarabindranath, S N

2016-06-01

Two hundred and seventy one original published materials related to tobacco use were found in a search through a database dedicated to indexing all original data relevant to Medicine and Health in Malaysia from 1996 - 2015. A total of 147 papers were selected and reviewed on the basis of their relevance and implications for future research. Findings were summarised, categorised and presented according to epidemiology, behaviour, clinical features and management of smoking. Most studies are cross-sectional with small sample sizes. Studies on smoking initiation and prevalence showed mixed findings with many small scale studies within the sub-groups. The majority of the studies were related to factors that contribute to initiation in adolescents. Nonetheless, there are limited studies on intervention strategies to curb smoking among this group. There is a lack of clinical studies to analyse tobacco use and major health problems in Malaysia. In addition, studies on the best treatment modalities on the use of pharmacotherapy and behavioural counselling have also remained unexplored. Reasons why smokers do not seek clinic help to quit smoking need further exploration. A finding on the extent of effort carried out by healthcare providers in assisting smokers to make quit attempts is not known. Studies on economic and government initiatives on policies and tobacco use focus mainly on the effects of cigarette bans, increased cigarettes taxes and the influence of the tobacco industry. Recommendations are given for the government to increase efforts in implementing smoke-free legislation, early and tailored interventions. Clinical studies in this area are lacking, as are opportunities to research on ways to reduce smoking initiation age and the most effective quit smoking strategies.

Corticobasal degeneration initially developing motor versus non-motor symptoms: a comparative clinicopathological study.

PubMed

Ikeda, Chikako; Yokota, Osamu; Nagao, Shigeto; Ishizu, Hideki; Morisada, Yumi; Terada, Seishi; Nakashima, Yoshihiko; Akiyama, Haruhiko; Uchitomi, Yosuke

2014-09-01

Clinical presentations of pathologically confirmed corticobasal degeneration (CBD) vary, and the heterogeneity makes its clinical diagnosis difficult, especially when a patient lacks any motor disturbance in the early stage. We compared clinical and pathological features of four pathologically confirmed CBD cases that initially developed non-motor symptoms, including behavioural and psychiatric symptoms but without motor disturbance (CBD-NM), and five CBD cases that initially developed parkinsonism and/or falls (CBD-M). The age range at death for the CBD-NM and CBD-M subjects (58-85 years vs 45-67 years) and the range of disease duration (2-18 years vs 2-6 years) did not significantly differ between the groups. Prominent symptoms in the early stage of CBD-NM cases included self-centred behaviours such as frontotemporal dementia (n = 1), apathy with and without auditory hallucination (n = 2), and aggressive behaviours with delusion and visual hallucination (n = 1). Among the four CBD-NM cases, only one developed asymmetric motor disturbance, and two could walk without support throughout the course. Final clinical diagnoses of the CBD-NM cases were frontotemporal dementia (n = 2), senile psychosis with delirium (n = 1), and schizophrenia (n = 1). Neuronal loss was significantly less severe in the subthalamic nucleus and substantia nigra in the CBD-NM cases than in the CBD-M cases. The severity of tau pathology in all regions examined was comparable in the two groups. CBD cases that initially develop psychiatric and behavioural changes without motor symptoms may have less severe degenerative changes in the subthalamic nucleus and substantia nigra, and some CBD cases can lack motor disturbance not only in the early stage but also in the last stage of the course. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

Depression and anxiety in a case series of amyotrophic lateral sclerosis: frequency and association with clinical features

PubMed Central

Prado, Laura de Godoy Rousseff; Bicalho, Isabella Carolina Santos; Vidigal-Lopes, Mauro; Prado, Vitor de Godoy Rousseff; Gomez, Rodrigo Santiago; de Souza, Leonardo Cruz; Teixeira, Antônio Lúcio

2017-01-01

ABSTRACT Objective To investigate the frequency of anxiety and depression and their association with clinical features of amyotrophic lateral sclerosis. Methods This is a cross-sectional and descriptive study including a consecutive series of patients with sporadic amyotrophic lateral sclerosis according to Awaji’s criteria. Patients underwent clinical and psychiatric assessment (anxiety and depression symptoms). Results We included 76 patients. The men/women ratio was 1.6:1. Participants’ mean age at disease onset was 55 years (SD±12.1). Sixty-six patients (86.8%) were able to complete psychiatric evaluation. Clinically significant anxiety was found in 23 patients (34.8%) while clinically significant depression was found in 24 patients (36.4%). When we compared patients with and without depression a significant difference was seen only in the frequency of anxiety symptoms (p<0.001). We did further analysis comparing subgroups of patients classified according to the presence or not of anxiety and or depression, without any significant difference regarding sex, age at onset, initial form, disease duration or functional measures. A positive correlation between anxiety and depressive symptoms was found (p<0.001). Conclusion Anxiety and depressive symptoms were highly correlated and frequent in patients with amyotrophic lateral sclerosis. In addition, anxiety and depression were not associated with disease duration and presentation, sex, age at onset, and functional score. PMID:28444090

Aspects of the Patient-centered Medical Home currently in place: initial findings from preparing the personal physician for practice.

PubMed

Carney, Patricia A; Eiff, M Patrice; Saultz, John W; Douglass, Alan B; Tillotson, Carrie J; Crane, Steven D; Jones, Samuel M; Green, Larry A

2009-10-01

The Patient-centered Medical Home (PCMH) is a central concept in the evolving debate about American health care reform. We studied family medicine residency training programs' continuity clinics to assess baseline status of implementing PCMH components and to compare implementation status between community-based and university training programs. We conducted a survey 24 continuity clinics in 14 residency programs that are part of the Preparing the Personal Physicians for Practice (P(4)) program. We asked questions about aspects of P(4) that had been already implemented at the beginning of the P(4) program. We defined high implementation as aspects that were present in >50% of clinics and low implementation as those present in <50% of clinics. We compared features at university-based and community-based clinics. High areas of implementation were having an electronic health record (EHR), fully secured remote access, electronic patient notes/scheduling/billing, chronic disease management registries, and open-access scheduling. Low areas of implementation included hospital EHR with computerized physician order entry, asynchronous communication with patients, ongoing population-based QA using EHR, use of preventive registries, and practice-based research using EHR. Few differences were noted between university- and community-based residency programs. Many features of the PCMH were already established at baseline in programs participating in P(4).

Achieving Accurate Automatic Sleep Staging on Manually Pre-processed EEG Data Through Synchronization Feature Extraction and Graph Metrics.

PubMed

Chriskos, Panteleimon; Frantzidis, Christos A; Gkivogkli, Polyxeni T; Bamidis, Panagiotis D; Kourtidou-Papadeli, Chrysoula

2018-01-01

Sleep staging, the process of assigning labels to epochs of sleep, depending on the stage of sleep they belong, is an arduous, time consuming and error prone process as the initial recordings are quite often polluted by noise from different sources. To properly analyze such data and extract clinical knowledge, noise components must be removed or alleviated. In this paper a pre-processing and subsequent sleep staging pipeline for the sleep analysis of electroencephalographic signals is described. Two novel methods of functional connectivity estimation (Synchronization Likelihood/SL and Relative Wavelet Entropy/RWE) are comparatively investigated for automatic sleep staging through manually pre-processed electroencephalographic recordings. A multi-step process that renders signals suitable for further analysis is initially described. Then, two methods that rely on extracting synchronization features from electroencephalographic recordings to achieve computerized sleep staging are proposed, based on bivariate features which provide a functional overview of the brain network, contrary to most proposed methods that rely on extracting univariate time and frequency features. Annotation of sleep epochs is achieved through the presented feature extraction methods by training classifiers, which are in turn able to accurately classify new epochs. Analysis of data from sleep experiments on a randomized, controlled bed-rest study, which was organized by the European Space Agency and was conducted in the "ENVIHAB" facility of the Institute of Aerospace Medicine at the German Aerospace Center (DLR) in Cologne, Germany attains high accuracy rates, over 90% based on ground truth that resulted from manual sleep staging by two experienced sleep experts. Therefore, it can be concluded that the above feature extraction methods are suitable for semi-automatic sleep staging.

Achieving Accurate Automatic Sleep Staging on Manually Pre-processed EEG Data Through Synchronization Feature Extraction and Graph Metrics

PubMed Central

Chriskos, Panteleimon; Frantzidis, Christos A.; Gkivogkli, Polyxeni T.; Bamidis, Panagiotis D.; Kourtidou-Papadeli, Chrysoula

2018-01-01

Sleep staging, the process of assigning labels to epochs of sleep, depending on the stage of sleep they belong, is an arduous, time consuming and error prone process as the initial recordings are quite often polluted by noise from different sources. To properly analyze such data and extract clinical knowledge, noise components must be removed or alleviated. In this paper a pre-processing and subsequent sleep staging pipeline for the sleep analysis of electroencephalographic signals is described. Two novel methods of functional connectivity estimation (Synchronization Likelihood/SL and Relative Wavelet Entropy/RWE) are comparatively investigated for automatic sleep staging through manually pre-processed electroencephalographic recordings. A multi-step process that renders signals suitable for further analysis is initially described. Then, two methods that rely on extracting synchronization features from electroencephalographic recordings to achieve computerized sleep staging are proposed, based on bivariate features which provide a functional overview of the brain network, contrary to most proposed methods that rely on extracting univariate time and frequency features. Annotation of sleep epochs is achieved through the presented feature extraction methods by training classifiers, which are in turn able to accurately classify new epochs. Analysis of data from sleep experiments on a randomized, controlled bed-rest study, which was organized by the European Space Agency and was conducted in the “ENVIHAB” facility of the Institute of Aerospace Medicine at the German Aerospace Center (DLR) in Cologne, Germany attains high accuracy rates, over 90% based on ground truth that resulted from manual sleep staging by two experienced sleep experts. Therefore, it can be concluded that the above feature extraction methods are suitable for semi-automatic sleep staging. PMID:29628883

Histological variability and the importance of clinicopathological correlation in cutaneous Rosai-Dorfman disease.

PubMed

Gameiro, Ana; Gouveia, Miguel; Cardoso, José Carlos; Tellechea, Oscar

2016-01-01

Rosai-Dorfman disease is a benign histiocytic proliferative disorder of unknown etiology. The disease mainly affects lymph node tissue, although it is rarely confined to the skin. Here, we describe a 53-year-old woman with purely cutaneous Rosai-Dorfman disease. The patient presented with a large pigmented plaque on her left leg, and sparse erythematous papules on her face and arms. A complete clinical response was achieved with thalidomide, followed by recurrence at the initial site one year later. The histological examination displayed the typical features of Rosai-Dorfman disease in the recent lesions but not in the older lesions. In the setting of no lymphadenopathy, the histopathological features of Rosai-Dorfman disease are commonly misinterpreted. Therefore, awareness of the histological aspects present at different stages, not always featuring the hallmark microscopic signs of Rosai-Dorfman disease, is particularly important for a correct diagnosis of this rare disorder.

Clinical features and outcomes of patients with hepatocellular carcinoma complicated with bile duct invasion.

PubMed

An, Jihyun; Lee, Kwang Sun; Kim, Kang Mo; Park, Do Hyun; Lee, Sang Soo; Lee, Danbi; Shim, Ju Hyun; Lim, Young-Suk; Lee, Han Chu; Chung, Young-Hwa; Lee, Yung Sang

2017-06-01

Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC) complicated with bile duct invasion. A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included. The majority of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and conservative management (42.9%). Among the patients with obstructive jaundice (n=88), successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively). The survival of HCC patients with bile duct invasion at initial diagnosis is generally poor. However, aggressive treatments for HCC such as resection or biliary drainage may be beneficial therapeutic options for patients with preserved liver function.

Myeloproliferative neoplasms with concurrent BCR-ABL1 translocation and JAK2 V617F mutation: a multi-institutional study from the bone marrow pathology group.

PubMed

Soderquist, Craig R; Ewalt, Mark D; Czuchlewski, David R; Geyer, Julia T; Rogers, Heesun J; Hsi, Eric D; Wang, Sa A; Bueso-Ramos, Carlos E; Orazi, Attilio; Arber, Daniel A; Hexner, Elizabeth O; Babushok, Daria V; Bagg, Adam

2018-05-01

Myeloproliferative neoplasms arise from hematopoietic stem cells with somatically altered tyrosine kinase signaling. Classification of myeloproliferative neoplasms is based on hematologic, histopathologic and molecular characteristics including the presence of the BCR-ABL1 and JAK2 V617F. Although thought to be mutually exclusive, a number of cases with co-occurring BCR-ABL1 and JAK2 V617F have been identified. To characterize the clinicopathologic features of myeloproliferative neoplasms with concomitant BCR-ABL1 and JAK2 V617F, and define the frequency of co-occurrence, we conducted a retrospective multi-institutional study. Cases were identified using a search of electronic databases over a decade at six major institutions. Of 1570 patients who were tested for both BCR-ABL1 and JAK2 V617F, six were positive for both. An additional five patients were identified via clinical records providing a total of 11 cases for detailed evaluation. For each case, clinical variables, hematologic and genetic data, and bone marrow histomorphologic features were analyzed. The sequence of identification of the genetic abnormalities varied: five patients were initially diagnosed with a JAK2 V617F+ myeloproliferative neoplasm, one patient initially had BCR-ABL1+ chronic myeloid leukemia, while both alterations were identified simultaneously in five patients. Classification of the BCR-ABL1-negative myeloproliferative neoplasms varied, and in some cases, features only became apparent following tyrosine kinase inhibitor therapy. Seven of the 11 patients showed myelofibrosis, in some cases before identification of the second genetic alteration. Our data, reflecting the largest reported study comprehensively detailing clinicopathologic features and response to therapy, show that the co-occurrence of BCR-ABL1 and JAK2 V617F is rare, with an estimated frequency of 0.4%, and most often reflects two distinct ('composite') myeloproliferative neoplasms. Although uncommon, it is important to be aware of this potentially confounding genetic combination, lest these features be misinterpreted to reflect resistance to therapy or disease progression, considerations that could lead to inappropriate management.

Primary progressive aphasia and the evolving neurology of the language network

PubMed Central

Mesulam, M.-Marsel; Rogalski, Emily J.; Wieneke, Christina; Hurley, Robert S.; Geula, Changiz; Bigio, Eileen H.; Thompson, Cynthia K.; Weintraub, Sandra

2014-01-01

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke’s area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network. PMID:25179257

Primary progressive aphasia and the evolving neurology of the language network.

PubMed

Mesulam, M-Marsel; Rogalski, Emily J; Wieneke, Christina; Hurley, Robert S; Geula, Changiz; Bigio, Eileen H; Thompson, Cynthia K; Weintraub, Sandra

2014-10-01

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke's area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network.

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

PubMed

Agrawal, Nidhi; Abbott, Collette E; Liu, Cheng; Kang, Stella; Tipton, Laura; Patel, Kepal; Persky, Mark; King, Lizabeth; Deng, Fang-Ming; Bannan, Michael; Ogilvie, Jennifer B; Heller, Keith; Hodak, Steven P

2017-04-02

Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radio-active iodine US = ultrasound.

Initial development of a computer-aided diagnosis tool for solitary pulmonary nodules

NASA Astrophysics Data System (ADS)

Catarious, David M., Jr.; Baydush, Alan H.; Floyd, Carey E., Jr.

2001-07-01

This paper describes the development of a computer-aided diagnosis (CAD) tool for solitary pulmonary nodules. This CAD tool is built upon physically meaningful features that were selected because of their relevance to shape and texture. These features included a modified version of the Hotelling statistic (HS), a channelized HS, three measures of fractal properties, two measures of spicularity, and three manually measured shape features. These features were measured from a difficult database consisting of 237 regions of interest (ROIs) extracted from digitized chest radiographs. The center of each 256x256 pixel ROI contained a suspicious lesion which was sent to follow-up by a radiologist and whose nature was later clinically determined. Linear discriminant analysis (LDA) was used to search the feature space via sequential forward search using percentage correct as the performance metric. An optimized feature subset, selected for the highest accuracy, was then fed into a three layer artificial neural network (ANN). The ANN's performance was assessed by receiver operating characteristic (ROC) analysis. A leave-one-out testing/training methodology was employed for the ROC analysis. The performance of this system is competitive with that of three radiologists on the same database.

Clinical characterization of autoimmune encephalitis and psychosis.

PubMed

Hao, Qinjian; Wang, Dahai; Guo, Lanting; Zhang, Bo

2017-04-01

Autoimmune disorders are growing alarmingly high in prevalence across the globe. Autoimmune encephalitis has had a dramatic impact on the medical field, effectually altering diagnostic and treatment paradigms in regard to neuropsychiatric disorders. Our primary goal in conducting this study was to analyze the clinical characteristics of autoimmune encephalitis patients, with special focus on psychiatric presentations, in the West China Hospital and report patient prognoses after immunotherapy. Data for patients admitted to the West China Hospital with autoimmune encephalitis diagnoses from 2015 to 2016 were collected and the corresponding clinical features were analyzed. We ultimately included 70 patients with autoimmune encephalitis: 56 (80%) anti-NMDAR encephalitis patients, 8 (11%) LGI1 antibody encephalitis patients, and 6 (9%) GABAbR antibody encephalitis patients. The median age of the 70 patients was 33years, 40% were female, and the initial symptoms in 31 patients (44%) were psychiatric in nature. Psychiatric disturbance appeared in 58 patients (83%) during inpatient treatment, after which 57 patients (81%) recovered. Many patients with autoimmune encephalitis present psychotic symptoms; psychiatric symptoms typically appear before neurological features emerge. Timely diagnosis and treatment may yield favorable prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia.

PubMed

Schneider, Tanja; Thomalla, Götz; Goebell, Einar; Piotrowski, Anna; Yousem, David Mark

2015-06-01

Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matched with the clinical history of the patient. An underlying etiology for ataxic symptoms were found in 14/18 patients (postinfectious/infectious, paraneoplastic, autoimmune, drug-induced). In two of five patients without MR imaging findings and three of eight patients with minimal imaging features (cerebellar atrophy, slight signal alterations, and small areas of restricted diffusion), adverse clinical outcomes were documented. Of the five patients with prominent MR findings (cerebellar swelling, contrast enhancement, or broad signal abnormalities), two were lost to follow-up and two showed long-term sequelae. No correlation was found between the presence of initial MRI findings in subacute or acute ataxia patients and their long-term clinical outcome. MR imaging was more flagrantly positive in cases due to encephalitis.

Phenomenology and classification of dystonia: a consensus update.

PubMed

Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B; Delong, Mahlon R; Fahn, Stanley; Fung, Victor S C; Hallett, Mark; Jankovic, Joseph; Jinnah, Hyder A; Klein, Christine; Lang, Anthony E; Mink, Jonathan W; Teller, Jan K

2013-06-15

This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during 3 in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features); and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. © 2013 Movement Disorder Society. © 2013 Movement Disorder Society.

Sarcoma of the thyroid region mimicking Riedel's thyroiditis

PubMed Central

Torres-Montaner, A; Beltran, M; d Romero; Oliva, H

2001-01-01

Because sarcomas of the anterior lower neck region occur so infrequently, they are not usually considered in the differential diagnosis of Riedel's thyroiditis. Riedel's thyroiditis itself may be confused on clinical grounds alone with malignant neoplasms because of its invasive features. Sarcomatoid carcinoma is the main entity to be discarded in this regard. This is accomplished through histological examination by the finding of carcinomatous areas and/or reactivity with epithelial markers. These features also set apart sarcomatoid carcinoma from true sarcomas. This report concerns a patient with a sarcoma of the anterior lower neck region which was initially suspected to be Riedel's thyroiditis or sarcomatoid carcinoma on clinical and radiological grounds. A peroperative biopsy was interpreted by two independent pathologists as consistent with Riedel's thyroiditis. The subsequent clinical course and postmortem examination demonstrated a high grade sarcoma with metastasis to both lungs and the pleura, and invasion of adjacent neck structures. Nevertheless, some areas of the postmortem material showed a microscopic pattern similar to mediastinal fibrosis, raising the possibility of the malignant transformation of a fibrosclerotic lesion. Key Words: Riedel's thyroiditis • sarcomatoid carcinoma • fibrous histiocytoma • differential diagnosis PMID:11429435

Clinical and prognostic significance of muscle biopsy in sarcoidosis.

PubMed

Yanardag, Halil; Tetikkurt, Cuneyt; Bilir, Muammer

2018-04-30

The main objective of this study was to evaluate the influence of muscle involvement on the clinical features, prognostic outcome, extrapulmonary organ, and endobronchial involvement in sarcoidosis patients. The second aim was to assess the diagnostic yield of muscle biopsy for the histopathologic identification of sarcoidosis.  Fifty sarcoidosis patients participated in the study. The patients were classified into two groups according to the histopathologic presence of non-caseating granulomatous inflammatory pattern of the muscle biopsy samples and were evaluated retrospectively in regard to clinical features, prognosis, extrapulmonary, and endobronchial disease involvement. Pathologic examination of the muscle biopsy samples revealed non-caseating granulomas in eighteen and myositis in seven patients compatible with sarcoidosis. The diagnostic yield of muscle biopsy for demonstrating non-caseating granulomatous inflammation was fifty percent. Patients with muscle sarcoidosis showed a worse prognosis and a more severe extrapulmonary organ involvement than the patients without muscle disease. Muscle biopsy was not statistically significant to delineate diffuse endobronchial involvement while it was suggestive for endobronchial disease clinically. The results of our study reveal that muscle biopsy appears to be a useful diagnostic tool along with its safety and easy clinical applicability. It is a rewarding utility to predict the prognostic outcome and extrapulmonary involvement in sarcoidosis patients. Positive biopsy on the other hand confirms the identification of sarcoidosis in patients with single organ involvement carrying an equivocal diagnostic clinical pattern. Muscle biopsy may be considered as the initial step for the final diagnosis of sarcoidosis in such cases.

First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?

PubMed

Baylis, Francoise; McLeod, Marcus

2017-01-01

A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed - as a result of which the quality of pre-clinical evidence is deficient - then the ethical requirement of scientific validity for clinical research may not be satisfied. In turn, this could mean that the Phase 1 clinical trial will be unsafe and that trial participants will be exposed to risk for no potential benefit. To assist sponsors, researchers, clinical investigators and reviewers in deciding when it is ethically acceptable to initiate first-in-human Phase 1 CRISPR gene editing clinical trials, structured processes have been developed to assess and minimize translational distance between pre-clinical and clinical research. These processes draw attention to various features of internal validity, construct validity, and external validity. As well, the credibility of supporting evidence is to be critically assessed with particular attention to optimism bias, financial conflicts of interest and publication bias. We critically examine the pre-clinical evidence used to justify the first-inhuman Phase 1 CRISPR gene editing cancer trial in the United States using these tools. We conclude that the proposed trial cannot satisfy the ethical requirement of scientific validity because the supporting pre-clinical evidence used to inform trial design is deficient. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Age specific fast breathing in under-five diarrheal children in an urban hospital: Acidosis or pneumonia?

PubMed

Nuzhat, Sharika; Ahmed, Tahmeed; Kawser, Chowdhury Ali; Khan, Azharul Islam; Islam, S M Rafiqul; Shahrin, Lubaba; Shahunja, K M; Shahid, Abu S M S B; Al Imran, Abdullah; Chisti, Mohammod Jobayer

2017-01-01

Children with diarrhea often present with fast breathing due to metabolic acidosis from dehydration. On the other hand, age specific fast breathing is the cornerstone for the diagnosis of pneumonia following classification of pneumonia recommended by the World Health Organization (WHO). Correction of metabolic acidosis by rehydrating the diarrheal children requires time, which delays early initiation of appropriate antimicrobials for pneumonia and thereby increases the risk of deaths. We need to further investigate the simple clinical features other than fast breathing which might help us in earliest diagnosis of pneumonia in children with diarrhea Thus, the objective of our study was to identify other contributing clinical features that may independently help for early diagnosis of pneumonia in diarrheal children who present with age specific fast breathing. This was an unmatched case-control study. Diarrheal children aged 0-59 months, admitted to Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) during January 2014 to December 2014 having age specific fast breathing (<2 month ≥60 breath/min, 2-11 months ≥50 breaths/min, >11-59 months ≥40 breaths/min) were studied. The study children with clinical and radiological pneumonia constituted the cases (n = 276) and those without pneumonia constituted the controls (n = 446). Comparison of clinical features and outcomes between the cases and the controls was made. The distribution of acidosis among the cases and the controls was comparable (35% vs. 41%, p = 0.12). The cases had proportionately higher deaths compared to the controls, however, the difference was not statistically significant (3% vs. 1%; p = 0.23). In logistic regression analysis after adjusting for potential confounders, the cases were independently associated with cough (OR = 62.19, 95% CI = 27.79-139.19; p<0.01) and chest wall indrawing (OR = 31.05, 95%CI = 13.43-71.82; p<0.01) and less often had severe acute malnutrition (OR = 0.33, 95%CI = 0.13-0.79; p<0.01). The sensitivity and specificity of cough were 83% (78-87%) and 93% (91-96%). The sensitivity and specificity for lower chest wall indrawing were 65% (59-71%) and 95% (93-97%). However, the sensitivity and specificity of cough and lower chest wall indrawing combined were 94% (89-97%) and 99% (97-100%). Thus, diarrheal children having fast breathing who present with cough and/or lower chest wall indrawing, irrespective of presence or absence of metabolic acidosis, are more likely to have radiological pneumonia. The results underscore the importance of early identification of these simple clinical features that may help to minimize potential delay due to rehydration in initiating prompt treatment of pneumonia in order to reduce fatal consequences in such children.

Cardiovascular tissue engineering: where we come from and where are we now?

PubMed

Smit, Francis E; Dohmen, Pascal M

2015-01-27

Abstract Tissue engineering was introduced by Vacanti and Langer in the 80's, exploring the potential of this new technology starting with the well-known "human ear on the mouse back". The goal is to create a substitute which supplies an individual therapy for patients with regeneration, remodeling and growth potential. The growth potential of these subjects is of special interest in congenital cardiac surgery, avoiding repeated interventions and surgery. Initial applications of tissue engineered created substitutes were relatively simple cardiovascular grafts seeded initially by end-differentiated autologous endothelial cells. Important data were collected from these initial clinical autologous endothelial cell seeded grafts in peripheral and coronary vessel disease. After these initial successfully implantation bone marrow cell were used to seed patches and pulmonary conduits were implanted in patients. Driven by the positive results of tissue engineered material implanted under low pressure circumstances, first tissue engineered patches were implanted in the systemic circulation followed by the implantation of tissue engineered aortic heart valves. Tissue engineering is an extreme dynamic technology with continuously modifications and improvements to optimize clinical products. New technologies are unified and so this has also be done with tissue engineering and new application features, so called transcatheter valve intervention. First studies are initiated to apply tissue engineered heart valves with this new transcatheter delivery system less invasive. Simultaneously studies have been started on tissue engineering of so-called whole organs since organ transplantation is restricted due to donor shortage and tissue engineering could overcome this problem. Initial studies of whole heart engineering in the rat model are promising and larger size models are initiated.

Ethnoracial Differences in the Clinical Characteristics of Alzheimer Disease at Initial Presentation at an Urban Alzheimer’s Disease Center

PubMed Central

Livney, Melissa Gartenberg; Clark, Christopher M.; Karlawish, Jason H.; Cartmell, Su; Negrón, Mirna; Nuñez-Lopez, Jessica; Xie, Sharon X.; Entenza-Cabrera, Fernando; Vega, Irving E.; Arnold, Steven E.

2010-01-01

Objective To compare presentation of Alzheimer disease (AD) at the time of initial evaluation at a university specialty clinic across three ethnoracial groups in order to understand similarities and differences in the demographic, clinical, cognitive, psychiatric, and biologic features. Design Cross-sectional study. Participants A total of 1,341 self-identified African American, Latino (primarily of Caribbean origin), and white non-Hispanic (“WNH”) subjects were recruited from primary care sites or by referral by primary care physicians. Measurements Demographic variables and age of onset of AD, as well as cognitive, functional, and mood impairments at the time of initial presentation and frequencies of apolipoprotein E genotypes, were compared across groups. Results Differences among ethnoracial groups were found for nearly all variables of interest. In particular, the largely immigrant Puerto Rican Latino group had an earlier age of onset of AD, more cognitive impairment, and greater severity of cognitive impairment at the time of initial evaluation in the setting of low average education and socioeconomic status. There was more depression in the Latinos compared with African Americans and WNHs. Greater severity of symptoms was not accounted for by a difference in lag time between onset of symptoms and initial evaluation. The apolipoprotein E-4 genotype was not associated with AD in the Latino cohort. Conclusions Minority groups in Philadelphia, especially Latinos, exhibit a more severe profile of AD at the time of presentation than WNHs. Important potential confounds need to be considered and future research comparing immigrant and nonimmigrant Latino groups will be necessary to elucidate the highly significant differences reported. PMID:21522051

Data sharing platforms for de-identified data from human clinical trials.

PubMed

Huser, Vojtech; Shmueli-Blumberg, Dikla

2018-04-01

Data sharing of de-identified individual participant data is being adopted by an increasing number of sponsors of human clinical trials. In addition to standardizing data syntax for shared trial data, semantic integration of various data elements is the focus of several initiatives that define research common data elements. This perspective article, in the first part, compares several data sharing platforms for de-identified clinical research data in terms of their size, policies and supported features. In the second part, we use a case study approach to describe in greater detail one data sharing platform (Data Share from National Institute of Drug Abuse). We present data on the past use of the platform, data formats offered, data de-identification approaches and its use of research common data elements. We conclude with a summary of current and expected future trends that facilitate secondary research use of data from completed human clinical trials.

High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial.

PubMed

Beck, Roy W; Trobe, Jonathan D; Moke, Pamela S; Gal, Robin L; Xing, Dongyuan; Bhatti, M Tariq; Brodsky, Michael C; Buckley, Edward G; Chrousos, Georgia A; Corbett, James; Eggenberger, Eric; Goodwin, James A; Katz, Barrett; Kaufman, David I; Keltner, John L; Kupersmith, Mark J; Miller, Neil R; Nazarian, Sarkis; Orengo-Nania, Silvia; Savino, Peter J; Shults, William T; Smith, Craig H; Wall, Michael

2003-07-01

To identify factors associated with a high and low risk of developing multiple sclerosis after an initial episode of optic neuritis. Three hundred eighty-eight patients who experienced acute optic neuritis between July 1, 1988, and June 30, 1991, were followed up prospectively for the development of multiple sclerosis. Consenting patients were reassessed after 10 to 13 years. The 10-year risk of multiple sclerosis was 38% (95% confidence interval, 33%-43%). Patients (160) who had 1 or more typical lesions on the baseline magnetic resonance imaging (MRI) scan of the brain had a 56% risk; those with no lesions (191) had a 22% risk (P<.001, log rank test). Among the patients who had no lesions on MRI, male gender and optic disc swelling were associated with a lower risk of multiple sclerosis, as was the presence of the following atypical features for optic neuritis: no light perception vision; absence of pain; and ophthalmoscopic findings of severe optic disc edema, peripapillary hemorrhages, or retinal exudates. The 10-year risk of multiple sclerosis following an initial episode of acute optic neuritis is significantly higher if there is a single brain MRI lesion; higher numbers of lesions do not appreciably increase that risk. However, even when brain lesions are seen on MRI, more than 40% of the patients will not develop clinical multiple sclerosis after 10 years. In the absence of MRI lesions, certain demographic and clinical features seem to predict a very low likelihood of developing multiple sclerosis. This natural history information is a critical input for estimating a patient's 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of optic neuritis or other initial demyelinating events in the central nervous system.

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study.

PubMed

Cabral, David A; Canter, Debra L; Muscal, Eyal; Nanda, Kabita; Wahezi, Dawn M; Spalding, Steven J; Twilt, Marinka; Benseler, Susanne M; Campillo, Sarah; Charuvanij, Sirirat; Dancey, Paul; Eberhard, Barbara A; Elder, Melissa E; Hersh, Aimee; Higgins, Gloria C; Huber, Adam M; Khubchandani, Raju; Kim, Susan; Klein-Gitelman, Marisa; Kostik, Mikhail M; Lawson, Erica F; Lee, Tzielan; Lubieniecka, Joanna M; McCurdy, Deborah; Moorthy, Lakshmi N; Morishita, Kimberly A; Nielsen, Susan M; O'Neil, Kathleen M; Reiff, Andreas; Ristic, Goran; Robinson, Angela B; Sarmiento, Angelyne; Shenoi, Susan; Toth, Mary B; Van Mater, Heather A; Wagner-Weiner, Linda; Weiss, Jennifer E; White, Andrew J; Yeung, Rae S M

2016-10-01

To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding. © 2016, American College of Rheumatology.

Multispectral autofluorescence diagnosis of non-melanoma cutaneous tumors

NASA Astrophysics Data System (ADS)

Borisova, Ekaterina; Dogandjiiska, Daniela; Bliznakova, Irina; Avramov, Latchezar; Pavlova, Elmira; Troyanova, Petranka

2009-07-01

Fluorescent analysis of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), keratoacanthoma and benign cutaneous lesions is carried out under initial phase of clinical trial in the National Oncological Center - Sofia. Excitation sources with maximum of emission at 365, 380, 405, 450 and 630 nm are applied for better differentiation between nonmelanoma malignant cutaneous lesions fluorescence and spectral discrimination from the benign pathologies. Major spectral features are addressed and diagnostic discrimination algorithms based on lesions' emission properties are proposed. The diagnostic algorithms and evaluation procedures found will be applied for development of an optical biopsy clinical system for skin cancer detection in the frames of National Oncological Center and other university hospital dermatological departments in our country.

Hydrometrocolpos, postaxial polydactyly, and hypothalamic hamartoma in a patient with confirmed Pallister-Hall syndrome: a clinical overlap with McKusick-Kaufman syndrome.

PubMed

Kos, Sebastian; Roth, Katharina; Korinth, Dirk; Zeilinger, Georg; Eich, Georg

2008-08-01

We present a preterm-born girl with polydactyly of both hands and massive hydrometrocolpos, the latter due to vaginal atresia. This association led initially to the diagnosis of McKusick-Kaufman syndrome (MKKS). However, additional features, including characteristic radiographic findings of the hands and a large hypothalamic tumour, presumably a hamartoma, favoured the diagnosis of Pallister-Hall syndrome (PHS), which was then genetically confirmed by detection of a GLI3 mutation (Q717X). This is the second genetically confirmed case revealing the previously described association of PHS with hydrometrocolpos due to vaginal atresia as a clinical overlap with MKKS.

Decompression sickness in a vegetarian diver: are vegetarian divers at risk? A case report.

PubMed

van Hulst, Robert A; van der Kamp, Wim

2010-01-01

We present a case of a diver who suffered decompression sickness (DCS), but who also was a strict vegetarian for more than 10 years. He presented with symptoms of tingling of both feet and left hand, weakness in both legs and sensory deficits for vibration and propriocepsis after two deep dives with decompression. The initial clinical features of this case were most consistent with DCS, possibly because of a vulnerable spinal cord due to cobalamin deficiency neuropathy. This case illustrates the similarities between DCS and a clinically defined vitamin B12 deficiency. The pathophysiology of vitamin B12 deficiency and common pathology and symptoms of DCS are reviewed.

[Pheochromocytoma and paraganglioma in childhood: a report of 2 cases report].

PubMed

Mosquera Gorostidi, A; Justo Ranera, A; Zakirian Denis, S E; González Temprano, N; Sagaseta de Ilúrdoz Uranga, M; Molina Garicano, J

2015-01-01

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors in children and most of them are sporadic. However, they represent the most common endocrine tumor in childhood, and hereditary tumor syndromes are most relevant in these age. Advances in genetic, biochemistry and imaging techniques have revised the management of these tumors; thus A biochemical study should be always initiated once the clinical diagnosis is suspected, followed by imaging and molecular studies, particularly in the context of known familial disease. The diagnostic and therapeutic features are reviewed after the presentation of two clinical cases, where the second one is a patient with type 1 Neurofibromatosis. Copyright © 2014. Published by Elsevier Espana.

Orthokeratinised odontogenic cyst mimicking periapical cyst

PubMed Central

Rajalakshmi, R; Sreeja, C; Vijayalakshmi, D; Leelarani, V

2013-01-01

Orthokeratinised odontogenic cyst (OOC) denotes the odontogenic cyst that microscopically has an orthokeratinised epithelial lining. OOC is characterised by a less-aggressive behaviour and a low rate of recurrence. This report describes a case of OOC involving posterior part of the mandible that mimicked periapical cyst in a 14-year-old boy. The initial clinical diagnosis was given as periapical cyst based on the clinical and radiographical features. Enucleation of the cyst was performed and the specimen was sent for histopathological examination. A definite diagnosis of OOC was made by histopathological examination of the biopsy specimen. This case emphases on including OOC in the differential diagnosis of radiolucencies occurring in the periapical region of non-vital tooth. PMID:24099763

Orthokeratinised odontogenic cyst mimicking periapical cyst.

PubMed

Rajalakshmi, R; Sreeja, C; Vijayalakshmi, D; Leelarani, V

2013-10-07

Orthokeratinised odontogenic cyst (OOC) denotes the odontogenic cyst that microscopically has an orthokeratinised epithelial lining. OOC is characterised by a less-aggressive behaviour and a low rate of recurrence. This report describes a case of OOC involving posterior part of the mandible that mimicked periapical cyst in a 14-year-old boy. The initial clinical diagnosis was given as periapical cyst based on the clinical and radiographical features. Enucleation of the cyst was performed and the specimen was sent for histopathological examination. A definite diagnosis of OOC was made by histopathological examination of the biopsy specimen. This case emphases on including OOC in the differential diagnosis of radiolucencies occurring in the periapical region of non-vital tooth.

Management of Patients With Histologic Transformation.

PubMed

Reddy, Nishitha M

2017-07-01

The incidence of histological transformation is up to 30% over a period of 10 years. This risk persists even beyond the initial decade of diagnosis of an indent lymphoma. In this era of emerging novel therapies, one could hope for an improved survival. There are currently no randomized trials guiding therapy for transformed lymphoma. Treatment recommendations are based on observational studies or non-randomized single arm clinical trials. To that extent, although routinely recommended and performed at transplant centers, voluminous evidence to suggest the timing or type (autologous or allogeneic) of transplant is lacking. In this article, we discuss the clinical features, treatment approach and role of stem cell transplant in transformed lymphoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary pulmonary NK/T-cell lymphoma: A case report and literature review.

PubMed

Qiu, Yajuan; Hou, Junna; Hao, Dexun; Zhang, Dandan

2018-06-01

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is an aggressive disease with poor prognosis. The lung is a relatively rare site of involvement. The current study presents a case of primary pulmonary ENKTL with fever and dyspnea, mimicking pneumonia and initially treated with empirical antibiotics. The patient demonstrated rapid deterioration and died shortly following diagnosis. To the best of our knowledge, large-scale investigations referring to primary pulmonary ENKTL are not available. As a result, the exact incidence and clinical features of primary pulmonary ENKTL are unknown. In the current report, a literature review is presented to discuss the clinical characteristics, diagnosis, treatment, and prognosis factors of this malignant disease.

Magnetization-prepared rapid acquisition with gradient echo magnetic resonance imaging signal and texture features for the prediction of mild cognitive impairment to Alzheimer's disease progression.

PubMed

Martinez-Torteya, Antonio; Rodriguez-Rojas, Juan; Celaya-Padilla, José M; Galván-Tejada, Jorge I; Treviño, Victor; Tamez-Peña, Jose

2014-10-01

Early diagnoses of Alzheimer's disease (AD) would confer many benefits. Several biomarkers have been proposed to achieve such a task, where features extracted from magnetic resonance imaging (MRI) have played an important role. However, studies have focused exclusively on morphological characteristics. This study aims to determine whether features relating to the signal and texture of the image could predict mild cognitive impairment (MCI) to AD progression. Clinical, biological, and positron emission tomography information and MRI images of 62 subjects from the AD neuroimaging initiative were used in this study, extracting 4150 features from each MRI. Within this multimodal database, a feature selection algorithm was used to obtain an accurate and small logistic regression model, generated by a methodology that yielded a mean blind test accuracy of 0.79. This model included six features, five of them obtained from the MRI images, and one obtained from genotyping. A risk analysis divided the subjects into low-risk and high-risk groups according to a prognostic index. The groups were statistically different ([Formula: see text]). These results demonstrated that MRI features related to both signal and texture add MCI to AD predictive power, and supported the ongoing notion that multimodal biomarkers outperform single-modality ones.

Early Detection of Ureteropelvic Junction Obstruction Using Signal Analysis and Machine Learning: A Dynamic Solution to a Dynamic Problem.

PubMed

Blum, Emily S; Porras, Antonio R; Biggs, Elijah; Tabrizi, Pooneh R; Sussman, Rachael D; Sprague, Bruce M; Shalaby-Rana, Eglal; Majd, Massoud; Pohl, Hans G; Linguraru, Marius George

2017-10-21

We sought to define features that describe the dynamic information in diuresis renograms for the early detection of clinically significant hydronephrosis caused by ureteropelvic junction obstruction. We studied the diuresis renogram of 55 patients with a mean ± SD age of 75 ± 66 days who had congenital hydronephrosis at initial presentation. Five patients had bilaterally affected kidneys for a total of 60 diuresis renograms. Surgery was performed on 35 kidneys. We extracted 45 features based on curve shape and wavelet analysis from the drainage curves recorded after furosemide administration. The optimal features were selected as the combination that maximized the ROC AUC obtained from a linear support vector machine classifier trained to classify patients as with or without obstruction. Using these optimal features we performed leave 1 out cross validation to estimate the accuracy, sensitivity and specificity of our framework. Results were compared to those obtained using post-diuresis drainage half-time and the percent of clearance after 30 minutes. Our framework had 93% accuracy, including 91% sensitivity and 96% specificity, to predict surgical cases. This was a significant improvement over the same accuracy of 82%, including 71% sensitivity and 96% specificity obtained from half-time and 30-minute clearance using the optimal thresholds of 24.57 minutes and 55.77%, respectively. Our machine learning framework significantly improved the diagnostic accuracy of clinically significant hydronephrosis compared to half-time and 30-minute clearance. This aids in the clinical decision making process by offering a tool for earlier detection of severe cases and it has the potential to reduce the number of diuresis renograms required for diagnosis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Recruitment experience for a pragmatic randomized controlled trial: Using EMR initiatives and minimizing research infrastructure.

PubMed

Joseph, Christine Lm; Ownby, Dennis R; Zoratti, Edward; Johnson, Dayna; Considine, Shannon; Bourgeois, Renee; Melkonian, Christina; Miree, Cheryl; Johnson, Christine Cole; Lu, Mei

2016-01-01

Modernized approaches to multisite randomized controlled trials (RCT) include the use of electronic medical records (EMR) for recruitment, remote data capture (RDC) for multisite data collection, and strategies to reduce the need for research infrastructure. These features facilitate the conduct of pragmatic trials, or trials conducted in "real life" settings. We describe the recruitment experience of an RCT to evaluate a clinic-based intervention targeting urban youth with asthma. Using encounter and prescription databases, a list of potentially-eligible patients was linked to the Epic appointment scheduling system. Patients were enrolled during a scheduled visit and then electronically randomized to a tailored versus generic online intervention. 1146 appointments for 580 eligible patients visiting 5 clinics were identified, of which 45.9% (266/580) were randomized to reach targeted enrollment (n=250). RDC facilitated multisite enrollment. Intervention content was further personalized through real- time entry of asthma medications prescribed at the clinic visit. EMR monitoring helped with recruitment trouble-shooting. Systemic challenges included a system-wide EMR transition and a system-wide reorganization of clinic staffing. Modernized RCTs can accelerate translation of research findings. Electronic initiatives facilitated implementation of this RCT; however, adaptations to recruitment strategies resulted in a more "explanatory" framework. .

Clinical analysis of 50 children with juvenile dermatomyositis.

PubMed

Kishi, Takayuki; Miyamae, Takako; Hara, Ryoki; Nakajima, Shoko; Imagawa, Tomoyuki; Mori, Masaaki; Yokota, Shumpei

2013-03-01

We performed a retrospective review of medical records to assess the clinical characteristics of 50 Japanese children with juvenile dermatomyositis (JDM). Fourteen boys and 36 girls who visited Yokohama City University Hospital between 1983 and 2008 were enrolled. Gender, age at disease onset and diagnosis, presenting clinical features, laboratory data at onset, complications, treatment, and outcome were reviewed. Mean age at disease onset was 6.9 years. Clinical manifestations at the first visit were muscle pain and/or weakness (90 %), malar rash (90 %), Gottron's papules (86 %), and heliotrope rash (80.0 %). Elevated serum levels of creatine kinase were found in 57.0 % of patients and aldolase in 95 %. T2-weighted magnetic resonance (MR) images with fat suppression demonstrated positive findings in 89.5 % of patients. Initial treatment was prednisolone (PSL) orally or pulsed methylprednisolone (mPSL) i.v. Pulsed mPSL therapy showed efficacy superior to PSL [flare in 8 of 19 (42 %) vs. 18 of 25 (72 %)]. Children refractory to initial treatment were given additional pulsed mPSL and/or cyclophosphamide (IVCY; n = 19) i.v.. Four patients with interstitial pneumonia responded well to IVCY. Our findings support the notion that JDM might be considered as both a systemic inflammatory and noninflammatory vasculopathy best treated by IVCY, as shown in previous literature.

IDH1 R132H mutation in a pilocytic astrocytoma: a case report

PubMed Central

Behling, Felix; Steinhilber, Julia; Tatagiba, Marcos; Bisdas, Sotirios; Schittenhelm, Jens

2015-01-01

We present the case of a 72-year old female with a right cerebellar pilocytic astrocytoma WHO grade I with an Isocitrate dehydrogenase 1 (IDH1) R132H mutation. The patient is recurrence-free 6 years after the initial diagnosis. Only one single case with strikingly similar clinicopathological features has been reported before. Otherwise, IDH1/2 mutations are not seen in pilocytic astrocytomas. The clinical implications of these findings are discussed. PMID:26617931

Classification of Alzheimer's disease and prediction of mild cognitive impairment-to-Alzheimer's conversion from structural magnetic resource imaging using feature ranking and a genetic algorithm.

PubMed

Beheshti, Iman; Demirel, Hasan; Matsuda, Hiroshi

2017-04-01

We developed a novel computer-aided diagnosis (CAD) system that uses feature-ranking and a genetic algorithm to analyze structural magnetic resonance imaging data; using this system, we can predict conversion of mild cognitive impairment (MCI)-to-Alzheimer's disease (AD) at between one and three years before clinical diagnosis. The CAD system was developed in four stages. First, we used a voxel-based morphometry technique to investigate global and local gray matter (GM) atrophy in an AD group compared with healthy controls (HCs). Regions with significant GM volume reduction were segmented as volumes of interest (VOIs). Second, these VOIs were used to extract voxel values from the respective atrophy regions in AD, HC, stable MCI (sMCI) and progressive MCI (pMCI) patient groups. The voxel values were then extracted into a feature vector. Third, at the feature-selection stage, all features were ranked according to their respective t-test scores and a genetic algorithm designed to find the optimal feature subset. The Fisher criterion was used as part of the objective function in the genetic algorithm. Finally, the classification was carried out using a support vector machine (SVM) with 10-fold cross validation. We evaluated the proposed automatic CAD system by applying it to baseline values from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (160 AD, 162 HC, 65 sMCI and 71 pMCI subjects). The experimental results indicated that the proposed system is capable of distinguishing between sMCI and pMCI patients, and would be appropriate for practical use in a clinical setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical Decision Support Improves Initial Dosing and Monitoring of Tobramycin and Amikacin

PubMed Central

Cox, Zachary L.; Nelsen, Cori L.; Waitman, Lemuel R.; McCoy, Jacob A.; Peterson, Josh F.

2010-01-01

Purpose Clinical decision support (CDS) systems could be valuable tools in reducing aminoglycoside prescribing errors. We evaluated the impact of CDS on initial dosing, interval, and pharmacokinetic outcomes of amikacin and tobramycin therapy. Methods A complex CDS advisor to provide guidance on initial dosing and monitoring, using both traditional and extended interval dosing strategies, was integrated into computerized provider order entry (CPOE) and compared to a control group which featured close pharmacy monitoring of all aminoglycoside orders. A random sample of 118 patients from an academic, tertiary care medical center prescribed amikacin and tobramycin prior to advisor implementation was compared to 98 patients admitted following advisor implementation. Primary outcome was an initial dose within 10% of a dose calculated to be adherent to published dose guidelines. Secondary outcomes were a guideline-adherent interval, trough and peak concentrations in goal range, and incidence of nephrotoxicity. Results Of 216 patients studied, 97 were prescribed amikacin and 119 were prescribed tobramycin. The primary outcome of initial dosing consistent with guideline-based care increased from 40% in the pre-advisor arm to 80% in the post-advisor arm (p<0.001), with a number needed to treat of 3 patients to prevent one incorrect dose. Correct initial interval based on renal function also increased from 63% to 87% (p<0.001). The changes in initial dosing and interval resulted in an increase of trough concentrations in the goal range from 59% pre-advisor to 89% post-advisor implementation (p=0.0004). There was no significant difference in peak concentrations in goal range or incidence of nephrotoxicity (25% vs. 17%, p=0.2). Conclusion An advisor for aminoglycoside dosing and monitoring integrated into CPOE significantly improves initial dosing, selection of interval, and trough concentrations at goal compared to unassisted physician dosing. PMID:21411805

Automatic classification of written descriptions by healthy adults: An overview of the application of natural language processing and machine learning techniques to clinical discourse analysis

PubMed Central

Toledo, Cíntia Matsuda; Cunha, Andre; Scarton, Carolina; Aluísio, Sandra

2014-01-01

Discourse production is an important aspect in the evaluation of brain-injured individuals. We believe that studies comparing the performance of brain-injured subjects with that of healthy controls must use groups with compatible education. A pioneering application of machine learning methods using Brazilian Portuguese for clinical purposes is described, highlighting education as an important variable in the Brazilian scenario. Objective The aims were to describe how to: (i) develop machine learning classifiers using features generated by natural language processing tools to distinguish descriptions produced by healthy individuals into classes based on their years of education; and (ii) automatically identify the features that best distinguish the groups. Methods The approach proposed here extracts linguistic features automatically from the written descriptions with the aid of two Natural Language Processing tools: Coh-Metrix-Port and AIC. It also includes nine task-specific features (three new ones, two extracted manually, besides description time; type of scene described – simple or complex; presentation order – which type of picture was described first; and age). In this study, the descriptions by 144 of the subjects studied in Toledo18 were used,which included 200 healthy Brazilians of both genders. Results and Conclusion A Support Vector Machine (SVM) with a radial basis function (RBF) kernel is the most recommended approach for the binary classification of our data, classifying three of the four initial classes. CfsSubsetEval (CFS) is a strong candidate to replace manual feature selection methods. PMID:29213908

Retinal Detachment Associated with AIDS-Related Cytomegalovirus Retinitis: Risk Factors in a Resource-Limited Setting

PubMed Central

Yen, Michael; Chen, Jenny; Ausayakhun, Somsanguan; Kunavisarut, Paradee; Vichitvejpaisal, Pornpattana; Ausayakhun, Sakarin; Jirawison, Choeng; Shantha, Jessica; Holland, Gary N; Heiden, David; Margolis, Todd P; Keenan, Jeremy D

2014-01-01

Purpose To determine risk factors predictive of retinal detachment in patients with cytomegalovirus (CMV) retinitis in a setting with limited access to ophthalmic care. Design Case-control study. Methods Sixty-four patients with CMV retinitis and retinal detachment were identified from the Ocular Infectious Diseases and Retina Clinics at Chiang Mai University. Three control patients with CMV retinitis but no retinal detachment were selected for each case, matched by calendar date. The medical records of each patient were reviewed, with patient-level and eye-level features recorded for the clinic visit used to match cases and controls, and also for the initial clinic visit at which CMV retinitis was diagnosed. Risk factors for retinal detachment were assessed separately for each of these time points using multivariate conditional logistic regression models that included 1 eye from each patient. Results Patients with a retinal detachment were more likely than controls to have low visual acuity (OR, 1.24 per line of worse vision on the logMAR scale; 95%CI, 1.16-1.33) and bilateral disease (OR, 2.12; 95%CI, 0.92-4.90). Features present at the time of the initial diagnosis of CMV retinitis that predicted subsequent retinal detachment included bilateral disease (OR, 2.68; 95%CI, 1.18-6.08) and lesion size (OR, 2.64 per 10% increase in lesion size; 95%CI, 1.41-4.94). Conclusion Bilateral CMV retinitis and larger lesion sizes, each of which is a marker of advanced disease, were associated with subsequent retinal detachment. Earlier detection and treatment may reduce the likelihood that patients with CMV retinitis develop a retinal detachment. PMID:25448999

Brown-Vialetto-Van Laere syndrome

PubMed Central

Sathasivam, Sivakumar

2008-01-01

The Brown-Vialetto-Van Laere syndrome (BVVL) is a rare neurological disorder characterized by progressive pontobulbar palsy associated with sensorineural deafness. Fifty-eight cases have been reported in just over 100 years. The female to male ratio is approximately 3:1. The age of onset of the initial symptom varies from infancy to the third decade. The syndrome most frequently presents with sensorineural deafness, which is usually progressive and severe. Lower cranial nerve involvement and lower and upper motor neuron limb signs are common neurological features. Other features include respiratory compromise (the most frequent non-neurological finding), limb weakness, slurring of speech, facial weakness, and neck and shoulder weakness. Optic atrophy, retinitis pigmentosa, macular hyperpigmentation, autonomic dysfunction, epilepsy may occur. The etiopathogenesis of the condition remains elusive. Approximately 50% of cases are familial, of which autosomal recessive is suggested. The remaining cases are sporadic. The diagnosis is usually based on the clinical presentation. Investigations (neurophysiological studies, magnetic resonance imaging of the brain, muscle biopsy, cerebrospinal fluid examination) are done to exclude other causes or to confirm the clinical findings. The differential diagnoses include the Fazio-Londe syndrome, amyotrophic lateral sclerosis, Nathalie syndrome, Boltshauser syndrome and Madras motor neuron disease. Treatment with steroids or intravenous immunoglobulin may result in temporary stabilization of the syndrome. However, the mainstays of management are supportive and symptomatic treatment, in particular assisted ventilation and maintenance of nutrition via gastrostomy. The clinical course of BVVL is variable and includes gradual deterioration (almost half of cases), gradual deterioration with stable periods in between (a third of cases) and deterioration with abrupt periods of worsening (just under a fifth of cases). After the initial presentation, one third of patients survive for ten years or longer. PMID:18416855

Retinal detachment associated with AIDS-related cytomegalovirus retinitis: risk factors in a resource-limited setting.

PubMed

Yen, Michael; Chen, Jenny; Ausayakhun, Somsanguan; Kunavisarut, Paradee; Vichitvejpaisal, Pornpattana; Ausayakhun, Sakarin; Jirawison, Choeng; Shantha, Jessica; Holland, Gary N; Heiden, David; Margolis, Todd P; Keenan, Jeremy D

2015-01-01

To determine risk factors predictive of retinal detachment in patients with cytomegalovirus (CMV) retinitis in a setting with limited access to ophthalmic care. Case-control study. Sixty-four patients with CMV retinitis and retinal detachment were identified from the Ocular Infectious Diseases and Retina Clinics at Chiang Mai University. Three control patients with CMV retinitis but no retinal detachment were selected for each case, matched by calendar date. The medical records of each patient were reviewed, with patient-level and eye-level features recorded for the clinic visit used to match cases and controls, and also for the initial clinic visit at which CMV retinitis was diagnosed. Risk factors for retinal detachment were assessed separately for each of these time points using multivariate conditional logistic regression models that included 1 eye from each patient. Patients with a retinal detachment were more likely than controls to have low visual acuity (odds ratio [OR], 1.24 per line of worse vision on the logMAR scale; 95% confidence interval [CI], 1.16-1.33) and bilateral disease (OR, 2.12; 95% CI, 0.92-4.90). Features present at the time of the initial diagnosis of CMV retinitis that predicted subsequent retinal detachment included bilateral disease (OR, 2.68; 95% CI, 1.18-6.08) and lesion size (OR, 2.64 per 10% increase in lesion size; 95% CI, 1.41-4.94). Bilateral CMV retinitis and larger lesion sizes, each of which is a marker of advanced disease, were associated with subsequent retinal detachment. Earlier detection and treatment may reduce the likelihood that patients with CMV retinitis develop a retinal detachment. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma

PubMed Central

Kim, Cha Young; Kim, Bo Ra; Lee, Sang Soo; Jeon, Dae-Hong; Lee, Chang Min; Kim, Wan Soo; Cho, Hyun Chin; Kim, Jin Joo; Lee, Jae Min; Kim, Hong Jun; Ha, Chang Yoon; Kim, Hyun Jin; Kim, Tae Hyo; Jung, Woon Tae; Lee, Ok-Jae

2017-01-01

Abstract The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC). The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development. During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P < 0.001). Initial aspartate aminotransferase levels (hazard ratio [HR] = 1.02 per 10 U/L increase, P = 0.021) and antiviral therapy (HR = 2.89, P < 0.001) were significantly associated with AFP normalization. Of the 16 (12.9%) patients who developed HCC, hepatitis B virus infection (HR = 10.82, P = 0.001), initiation of antiviral treatment postenrollment (HR = 0.23, P = 0.030), and AFP normalization within 12 months (HR = 0.13, P = 0.011) were associated with HCC development. CHB and CHC were the most common causes of falsely elevated AFP (>100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development. PMID:28079817

Acute renal infarction: Clinical characteristics and prognostic factors.

PubMed

Caravaca-Fontán, Fernando; Pampa Saico, Saúl; Elías Triviño, Sandra; Galeano Álvarez, Cristina; Gomis Couto, Antonio; Pecharromán de las Heras, Inés; Liaño, Fernando

2016-01-01

Acute renal infarction (ARI) is an uncommon disease, whose real incidence is probably higher than expected. It is associated with poor prognosis in a high percentage of cases. To describe the main clinical, biochemical and radiologic features and to determine which factors are associated with poor prognosis (death or permanent renal injury). The following is a retrospective, observational, single-hospital-based study. All patients diagnosed with ARI by contrast-enhanced computed tomography (CT) over an 18-year period were included. Patients were classified according to the cardiac or non-cardiac origin of their disease. Clinical, biochemical and radiologic features were analysed, and multiple logistic regression model was used to determine factors associated with poor prognosis. A total of 62 patients were included, 30 of which had a cardiac origin. Other 32 patients with non-cardiac ARI were younger, had less comorbidity, and were less frequently treated with oral anticoagulants. CT scans estimated mean injury extension at 35%, with no differences observed between groups. A total of 38% of patients had an unfavourable outcome, and the main determinants were: Initial renal function (OR=0.949; IC 95% 0.918-0.980; p=0.002), and previous treatment with oral anticoagulants (OR=0.135; IC 95% 0.032-0.565; p=0.006). ARI is a rare pathology with non-specific symptoms, and it is not associated with cardiological disease or arrhythmias in more than half of cases. A substantial proportion of patients have unfavourable outcomes, and the initial renal function is one of the main prognostic factors. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

The effects of variations in parameters and algorithm choices on calculated radiomics feature values: initial investigations and comparisons to feature variability across CT image acquisition conditions

NASA Astrophysics Data System (ADS)

Emaminejad, Nastaran; Wahi-Anwar, Muhammad; Hoffman, John; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael

2018-02-01

Translation of radiomics into clinical practice requires confidence in its interpretations. This may be obtained via understanding and overcoming the limitations in current radiomic approaches. Currently there is a lack of standardization in radiomic feature extraction. In this study we examined a few factors that are potential sources of inconsistency in characterizing lung nodules, such as 1)different choices of parameters and algorithms in feature calculation, 2)two CT image dose levels, 3)different CT reconstruction algorithms (WFBP, denoised WFBP, and Iterative). We investigated the effect of variation of these factors on entropy textural feature of lung nodules. CT images of 19 lung nodules identified from our lung cancer screening program were identified by a CAD tool and contours provided. The radiomics features were extracted by calculating 36 GLCM based and 4 histogram based entropy features in addition to 2 intensity based features. A robustness index was calculated across different image acquisition parameters to illustrate the reproducibility of features. Most GLCM based and all histogram based entropy features were robust across two CT image dose levels. Denoising of images slightly improved robustness of some entropy features at WFBP. Iterative reconstruction resulted in improvement of robustness in a fewer times and caused more variation in entropy feature values and their robustness. Within different choices of parameters and algorithms texture features showed a wide range of variation, as much as 75% for individual nodules. Results indicate the need for harmonization of feature calculations and identification of optimum parameters and algorithms in a radiomics study.

The Sleep Disorder in Anti-lgLON5 Disease.

PubMed

Gaig, Carles; Iranzo, Alex; Santamaria, Joan; Graus, Francesc

2018-05-23

To review the clinical and polysomnographic features of the sleep disorder occurring in the recently described anti-IgLON5 disease. The hallmark of the disease is the presence of antibodies against IgLON5, a neural cell adhesion molecule of unknown function. The disease presents a robust HLA association, and the neuropathological examination shows a novel neuronal tauopathy with predominant hypothalamic and brainstem involvement. Most patients (> 80%) present sleep-related vocalizations with movements and behaviors and sleep-disordered breathing. Polysomnographic studies show (1) a complex NREM sleep parasomnia at sleep initiation characterized by undifferentiated NREM or poorly structured N2 sleep with sleep-talking or mumbling, and simple or finalistic movements followed by normal periods of N3 or N2 NREM sleep, (2) REM sleep behavior disorder (RBD), and (3) obstructive sleep apnea with stridor. The last two features appear mainly in periods where NREM sleep normalizes. Identification of the anti-IgLON5 sleep disorder is important to suspect the disease. The combination of abnormal NREM sleep initiation, followed by normal periods of NREM sleep and RBD, represents a novel parasomnia.

Proctographic features of anismus.

PubMed

Halligan, S; Bartram, C I; Park, H J; Kamm, M A

1995-12-01

To document the proctographic features of anismus at evacuation proctography and determine the optimum radiologic measurements for diagnosis. Twenty-four patients with anismus according to clinical and multiple physiologic criteria were examined with evacuation proctography. Structural and functional measurements were compared with those of a group of 20 asymptomatic subjects. No significant difference between patients and control subjects was found with respect to pelvic descent, rectocele, or any anorectal angle measurement. In patients with anismus, initiation of evacuation was prolonged (median, 9 vs 3 seconds for control subjects; P < .0001) and anal canal width was reduced (median, 0.6 vs 1.2 cm; P = .0075). Evacuation time was increased (median, 50 vs 10 seconds; P < .0001), and the percentage of contrast material evacuated was decreased (median, 60% vs 100%; P < .0001). Only four patients were able to evacuate more than 66% of the contrast material within 30 seconds, whereas all control subjects were able to do so. Measurement of the anorectal angle to diagnose anismus should be abandoned. Patients with anismus demonstrate delayed initiation of evacuation, which is also prolonged and incomplete. Incomplete evacuation after 30 seconds is highly suggestive of anismus.

Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

PubMed Central

Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

2013-01-01

Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

Feasibility of feature-based indexing, clustering, and search of clinical trials. A case study of breast cancer trials from ClinicalTrials.gov.

PubMed

Boland, M R; Miotto, R; Gao, J; Weng, C

2013-01-01

When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.

Linear data mining the Wichita clinical matrix suggests sleep and allostatic load involvement in chronic fatigue syndrome.

PubMed

Gurbaxani, Brian M; Jones, James F; Goertzel, Benjamin N; Maloney, Elizabeth M

2006-04-01

To provide a mathematical introduction to the Wichita (KS, USA) clinical dataset, which is all of the nongenetic data (no microarray or single nucleotide polymorphism data) from the 2-day clinical evaluation, and show the preliminary findings and limitations, of popular, matrix algebra-based data mining techniques. An initial matrix of 440 variables by 227 human subjects was reduced to 183 variables by 164 subjects. Variables were excluded that strongly correlated with chronic fatigue syndrome (CFS) case classification by design (for example, the multidimensional fatigue inventory [MFI] data), that were otherwise self reporting in nature and also tended to correlate strongly with CFS classification, or were sparse or nonvarying between case and control. Subjects were excluded if they did not clearly fall into well-defined CFS classifications, had comorbid depression with melancholic features, or other medical or psychiatric exclusions. The popular data mining techniques, principle components analysis (PCA) and linear discriminant analysis (LDA), were used to determine how well the data separated into groups. Two different feature selection methods helped identify the most discriminating parameters. Although purely biological features (variables) were found to separate CFS cases from controls, including many allostatic load and sleep-related variables, most parameters were not statistically significant individually. However, biological correlates of CFS, such as heart rate and heart rate variability, require further investigation. Feature selection of a limited number of variables from the purely biological dataset produced better separation between groups than a PCA of the entire dataset. Feature selection highlighted the importance of many of the allostatic load variables studied in more detail by Maloney and colleagues in this issue [1] , as well as some sleep-related variables. Nonetheless, matrix linear algebra-based data mining approaches appeared to be of limited utility when compared with more sophisticated nonlinear analyses on richer data types, such as those found in Maloney and colleagues [1] and Goertzel and colleagues [2] in this issue.

Acute-onset chronic inflammatory demyelinating polyneuropathy: An electrodiagnostic study.

PubMed

Anadani, Mohammad; Katirji, Bashar

2015-11-01

Acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is an increasingly recognized CIDP subtype. Differentiating A-CIDP from Guillain-Barré syndrome (GBS) is challenging but important, because there are different treatment outcomes. We report 3 patients with A-CIDP who were initially diagnosed with severe GBS but were later confirmed to have CIDP based on their clinical course and electrodiagnostic (EDx) studies. We also report on the long-term treatment of these patients and review the literature on EDx studies in this syndrome. Three patients were initially diagnosed with GBS and responded to treatment. However, all 3 had arrest in improvement or deterioration during their rehabilitation phases. EDx studies showed prominent demyelinating changes many months after the initial presentation. All responded very well to immunotherapy. Although several features may suggest the diagnosis of A-CIDP at initial presentation, close follow-up of GBS patients during the recovery phase is also needed for accurate diagnosis. EDx studies may distinguish patients with A-CIDP from GBS patients. © 2015 Wiley Periodicals, Inc.

Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome.

PubMed

Lee, Jin Sook; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Chae, Jong Hee

2016-04-01

Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome. Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included. Their medical records, neuroimaging findings, and histological/biochemical findings of skeletal muscle specimens were reviewed. Targeted sequencing of mitochondrial DNA was performed based on mitochondrial respiratory chain (MRC) enzyme defects. Isolated complex I deficiency was the most frequently observed MRC defect (in 42% of 38 investigated patients). Mitochondrial DNA mutations were identified in 11 patients, of which 81.8% were MT-ND genes. The clinical outcome varied widely, from independent daily activity to severe disability. Poor functional outcomes and neurological deterioration were significantly associated with early onset (before an age of 1 year) and the presence of other lesions additional to basal ganglia involvement in the initial neuroimaging. The neurological severity and outcome of LS may vary widely and be better than those predicted based on previous studies. We suggest that age at onset and initial neuroimaging findings are prognostic indicators in LS.

[Final height in symptomatic boys with late-onset adrenal hyperplasia (LOCAH), treated with glucocorticoids. Clinical cases].

PubMed

Pasqualini, Titania; Alonso, Guillermo; Fernández, Cecilia; Buzzalino, Noemí; Dain, Liliana

2013-04-01

Although corticoid replacement is recommended for those late-onset adrenal hyperplasia with clinical manifestations, asymptomatic patients do not need treatment. We describe clinical features at diagnosis, treatment, and growth till adult- height, in 4 boys. At diagnosis, age ranged from 9.2-11.6 years. The initial symptoms/signs were: precocious pubarche (n = 2), accelerated bone age (n = 1) and precocious puberty (n = 1). All of them presented elevated 17 hydroxyprogesterone levels and were compound heterozygotes carrying p.V281L mutation. Since, at diagnosis, bone age was significantly advanced for chronological age (13.1 ± 0.5 vs. 10.2 ± 1.1 p = 0.008), hydrocortisone therapy was initiated. During follow-up, mean height Z score decreased 1.4 ± 0.4 SDS (p = 0.007), though adult mean height was not different from target height (-0.39 ± 0.7 vs. -0.04 ± 0.5 SDS, p = 0.054). In conclusion, in 4 symptomatic patients, accurate treatment of late-onset adrenal hyperplasia led to an adult mean height not different from target height. Advanced bone age at diagnosis and the loss of height during pubertal development suggest the need of therapy.

Improved initial guess with semi-subpixel level accuracy in digital image correlation by feature-based method

NASA Astrophysics Data System (ADS)

Zhang, Yunlu; Yan, Lei; Liou, Frank

2018-05-01

The quality initial guess of deformation parameters in digital image correlation (DIC) has a serious impact on convergence, robustness, and efficiency of the following subpixel level searching stage. In this work, an improved feature-based initial guess (FB-IG) scheme is presented to provide initial guess for points of interest (POIs) inside a large region. Oriented FAST and Rotated BRIEF (ORB) features are semi-uniformly extracted from the region of interest (ROI) and matched to provide initial deformation information. False matched pairs are eliminated by the novel feature guided Gaussian mixture model (FG-GMM) point set registration algorithm, and nonuniform deformation parameters of the versatile reproducing kernel Hilbert space (RKHS) function are calculated simultaneously. Validations on simulated images and real-world mini tensile test verify that this scheme can robustly and accurately compute initial guesses with semi-subpixel level accuracy in cases with small or large translation, deformation, or rotation.

Romanian adoption. The Manitoba experience.

PubMed

Benoit, T C; Jocelyn, L J; Moddemann, D M; Embree, J E

1996-12-01

To study the developmental, behavioral, and medical features in a cohort of Romanian children adopted by Manitoba families. A prospective longitudinal study. The Child Development Clinic, Children's Hospital, Winnipeg, Manitoba, from September 1990 to June 1992. Developmental, behavioral, and medical features were assessed in 22 Romanian children adopted by 18 Manitoba families. Mean (+/- SD) age at adoption was 15.5 +/- 13 months. Mean (+/- SD) age at initial assessment was 19 +/- 12 months and at follow-up, 35 +/- 13 months. Medical complications included 6 children (27%) who were positive for the hepatitis B surface antigen, 5 with intestinal parasites (23%), 1 positive for the human immunodeficiency virus, 1 with rickets (5%), and 1 with monoplegia and cleft palate (5%). Initial growth parameters were less than the fifth percentile for age for head circumference in 10 children (45%), for weight in 8 (36%), and for height in 7 (32%). At follow-up, statistically significant improvement was seen in height and weight. Initial mean (+/- SD) developmental quotients were 82 +/- 20 for gross motor, 83 +/- 23 for fine motor, 83 +/- 19 for cognitive, and 79 +/- 18 for language domains. Follow-up mean developmental quotients improved in all domains (P < .05). Twelve children (55%) displayed abnormal behavior at the initial assessment; behavioral findings persisted in 8 (36%). Initial appropriate activity level and play behavior predicted normal cognitive outcome (P < .05). This longitudinal study of Romanian adoptees delineates improvements in growth and development once the children are placed in a nurturing environment. The persistence of abnormal behavior in some children underscores the importance of further follow-up.

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

PubMed

Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

2017-05-01

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUV max ). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome

PubMed Central

Boyden, Lynn M.; Kam, Chen Y.; Hernández-Martín, Angela; Zhou, Jing; Craiglow, Brittany G.; Sidbury, Robert; Mathes, Erin F.; Maguiness, Sheilagh M.; Crumrine, Debra A.; Williams, Mary L.; Hu, Ronghua; Lifton, Richard P.; Elias, Peter M.; Green, Kathleen J.; Choate, Keith A.

2016-01-01

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin. PMID:26604139

Spatial modeling and classification of corneal shape.

PubMed

Marsolo, Keith; Twa, Michael; Bullimore, Mark A; Parthasarathy, Srinivasan

2007-03-01

One of the most promising applications of data mining is in biomedical data used in patient diagnosis. Any method of data analysis intended to support the clinical decision-making process should meet several criteria: it should capture clinically relevant features, be computationally feasible, and provide easily interpretable results. In an initial study, we examined the feasibility of using Zernike polynomials to represent biomedical instrument data in conjunction with a decision tree classifier to distinguish between the diseased and non-diseased eyes. Here, we provide a comprehensive follow-up to that work, examining a second representation, pseudo-Zernike polynomials, to determine whether they provide any increase in classification accuracy. We compare the fidelity of both methods using residual root-mean-square (rms) error and evaluate accuracy using several classifiers: neural networks, C4.5 decision trees, Voting Feature Intervals, and Naïve Bayes. We also examine the effect of several meta-learning strategies: boosting, bagging, and Random Forests (RFs). We present results comparing accuracy as it relates to dataset and transformation resolution over a larger, more challenging, multi-class dataset. They show that classification accuracy is similar for both data transformations, but differs by classifier. We find that the Zernike polynomials provide better feature representation than the pseudo-Zernikes and that the decision trees yield the best balance of classification accuracy and interpretability.

"How to have healthy children". Responses to the falling birth rate in Norway, c. 1900-1940.

PubMed

Blom, Ida

2008-01-01

This paper focuses on initiatives to improve infant health, as they developed in Norway especially during the interwar period. Falling birth rates were felt as a menace to the survival of the nation and specific initiatives were taken to oppose it. But crises engendered by the reduction in fertility strengthened opportunities for introducing policies to help the fewer children born survive and grow up to become healthy citizens. Legislation supporting mothers started in 1892 increased in the interwar years including economic features. Healthy mother and baby stations and hygienic clinics, aimed at controlling births were developed by voluntary organisations inspired from France and England respectively. A sterilization law (1934) paralleled some German policies.

Nephropathic Cystinosis Mimicking Bartter Syndrome: a Novel Mutation.

PubMed

Bastug, Funda; Nalcacioglu, Hulya; Ozaltin, Fatih; Korkmaz, Emine; Yel, Sibel

2018-01-01

Cystinosis is a rare autosomal recessive disorder resulting from defective lysosomal transport of cystine due to mutations in the cystinosin lysosomal cystine transporter (CTNS) gene. The clinical phenotype of nephropathic cystinosis is characterized by renal tubular Fanconi syndrome and development of end-stage renal disease during the first decade. Although metabolic acidosis is the classically prominent finding of the disease, a few cases may present with hypokalemic metabolic alkalosis mimicking Bartter syndrome. Bartter-like presentation may lead to delay in diagnosis and initiation of specific treatment for cystinosis. We report a case of a 6-year-old girl initially presenting with the features of Bartter syndrome that was diagnosed 2 years later with nephropathic cystinosis and a novel CTNS mutation.

Clinical and personality profiles and survival in patients with COPD.

PubMed

Ashutosh, K; Haldipur, C; Boucher, M L

1997-01-01

To assess the relationship of personality and clinical characteristics with survival in patients with advanced chronic obstructive pulmonary disease (COPD). Prospective double-blind study. Outpatient clinic of a teaching Veterans Affairs Hospital in central New York. PATIENT PARTICIPATION: Sixteen male patients (mean age, 62.2 +/- 2.5 years) with severe COPD INTERVENTIONS: Patients were administered Minnesota Multiphasic Personality Inventory (MMPI) test; their clinical features were recorded from hospital records at the time of admission into the study. All were followed up for 4 years after the initial assessment or until their death. The nine survivors and seven nonsurvivors were similar in age, pulmonary function test (PFT) results, oxygenation, number of medications, or concomitant illnesses. However, the nonsurvivors had higher MMPI and clinical illness scores compared with the survivors (p < 0.01 and < 0.05, respectively). The 4-year mortality in male veterans with severe COPD is influenced by overall psychological distress and difficulty in coping with their disease, which seem to be important prognostic indicators irrespective of PFT results or oxygenation.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with amyloid deposition: a clinicopathologic case series.

PubMed

Ryan, Russell J H; Sloan, J Mark; Collins, A Bernard; Mansouri, Jaleh; Raje, Noopur S; Zukerberg, Lawrence R; Ferry, Judith A

2012-01-01

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a mature B-cell neoplasm that typically follows an indolent clinical course. Amyloid deposition associated with MALT lymphoma is uncommon. We describe the clinical and pathologic features of 20 cases of MALT lymphoma and associated amyloid deposition across diverse primary sites. Frozen section immunofluorescence performed on 4 cases suggests that these deposits are a localized form of AL amyloid. Clinical follow-up was available for 15 patients. Amyloid deposits distant from the initial site occurred in 5 cases, always at sites also involved by the underlying lymphoma. No definitive evidence of systemic amyloidosis affecting the heart, kidneys, or liver was present in any patient. Given the generally indolent clinical behavior of MALT lymphomas with associated amyloid, we do not recommend extensive follow-up testing for systemic amyloidosis or more aggressive therapy than would be indicated for other MALT lymphomas of similar clinical stage.

[Granulomatous sporotrichosis: report of two unusual cases].

PubMed

Ramírez-Soto, Max; Lizárraga-Trujillo, José

2013-10-01

Sporotrichosis is a subcutaneous mycosis caused by Sporothrix complex, endemic in Abancay, Peru. Is acquired by traumatic inoculation with plant material. Common clinical presentations are lymphatic cutaneous and fixed cutaneous disease. We report 2 cases of fixed cutaneous sporotrichosis with granulomatous appearance. The first case was a patient of 65 years old with no risk factors and the second case was a 67 year old diabetic patient. Subjects underwent mycological culture with Sabouraud agar, with isolation of Sporothrix schenckii and clinical dignosis of fixed cutaneous sporotrichosis with granulomatous appearance. One patient received oral treatment with saturated solution of potassium iodide (SSKI) with a initial dose of 3 drops tid up to a maximum dose of 40 drops tid. Mycological and clinical cure was achieved after 2 months of treatment. We should consider the unusual clinical presentations of fixed cutaneous sporotrichosis with granulomatous appearance that present morphological and clinical features in diabetic and nondiabetic patients older than 60 years from endemic areas and communicate adequate response to treatment with SSKI in one case.

Posterior cortical atrophy variant of Alzheimer's dementia-A case report.

PubMed

Mukku, Shiva Shanker Reddy; Chintala, Haripriya; Nagaraj, Chandana; Mangalore, Sandhya; Sivakumar, Palanimuthu T; Varghese, Mathew

2018-05-17

Alzheimer's dementia (AD) is the commonest type of dementia presenting with initial episodic memory decline followed by involvement of other cognitive domains. Posterior cortical atrophy (PCA) is one of the variants of Alzheimer's dementia (AD) characterized by the atypical presentation of relatively persevered memory in the initial stage. PCA is an uncommon early onset dementia affecting adults between 50 and 65 years. It presents predominantly with visuo-spatial and visuo-perceptual deficits. PCA is a phenotype with varied etiology most common being Alzheimer's disease. The complex and atypical presentation with preserved memory and insight in patients with PCA poses challenge to clinicians in diagnosing at initial stages. There is also paucity of research on prevalence, course, prognosis and management of PCA. In this article we describe a middle aged gentlemen presenting with clinical features suggestive of PCA. We also discussed relevant literature. Copyright © 2018 Elsevier B.V. All rights reserved.

Components of visual search in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder.

PubMed

Karatekin, C; Asarnow, R F

1998-10-01

This study tested the hypotheses that visual search impairments in schizophrenia are due to a delay in initiation of search or a slow rate of serial search. We determined the specificity of these impairments by comparing children with schizophrenia to children with attention-deficit hyperactivity disorder (ADHD) and age-matched normal children. The hypotheses were tested within the framework of feature integration theory by administering children tasks tapping parallel and serial search. Search rate was estimated from the slope of the search functions, and duration of the initial stages of search from time to make the first saccade on each trial. As expected, manual response times were elevated in both clinical groups. Contrary to expectation, ADHD, but not schizophrenic, children were delayed in initiation of serial search. Finally, both groups showed a clear dissociation between intact parallel search rates and slowed serial search rates.

Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

PubMed

Tobin, W Oliver; Guo, Yong; Krecke, Karl N; Parisi, Joseph E; Lucchinetti, Claudia F; Pittock, Sean J; Mandrekar, Jay; Dubey, Divyanshu; Debruyne, Jan; Keegan, B Mark

2017-09-01

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory syndrome predominantly affecting the brainstem, cerebellum, and spinal cord. Following its initial description, the salient features of CLIPPERS have been confirmed and expanded upon, but the lack of formalized diagnostic criteria has led to reports of patients with dissimilar features purported to have CLIPPERS. We evaluated clinical, radiological and pathological features of patients referred for suspected CLIPPERS and propose diagnostic criteria to discriminate CLIPPERS from non-CLIPPERS aetiologies. Thirty-five patients were evaluated for suspected CLIPPERS. Clinical and neuroimaging data were reviewed by three neurologists to confirm CLIPPERS by consensus agreement. Neuroimaging and neuropathology were reviewed by experienced neuroradiologists and neuropathologists, respectively, both of whom were blinded to the clinical data. CLIPPERS was diagnosed in 23 patients (18 male and five female) and 12 patients had a non-CLIPPERS diagnosis. CLIPPERS patients' median age of onset was 58 years (interquartile range, 24-72) and were followed a median of 44 months (interquartile range 38-63). Non-CLIPPERS patients' median age of onset was 52 years (interquartile range, 39-59) and were followed a median of 27 months (interquartile range, 14-47). Clinical symptoms of gait ataxia, diplopia, cognitive impairment, and facial paraesthesia did not discriminate CLIPPERS from non-CLIPPERS. Marked clinical and radiological corticosteroid responsiveness was observed in CLIPPERS (23/23), and clinical worsening occurred in all 12 CLIPPERS cases when corticosteroids were discontinued. Corticosteroid responsiveness was common but not universal in non-CLIPPERS [clinical improvement (8/12); radiological improvement (2/12); clinical worsening on discontinuation (3/8)]. CLIPPERS patients had brainstem predominant perivascular gadolinium enhancing lesions on magnetic resonance imaging that were discriminated from non-CLIPPERS by: homogenous gadolinium enhancing nodules <3 mm in diameter without ring-enhancement or mass effect, and homogenous T2 signal abnormality not significantly exceeding the T1 enhancement. Brain neuropathology on 14 CLIPPERS cases demonstrated marked CD3-positive T-lymphocyte, mild B-lymphocyte and moderate macrophage infiltrates, with perivascular predominance as well as diffuse parenchymal infiltration (14/14), present in meninges, white and grey matter, associated with variable tissue destruction, astrogliosis and secondary myelin loss. Clinical, radiological and pathological feature define CLIPPERS syndrome and are differentiated from non-CLIPPERS aetiologies by neuroradiological and neuropathological findings. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Incidence of right-sided colonic tumors (non-appendiceal) in patient's ≥40 years of age presenting with features of acute appendicitis.

PubMed

Khan, Suhail Aslam; Khokhar, Haseeb Anwar; Nasr, A R H; Carton, Eleanor

2013-01-01

Non-appendiceal tumors can mimic and present with clinical features of acute appendicitis in patients of age 40 years or above. The aim of this prospective study is to investigate the incidence of right-sided (non-appendiceal) colonic tumors in patients presenting with clinical features of acute appendicitis. A prospective data analysis of 1662 patients using appendectomy database was performed from 2005 to 2011. Patients above age 40 years or older were included. Patients were compared for demographic data, clinical presentation, radiological findings, operative technique & findings, histo-pathological findings and postoperative complications. The primary outcome was incidence of right-sided colonic (non-appendiceal) tumors presenting with features of acute appendicitis. Secondary outcomes measured were, role of diagnostic radiology, negative appendectomy rate, length of stay and changing trends in operative techniques. From 1662 patients initially reviewed, only 179 patients (10.77%) age 40 years or above mean (56 ± 11.75), median 54 (40-89), with clinical features of acute appendicitis were included in the final analysis. F:M ratio was (1:1.06). CT scan showed in only 1 patient (1.25%, OR = 0.806, p = 0.695), suspicion of cecal tumor and underwent right hemicolectomy. Histological examination of specimen showed, 2 patients (1.11%, OR = 1.10, p = 0.47) had primary appendiceal tumors, in which one patient was histologically reported as appendiceal mucocele (mucinous cystadenoma with low-grade dysplasia), while the other one had appendeceal carcinoid (Goblet cell carcinoid). In the other tumor group one patient had metastatic involvement of appendix from ovarian tumor. The time to appendectomy in radiological group was delayed by (9.2 ± 3.7 h). 131 (73.1%) had laparoscopic while 48 (26.81%) underwent open appendectomy. The negative appendectomy rate was (1.12%) and 30 days complication rate was (11.73%, p = 0.27). Mean length of stay was 3.54 ± 2.1 days. Right-sided colonic (cecal) tumors rarely present with features of acute appendicitis. Only those patients with atypical presentation and findings should have pre-operative radiological evaluation. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Identifying clinical features in primary care electronic health record studies: methods for codelist development.

PubMed

Watson, Jessica; Nicholson, Brian D; Hamilton, Willie; Price, Sarah

2017-11-22

Analysis of routinely collected electronic health record (EHR) data from primary care is reliant on the creation of codelists to define clinical features of interest. To improve scientific rigour, transparency and replicability, we describe and demonstrate a standardised reproducible methodology for clinical codelist development. We describe a three-stage process for developing clinical codelists. First, the clear definition a priori of the clinical feature of interest using reliable clinical resources. Second, development of a list of potential codes using statistical software to comprehensively search all available codes. Third, a modified Delphi process to reach consensus between primary care practitioners on the most relevant codes, including the generation of an 'uncertainty' variable to allow sensitivity analysis. These methods are illustrated by developing a codelist for shortness of breath in a primary care EHR sample, including modifiable syntax for commonly used statistical software. The codelist was used to estimate the frequency of shortness of breath in a cohort of 28 216 patients aged over 18 years who received an incident diagnosis of lung cancer between 1 January 2000 and 30 November 2016 in the Clinical Practice Research Datalink (CPRD). Of 78 candidate codes, 29 were excluded as inappropriate. Complete agreement was reached for 44 (90%) of the remaining codes, with partial disagreement over 5 (10%). 13 091 episodes of shortness of breath were identified in the cohort of 28 216 patients. Sensitivity analysis demonstrates that codes with the greatest uncertainty tend to be rarely used in clinical practice. Although initially time consuming, using a rigorous and reproducible method for codelist generation 'future-proofs' findings and an auditable, modifiable syntax for codelist generation enables sharing and replication of EHR studies. Published codelists should be badged by quality and report the methods of codelist generation including: definitions and justifications associated with each codelist; the syntax or search method; the number of candidate codes identified; and the categorisation of codes after Delphi review. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical Predictors and Outcome of Metabolic Acidosis in Under-Five Children Admitted to an Urban Hospital in Bangladesh with Diarrhea and Pneumonia

PubMed Central

Chisti, Mohammod J.; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, A. S. G.; Bardhan, Pradip K.; Dey, Sanjoy Kumer; Huq, Sayeeda; Das, Sumon Kumar; Salam, Mohammed A.

2012-01-01

Background Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. Methods We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). Results Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62–7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01–1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. Conclusion and Significance Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the diagnostic clinical features of radiological pneumonia which underscores the importance of early initiation of appropriate antibiotics to combat morbidity and deaths in such population. PMID:22720060

Evaluation of cystoid change phenotypes in ocular toxoplasmosis using optical coherence tomography.

PubMed

Ouyang, Yanling; Pleyer, Uwe; Shao, Qing; Keane, Pearse A; Stübiger, Nicole; Joussen, Antonia M; Sadda, Srinivas R; Heussen, Florian M

2014-01-01

To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT). Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT. Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality. In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise "normal" looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis.

Evaluation of Cystoid Change Phenotypes in Ocular Toxoplasmosis Using Optical Coherence Tomography

PubMed Central

Shao, Qing; Keane, Pearse A.; Stübiger, Nicole; Joussen, Antonia M.; Sadda, Srinivas R.; Heussen, Florian M.

2014-01-01

Purpose To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT). Methods Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT. Results Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality. Conclusions In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise “normal” looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis. PMID:24505261

XP11.2 translocation renal cell carcinoma: clinical experience of Taipei Veterans General Hospital.

PubMed

Hung, Chia-Chen; Pan, Chin-Chen; Lin, Chih-Chieh; Lin, Alex T L; Chen, Kuang-Kuo; Chang, Yen-Hwa

2011-11-01

Xp11.2 translocation renal cell carcinoma (RCC), a recently recognized distinct subtype of RCC, is characterized by various translocations, all involving the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults and comprise about one-third of pediatric RCCs. In the present study, we review the clinical course of Xp11.2 translocation renal cell carcinoma in our institution. We identified eight cases with Xp11.2 translocation RCC between 2007 and 2010 from the pathological archives of the Taipei Veterans General Hospital. We retrospectively analyzed the patients' characteristics, clinical manifestations, and specific pathological features for definitive diagnosis, surgical and systemic treatment and clinical outcome of these rare cancers. Patients were aged 20 years to 49 years (mean age 28 years) with female predominance (6 females, 2 males). One patient presented with asymptomatic renal mass detected incidentally during abdominal sonography. Four patients complained of flank or abdominal pain, and the other three complained of gross hematuria at initial presentation. The mean tumor size was 9.2 cm (range, 4 cm-17 cm). Seven patients underwent radical nephrectomy for the primary tumor, while one presented with multiple metastases. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of tumors with TFE3 gene fusion, which showed positive nuclear staining. Three patients presented initially with metastatic diseases, and another three patients progressed to lung, liver and bone metastases at eight, seven and nine months postoperatively. Although RT-PCR and DNA sequencing are the final diagnoses of the molecular identity of Xp11.2 translocation RCC, experienced pathologists could confirm the histologic diagnosis based on the distinctive morphologic features with positive TFE3 immunochemical nuclear stain. Surgical resection is the only treatment. The role of systemic therapy for local recurrence and metastasis remains to be determined. Copyright © 2011. Published by Elsevier B.V.

Competitive Advantage of PET/MRI

PubMed Central

Jadvar, Hossein; Colletti, Patrick M.

2013-01-01

Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. PMID:23791129

Competitive advantage of PET/MRI.

PubMed

Jadvar, Hossein; Colletti, Patrick M

2014-01-01

Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Control of mediolateral stability during rapid step initiation with preferred and non-preferred leg: is it symmetrical?

PubMed

Yiou, E; Do, M C

2010-05-01

During voluntary stepping initiation, postural stability along the mediolateral direction is controlled via "anticipatory postural adjustment" (APA). This study tested the hypothesis that, in young healthy subjects, the biomechanical features of mediolateral APA depend on the leg that initiates stepping. Subjects (N=10) initiated a rapid single step with the preferred (P condition) and the non-preferred leg (NP condition) on a force-plate. Results showed that mediolateral APA duration (P=0.020) and amplitude were higher (as attested by the increase in maximal center-of-gravity velocity (P=0.003) and displacement (P<0.001) during APA), and that mediolateral stability was better (as attested by the attenuation in center-of-gravity velocity at time of swing-foot contact (P=0.007)) in P than in NP. These results support the view that stepping initiation in healthy subjects involves postural asymmetry. This statement may have relevant implications in clinical evaluation where postural asymmetry is generally considered as reflecting postural impairment. Copyright 2010 Elsevier B.V. All rights reserved.

Cholera in pregnancy: Clinical and immunological aspects.

PubMed

Khan, Ashraful I; Chowdhury, Fahima; Leung, Daniel T; Larocque, Regina C; Harris, Jason B; Ryan, Edward T; Calderwood, Stephen B; Qadri, Firdausi

2015-10-01

The objective of this study was to examine the clinical and immunological features of cholera in pregnancy. Women of reproductive age presenting to the icddr,b Dhaka hospital with cholera, and enrolled as part of a larger cohort study, were tested for pregnancy on admission. We compared initial clinical features and immune responses of pregnant patients with non-pregnant female patients at days 2, 7 and 21 after infection. Among reproductive age women enrolled between January 2001 and May 2006, 9.7% (14/144) were pregnant. The duration of diarrhoea prior to admission tended to be higher in pregnant compared to non-pregnant patients (p=0.08), but other clinical characteristics did not differ. Antibody responses to cholera toxin B subunit (CtxB), toxin-coregulated pilus A (TcpA), Vibrio cholerae lipopolysaccharide (LPS), and serum vibriocidal antibody responses, were comparable between pregnant and non-pregnant patients. There were no deaths among the pregnant cases or non-pregnant controls, and no adverse foetal outcomes, including stillbirths, during 21 days of follow up of pregnant cases. To our knowledge, this is the first report of immune responses in pregnant women with cholera. We found that pregnant woman early in pregnancy has comparable clinical illness and subsequent immune responses compared to non-pregnant women. These findings suggest that the evaluation of safety and immunogenicity of oral cholera vaccines in pregnancy should be an area of future investigations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Survival with Three-Times Weekly In-Center Nocturnal Versus Conventional Hemodialysis

PubMed Central

Xu, Jianglin; Suri, Rita S.; Nesrallah, Gihad; Lindsay, Robert; Garg, Amit X.; Lester, Keith; Ofsthun, Norma; Lazarus, Michael; Hakim, Raymond M.

2012-01-01

Whether the duration of hemodialysis treatments improves outcomes remains controversial. Here, we evaluated survival and clinical changes associated with converting from conventional hemodialysis (mean=3.75 h/treatment) to in-center nocturnal hemodialysis (mean=7.85 h/treatment). All 959 consecutive patients who initiated nocturnal hemodialysis for the first time in 77 Fresenius Medical Care facilities during 2006 and 2007 were eligible. We used Cox models to compare risk for mortality during 2 years of follow-up in a 1:3 propensity score–matched cohort of 746 nocturnal and 2062 control patients on conventional hemodialysis. Two-year mortality was 19% among nocturnal hemodialysis patients compared with 27% among conventional patients. Nocturnal hemodialysis associated with a 25% reduction in the risk for death after adjustment for age, body mass index, and dialysis vintage (hazard ratio=0.75, 95% confidence interval=0.61–0.91, P=0.004). With respect to clinical features, interdialytic weight gain, albumin, hemoglobin, dialysis dose, and calcium increased on nocturnal therapy, whereas postdialysis weight, predialysis systolic blood pressure, ultrafiltration rate, phosphorus, and white blood cell count declined (all P<0.001). In summary, notwithstanding the possibility of residual selection bias, conversion to treatment with nocturnal hemodialysis associates with favorable clinical features, laboratory biomarkers, and improved survival compared with propensity score–matched controls. The potential impact of extended treatment time on clinical outcomes while maintaining a three times per week hemodialysis schedule requires evaluation in future clinical trials. PMID:22362905

A Clinic-based Survey of Clinical Characteristics and Practice Pattern of Dry Eye in Japan.

PubMed

Kawashima, Motoko; Yamada, Masakazu; Suwaki, Kazuhisa; Shigeyasu, Chika; Uchino, Miki; Hiratsuka, Yoshimune; Yokoi, Norihiko; Tsubota, Kazuo

2017-03-01

The aim of this study was to investigate the clinical characteristics and practice pattern of patients with dry eye disease (DED) in eye clinics across Japan. A multi-center, cross-sectional study was conducted among patients with DED who visited eye clinics in Japan. Subjective symptoms, patient's background, ocular surface features, and tear function were evaluated. Main outcome measures were tear break-up time (TBUT), Schirmer I value, kerato-conjunctival staining score, and dry eye symptom questionnaire score. Initially, 463 subjects were enrolled, and 449 cases (63 male and 386 female; mean age, 62.6 ± 15.7 years) were included in the final analysis. Overall, 94.9% of patients had a shortened TBUT (≤5 s), and 54.6% had an aqueous tear deficiency (Schirmer I value ≤5 mm). The most prevalent subtype of dry eye was aqueous-deficient dry eye, which was present in 35.0% of all patients, followed by short-BUT-type dry eye, which was seen in 26.7%. The two most common DED subtypes were aqueous-deficient and short-BUT-type dry eye. Shortened TBUT is the most common feature of dry eye, regardless of subtype. The current treatment choice mainly consisted of hyaluronic acid, two novel mucin secretagogues, diquafosol and rebamipide, and steroidal eye drops. University Hospital Medical Information Network: UMIN (registries no. UMIN 000015890). Japan Dry Eye Society, Tokyo, Japan, and Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study.

PubMed

Krupp, Lauren B; Pohl, Daniela; Ghezzi, Angelo; Boyko, Alexey; Tenembaum, Silvia; Chen, Liang; Aycardi, Ernesto; Banwell, Brenda

2016-04-15

To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon β-1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [<12 years] and adolescents [12-17 years]). US adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5 kg/m(2)), started disease-modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon β-1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon β-1a to another DMT before the end of the observation period. This retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon β-1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Model-based and Model-free Machine Learning Techniques for Diagnostic Prediction and Classification of Clinical Outcomes in Parkinson's Disease.

PubMed

Gao, Chao; Sun, Hanbo; Wang, Tuo; Tang, Ming; Bohnen, Nicolaas I; Müller, Martijn L T M; Herman, Talia; Giladi, Nir; Kalinin, Alexandr; Spino, Cathie; Dauer, William; Hausdorff, Jeffrey M; Dinov, Ivo D

2018-05-08

In this study, we apply a multidisciplinary approach to investigate falls in PD patients using clinical, demographic and neuroimaging data from two independent initiatives (University of Michigan and Tel Aviv Sourasky Medical Center). Using machine learning techniques, we construct predictive models to discriminate fallers and non-fallers. Through controlled feature selection, we identified the most salient predictors of patient falls including gait speed, Hoehn and Yahr stage, postural instability and gait difficulty-related measurements. The model-based and model-free analytical methods we employed included logistic regression, random forests, support vector machines, and XGboost. The reliability of the forecasts was assessed by internal statistical (5-fold) cross validation as well as by external out-of-bag validation. Four specific challenges were addressed in the study: Challenge 1, develop a protocol for harmonizing and aggregating complex, multisource, and multi-site Parkinson's disease data; Challenge 2, identify salient predictive features associated with specific clinical traits, e.g., patient falls; Challenge 3, forecast patient falls and evaluate the classification performance; and Challenge 4, predict tremor dominance (TD) vs. posture instability and gait difficulty (PIGD). Our findings suggest that, compared to other approaches, model-free machine learning based techniques provide a more reliable clinical outcome forecasting of falls in Parkinson's patients, for example, with a classification accuracy of about 70-80%.

[Features associated with retinal thickness extension in diabetic macular oedema].

PubMed

Razo Blanco-Hernández, Dulce Milagros; Lima-Gómez, Virgilio; García-Rubio, Yatzul Zuhaila

2015-01-01

Clinically significant macular edema has features that are associated with a major risk of visual loss, with thickening that involves the centre of the macula, field 7 or visual deficiency, although it is unknown if these features are related to retinal thickness extension. An observational, analytical, prospective, cross-sectional and open study was conducted. The sample was divided into initial visual acuity ≥0.5, central field thickness, center point thickness, field 7 and macular volume more than the reported 2 standard deviation mean value in eyes without retinopathy. The extension was determined by the number of the central field area equivalent thickening and these features were compared with by Student's t test for independent samples. A total of 199 eyes were included. In eyes with visual acuity of ≥0.5, the mean extension was 2.88±1.68 and 3.2±1.63 in area equivalent in eyes with visual acuity <0.5 (p=0.12). The mean extension in eyes with less than 2 standard deviation of central field thickness, center point thickness, field 7 and macular volume was significantly lower than in eyes with more than 2 standard deviations (1.9±0.93 vs. 4.07±1.49, 2.44±1.47 vs. 3.94±1.52, 1.79±1.07 vs. 3.61±1.57 and 1.6±0.9 vs. 3.9±1.4, respectively, p<0.001). The extension of retinal thickness is related with the anatomical features reported with a greater risk of visual loss, but is not related to initial visual deficiency. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Automatic initialization and quality control of large-scale cardiac MRI segmentations.

PubMed

Albà, Xènia; Lekadir, Karim; Pereañez, Marco; Medrano-Gracia, Pau; Young, Alistair A; Frangi, Alejandro F

2018-01-01

Continuous advances in imaging technologies enable ever more comprehensive phenotyping of human anatomy and physiology. Concomitant reduction of imaging costs has resulted in widespread use of imaging in large clinical trials and population imaging studies. Magnetic Resonance Imaging (MRI), in particular, offers one-stop-shop multidimensional biomarkers of cardiovascular physiology and pathology. A wide range of analysis methods offer sophisticated cardiac image assessment and quantification for clinical and research studies. However, most methods have only been evaluated on relatively small databases often not accessible for open and fair benchmarking. Consequently, published performance indices are not directly comparable across studies and their translation and scalability to large clinical trials or population imaging cohorts is uncertain. Most existing techniques still rely on considerable manual intervention for the initialization and quality control of the segmentation process, becoming prohibitive when dealing with thousands of images. The contributions of this paper are three-fold. First, we propose a fully automatic method for initializing cardiac MRI segmentation, by using image features and random forests regression to predict an initial position of the heart and key anatomical landmarks in an MRI volume. In processing a full imaging database, the technique predicts the optimal corrective displacements and positions in relation to the initial rough intersections of the long and short axis images. Second, we introduce for the first time a quality control measure capable of identifying incorrect cardiac segmentations with no visual assessment. The method uses statistical, pattern and fractal descriptors in a random forest classifier to detect failures to be corrected or removed from subsequent statistical analysis. Finally, we validate these new techniques within a full pipeline for cardiac segmentation applicable to large-scale cardiac MRI databases. The results obtained based on over 1200 cases from the Cardiac Atlas Project show the promise of fully automatic initialization and quality control for population studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

PubMed

Kim, Bo Eun; Koh, Kyung-Nam; Suh, Jin Kyung; Im, Ho Joon; Song, Joon Sup; Lee, Ji Won; Kang, Hyoung Jin; Park, Kyung Duck; Shin, Hee Young; Choi, Hyoung Soo; Lee, Soo Hyun; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe; Jung, Hye Lim; Chung, Nak-Gyun; Cho, Bin; Kim, Hack Ki; Lyu, Chuhl Joo; Baek, Hee Jo; Kook, Hoon; Park, Jun Eun; Park, Hyeon Jin; Park, Byung-Kiu; Yoo, Eun Sun; Ryu, Kyung Ha; Lee, Kun Soo; Kim, Heung Sik; Lee, Jae Min; Park, Eun Sil; Yoon, Hoi Soo; Lee, Kwang Chul; Lee, Mee Jeong; Lim, Young Tak; Kim, Hwang Min; Park, Sang Kyu; Park, Jeong-A; Kim, Soon Ki; Park, Meerim; Lim, Yeon-Jung; Lee, Young Ho; Seo, Jong Jin

2014-03-01

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.

Chinese culture permeation in the treatment of Parkinson disease: a cross-sectional study in four regions of China.

PubMed

Zhang, Zhen-Xin; Chen, Honglei; Chen, Sheng-Di; Shao, Ming; Sun, Sheng-Gang; Qu, Qiu-Min; Zhang, Bao-Rong; Liu, Yi-Ming; Xu, Qun; Wan, Xia; Li, Ling; Wen, Hong-Bo; Chen, Xia; Chen, Hai-Bo; Liu, Zhen-Guo; Wang, Jian; Wang, Gang

2014-01-30

Little is known about the clinical features and treatment of Chinese patients with Parkinson disease (PD). A large cross-sectional survey of clinical features, medication use, and motor complications was conducted in 901 consecutive PD patients, from 42 randomly selected university-affiliated hospitals in four urban economic regions of China, between December 2006 and May 2007. The 901 PD patients had age range 30 to 88, and median disease duration 50 months. Most (737, 81.8%) used L-dopa (median 375 mg/day), and often added low doses of other antiparkinsonian agents. Among L-dopa-treated patients, the prevalence of motor complications was low (dyskinesias: 8.5%; motor fluctuations: 18.6%), even among patients with disease duration ≥11 years (dyskinesias: 18.1%; motor fluctuations: 42.2%). Higher L-dopa use was associated with higher occurrence of dyskinesias (OR 2.44; 95% CI 1.20-5.13) and motor fluctuations (OR 2.48; 95% CI 1.49-4.14). Initiating PD treatment with L-dopa alone (OR 0.46; 95% CI 0.22-0.95) or in combination with other medications (OR 0.41; 95% CI 0.19-0.87) was associated with less dyskinesia than treatment initiated with non-L-dopa medication. Many Chinese PD patients are treated with low-dose L-dopa and added low-dose antiparkinsonian agents, with a low prevalence of motor complications, which might be influenced by Chinese culture.

Features of Hepatitis in Hepatitis-associated Aplastic Anemia: Clinical and Histopathologic Study.

PubMed

Patel, Kalyani R; Bertuch, Alison; Sasa, Ghadir S; Himes, Ryan W; Wu, Hao

2017-01-01

Hepatitis-associated aplastic anemia (HAA) is a rare variant of aplastic anemia in which patients present with severe pancytopenia after an episode of acute hepatitis. The marrow failure is often rapid, severe, and usually fatal if untreated. The preceding hepatitis is largely under-studied. Retrospective study of the clinical and histopathologic features of hepatitis in pediatric patients who subsequently developed aplastic anemia and comparison with consecutive cases of acute liver failure and random cases of autoimmune hepatitis during the same time frame. All 7 patients of HAA had significant elevations in aminotransferases and conjugated hyperbilirubinemia at initial presentation. Echoing liver function indices, cholestatic hepatitis with sinusoidal obstruction-type endothelial injury was seen histomorphologically. Autoimmune hepatitis serology such as anti-F-actin, anti-liver/kidney microsome, and hypergammaglobulinemia was negative in all patients. Five of 7 patients (71.4%) had, however, elevated antinuclear antibody, all with a speckled pattern. Hepatitis virus serology was negative in all patients. By immunohistochemical staining, the lobular CD8/CD4 lymphocyte ratio was markedly elevated in all of the initial samples with significant reduction in this ratio (P = 0.03) in 3 patients post treatment (ursodiol, antibiotics, and/or immunosuppressive therapy). Hepatitis preceding HAA is characterized by marked elevation of aminotransferases, conjugated hyperbilirubinemia, elevated antinuclear antibody with a speckled pattern, cholestatic hepatitis with sinusoidal obstruction morphology, and CD8 dominant lobular infiltrates. The present study suggests HAA may result from cytotoxic T-cell-mediated sinusoidal endothelial and hepatocytic injury.

Clinical and radiological features of synchronous pure ground-glass nodules observed along with operable non-small cell lung cancer.

PubMed

Dai, Chenyang; Ren, Yijiu; Xie, Huikang; Jiang, Sen; Fei, Ke; Jiang, Gening; Chen, Chang

2016-06-01

It is common to observe synchronous pure ground-glass nodules (PGN) along with operable primary tumor on initial CT scans while clinical and radiological features of these PGNs remain unclear. We included patients with primary tumor and PGNs detected between June 2010 and December 2013 retrospectively. The radiographic manifestations of all PGNs, pathologic findings of resected PGNs, and follow-up outcomes of unresected PGNs were analyzed to determine the predictors of malignant PGNs. Overall, 84 PGNs in 71 patients were included, of which 41 were resected at primary surgery and 43 were followed up. In resected group, there were 17 carcinomatous PGNs, 11 atypical adenomatous hyperplasia, and 13 benign lesions. In a follow-up group, 7 out of 43 PGNs grew, out of which four PGNs were diagnosed as adenocarcinoma and the remaining three PGNs were still followed up. In univariate analysis, size (P < 0.001), air bronchogram (P = 0.001), bubble lucency (P = 0.038), and pleural tag (P = 0.004) were the factors for malignant potential of PGNs. Multivariate analysis showed that size was an independent risk factor (P = 0.005), and the cut-off value was 9.4 mm. The initial size and imaging signs may be useful in assessing the malignant potential of synchronous PGNs before surgery. J. Surg. Oncol. 2016;113:738-744. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Clinical features and outcomes of patients with hepatocellular carcinoma complicated with bile duct invasion

PubMed Central

An, Jihyun; Lee, Kwang Sun; Park, Do Hyun; Lee, Sang Soo; Lee, Danbi; Shim, Ju Hyun; Lim, Young-Suk; Lee, Han Chu; Chung, Young-Hwa; Lee, Yung Sang

2017-01-01

Background/Aims Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC) complicated with bile duct invasion. Methods A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included. Results The majority of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and conservative management (42.9%). Among the patients with obstructive jaundice (n=88), successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively). Conclusions The survival of HCC patients with bile duct invasion at initial diagnosis is generally poor. However, aggressive treatments for HCC such as resection or biliary drainage may be beneficial therapeutic options for patients with preserved liver function. PMID:28506055

Malformations of cortical development: clinical spectrum in a series of 101 patients and review of the literature (Part I).

PubMed

Güngör, Serdal; Yalnizoğlu, Dilek; Turanli, Güzide; Saatçi, Işil; Erdoğan-Bakar, Emel; Topçu, Meral

2007-01-01

Patients with malformations of cortical development (MCD) present with a wide spectrum of clinical manifestations ranging from asymptomatic cases to those with epilepsy and neurodevelopmental problems. Thorough clinical delineation of patients with MCD may provide clues for future phenotype-genotype correlation studies. We studied clinical features of patients with MCD, including developmental risk factors and family history. We evaluated 10 patients with MCD at Hacettepe University Children's Hospital, Department of Pediatric Neurology. All patients underwent neurological evaluation with detailed medical and family history, and neuropsychological evaluation. Routine EEG and MRI were obtained. The patients were between 1 month and 19 years of age (mean: 6.1 +/- 4.4 years). Fifty-four patients were diagnosed with polymicrogyria (PMG), 23 patients with lissencephaly, 12 patients with schizencephaly, and 12 patients with heterotopia. Parents were relatives in 31.7% of the cases; consanguinity was most common in patients with lissencephaly and other MCDs with diffuse/bilateral involvement. Initial clinical presentation was seizures in 61.4% of the cases, developmental delays in 12.9%, and microcephaly in 9.9%. Neurological evaluation revealed most severe abnormalities in patients with lissencephaly, and relatively better outcome in patients with heterotopias. Cognitive functions were better in patients with heterotopias compared to other groups. Overall, 71.3% of patients ha epilepsy. In conclusion, initial presentation and clinical course of patients with MCD are variable and seem to be correlated with the extent of cortical involvement. Epilepsy and mental retardation are the most common problems. The most severe clinical outcome was seen in patients with lissencephaly.

Higher Growth Rate of Branch Duct Intraductal Papillary Mucinous Neoplasms Associates With Worrisome Features.

PubMed

Kolb, Jennifer M; Argiriadi, Pamela; Lee, Karen; Liu, Xiaoyu; Bagiella, Emilia; Lucas, Aimee L; Kim, Michelle Kang; Kumta, Nikhil A; Nagula, Satish; Sarpel, Umut; DiMaio, Christopher J

2018-03-11

For patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs, cysts), it is a challenge to identify those at high risk for malignant lesions. We sought to identify factors associated with development of pancreatic cancer, focusing on neoplasm growth rate. We performed a retrospective study of 189 patients with BD-IPMNs who underwent at least 2 contrast-enhanced cross-sectional imaging studies, 1 year or more apart, at a tertiary referral center from January 2003 through 2013. Patients with cysts that had Fukuoka worrisome or high-risk features were excluded. Two radiologists reviewed all images. Cyst size was recorded at the initial and final imaging studies and growth rate was calculated. We collected patient demographic data, cyst characteristics, and clinical outcomes; univariate logistic regression models were used to determine the odds of developing worrisome features. The primary outcomes were to determine growth rate of low-risk BD-IPMNs and to assess whether cyst growth rate correlates high-risk features of IPMNs. Based on image analyses, cysts were initially a median 11 mm (range, 3-31 mm) and their final size was 12.5 mm (range, 3-42 mm). After a median follow-up time of 56 months (range, 12-163 months), the median cyst growth rate was 0.29 mm/year. Twelve patients developed worrisome features, no patients developed high-risk features, 4 patients had surgical resection, and no cancers developed. The rate of BD-IPMN growth was greater in patients who developed worrisome features than those who did not (2.84 mm/year vs 0.23 mm/year; P < .001). The odds of developing worrisome features increased for each unit (mm) increase in cyst size (odds ratio, 1.149; 95% CI, 1.035-1.276, P = .009). In a retrospective analysis of images from patients with BD-IPMN, we found low-risk BD-IPMNs to grow at an extremely low rate (less than 0.3 mm/year). BD-IPMNs in only about 6% of patients developed worrisome features, and none developed high-risk features or invasive cancers. BD-IPMNs that developed worrisome features were associated with a significantly higher rate of growth than lesions with low-risk features. Low risk BD-IPMNs that grow more than 2.5 mm/year might require surveillance. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

PubMed

Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas; Compta, Yaroslau; Englund, Elisabet; Ferguson, Leslie W; Gelpi, Ellen; Giese, Armin; Irwin, David J; Meissner, Wassilios G; Nilsson, Christer; Pantelyat, Alexander; Rajput, Alex; van Swieten, John C; Troakes, Claire; Josephs, Keith A; Lang, Anthony E; Mollenhauer, Brit; Müller, Ulrich; Whitwell, Jennifer L; Antonini, Angelo; Bhatia, Kailash P; Bordelon, Yvette; Corvol, Jean-Christophe; Colosimo, Carlo; Dodel, Richard; Grossman, Murray; Kassubek, Jan; Krismer, Florian; Levin, Johannes; Lorenzl, Stefan; Morris, Huw; Nestor, Peter; Oertel, Wolfgang H; Rabinovici, Gil D; Rowe, James B; van Eimeren, Thilo; Wenning, Gregor K; Boxer, Adam; Golbe, Lawrence I; Litvan, Irene; Stamelou, Maria; Höglinger, Günter U

2017-07-01

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

A comparison of clinical features of coronary artery spasm with and without thyrotoxicosis.

PubMed

Lee, Soo Youn; Yu, Cheol Woong; Choi, Young Jin; Choi, Rak Kyeong; Park, Jin Sik; Lee, Hyun Jong; Kim, Je Sang; Jang, Ho Jun; Jang, Duck Hyun; Chae, Myung Joon; Shim, Won Heum; Ro, Young Moo

2014-03-01

Several reports have suggested that thyrotoxicosis may induce severe coronary artery spasm (CAS). However, there are few data regarding the differences in clinical characteristics of CAS with and without thyrotoxicosis. The aim of our study is to compare the clinical features of CAS with and without thyrotoxicosis. We evaluated 430 consecutive patients with CAS [patients with thyrotoxicosis (N=32, group I) and those without (N=398, group II)] at a single institute between January 2001 and June 2011. We compared clinical presentations, angiographic findings, and adverse outcomes (a composite outcome of cardiac death, myocardial infarction, or rehospitalization due to cardiac cause) of both groups. There was higher incidence of acute myocardial infarction at initial presentation in group I (15.6 vs. 5.8%, P=0.04). CAS with thyrotoxicosis was more diffuse (59.4 vs. 39.3%, P=0.03), more medically intractable (9.4 vs. 0%, P=0.001), and more frequently involved the left main vessel (25.0 vs.0.8%, P=0.001) than CAS without thyrotoxicosis. During the follow-up period (median 43 months), there were no significant differences between the two groups in terms of the risk of adverse outcomes (hazard ratio for CAS with thyrotoxicosis, 1.029; 95% confidence interval, 0.347-3.054). Clinical and angiographic presentations of CAS with thyrotoxicosis were more severe than CAS without thyrotoxicosis, but clinical outcomes were similar in both groups. Optimal vasodilator therapy is essential for the management of CAS with thyrotoxicosis. Thyroid function test should be mandatory for all patients with CAS.

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents.

PubMed

Leigh, Margaret W; Ferkol, Thomas W; Davis, Stephanie D; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D; Sagel, Scott D; Milla, Carlos; Olivier, Kenneth N; Sullivan, Kelli M; Zariwala, Maimoona A; Pittman, Jessica E; Shapiro, Adam J; Carson, Johnny L; Krischer, Jeffrey; Hazucha, Milan J; Knowles, Michael R

2016-08-01

Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0-18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as "definite PCD" (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), "probable/possible PCD" (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and "other diagnosis or undefined." Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. From 534 participants 18 years of age and younger, 205 were identified as having "definite PCD" (including 164 with two mutations in a PCD-associated gene), 187 were categorized as "other diagnosis or undefined," and 142 were defined as having "probable/possible PCD." Participants with "definite PCD" were compared with the "other diagnosis or undefined" group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167).

Inverse optimization of objective function weights for treatment planning using clinical dose-volume histograms

NASA Astrophysics Data System (ADS)

Babier, Aaron; Boutilier, Justin J.; Sharpe, Michael B.; McNiven, Andrea L.; Chan, Timothy C. Y.

2018-05-01

We developed and evaluated a novel inverse optimization (IO) model to estimate objective function weights from clinical dose-volume histograms (DVHs). These weights were used to solve a treatment planning problem to generate ‘inverse plans’ that had similar DVHs to the original clinical DVHs. Our methodology was applied to 217 clinical head and neck cancer treatment plans that were previously delivered at Princess Margaret Cancer Centre in Canada. Inverse plan DVHs were compared to the clinical DVHs using objective function values, dose-volume differences, and frequency of clinical planning criteria satisfaction. Median differences between the clinical and inverse DVHs were within 1.1 Gy. For most structures, the difference in clinical planning criteria satisfaction between the clinical and inverse plans was at most 1.4%. For structures where the two plans differed by more than 1.4% in planning criteria satisfaction, the difference in average criterion violation was less than 0.5 Gy. Overall, the inverse plans were very similar to the clinical plans. Compared with a previous inverse optimization method from the literature, our new inverse plans typically satisfied the same or more clinical criteria, and had consistently lower fluence heterogeneity. Overall, this paper demonstrates that DVHs, which are essentially summary statistics, provide sufficient information to estimate objective function weights that result in high quality treatment plans. However, as with any summary statistic that compresses three-dimensional dose information, care must be taken to avoid generating plans with undesirable features such as hotspots; our computational results suggest that such undesirable spatial features were uncommon. Our IO-based approach can be integrated into the current clinical planning paradigm to better initialize the planning process and improve planning efficiency. It could also be embedded in a knowledge-based planning or adaptive radiation therapy framework to automatically generate a new plan given a predicted or updated target DVH, respectively.

Inverse optimization of objective function weights for treatment planning using clinical dose-volume histograms.

PubMed

Babier, Aaron; Boutilier, Justin J; Sharpe, Michael B; McNiven, Andrea L; Chan, Timothy C Y

2018-05-10

We developed and evaluated a novel inverse optimization (IO) model to estimate objective function weights from clinical dose-volume histograms (DVHs). These weights were used to solve a treatment planning problem to generate 'inverse plans' that had similar DVHs to the original clinical DVHs. Our methodology was applied to 217 clinical head and neck cancer treatment plans that were previously delivered at Princess Margaret Cancer Centre in Canada. Inverse plan DVHs were compared to the clinical DVHs using objective function values, dose-volume differences, and frequency of clinical planning criteria satisfaction. Median differences between the clinical and inverse DVHs were within 1.1 Gy. For most structures, the difference in clinical planning criteria satisfaction between the clinical and inverse plans was at most 1.4%. For structures where the two plans differed by more than 1.4% in planning criteria satisfaction, the difference in average criterion violation was less than 0.5 Gy. Overall, the inverse plans were very similar to the clinical plans. Compared with a previous inverse optimization method from the literature, our new inverse plans typically satisfied the same or more clinical criteria, and had consistently lower fluence heterogeneity. Overall, this paper demonstrates that DVHs, which are essentially summary statistics, provide sufficient information to estimate objective function weights that result in high quality treatment plans. However, as with any summary statistic that compresses three-dimensional dose information, care must be taken to avoid generating plans with undesirable features such as hotspots; our computational results suggest that such undesirable spatial features were uncommon. Our IO-based approach can be integrated into the current clinical planning paradigm to better initialize the planning process and improve planning efficiency. It could also be embedded in a knowledge-based planning or adaptive radiation therapy framework to automatically generate a new plan given a predicted or updated target DVH, respectively.

Age dependence of clinical and pathological manifestations of autoimmune demyelination. Implications for multiple sclerosis.

PubMed

Smith, M E; Eller, N L; McFarland, H F; Racke, M K; Raine, C S

1999-10-01

A prominent feature of the clinical spectrum of multiple sclerosis (MS) is its high incidence of onset in the third decade of life and the relative rarity of clinical manifestations during childhood and adolescence, features suggestive of age-related restriction of clinical expression. Experimental allergic encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune demyelination with many similarities to MS, has a uniform rapid onset and a high incidence of clinical and pathological disease in adult (mature) animals. Like MS, EAE is most commonly seen and studied in female adults. In this study, age-related resistance to clinical EAE has been examined with the adoptive transfer model of EAE in SJL mice that received myelin basic protein-sensitized cells from animals 10 days (sucklings) to 12 weeks (young adults) of age. A variable delay before expression of clinical EAE was observed between the different age groups. The preclinical period was longest in the younger (<14 days of age) animals, and shortest in animals 6 to 8 weeks old at time of transfer. Young animals initially resistant to EAE eventually expressed well-developed clinical signs by 6 to 7 weeks of age. This was followed by a remitting, relapsing clinical course. For each age at time of sensitization, increased susceptibility of females compared to males was observed. Examination of the CNS of younger animal groups during the preclinical period showed lesions of acute EAE. Older age groups developed onset of signs coincident with acute CNS lesions. This age-related resistance to clinical EAE in developing mice is reminiscent of an age-related characteristic of MS previously difficult to study in vivo. The associated subclinical CNS pathology and age-related immune functions found in young animals may be relevant to the increasing clinical expression of MS with maturation, and may allow study of factors associated with the known occasional poor correlation of CNS inflammation and demyelination and clinical changes in this disease.

Corticobasal degeneration.

PubMed

Stover, N P; Watts, R L

2001-01-01

Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative disease with both motor and cognitive dysfunction. The diagnosis is probably underestimated because of the heterogeneity of clinical features, overlap with symptoms, and pathologic findings of other neurodegenerative diseases. The most characteristic initial motor symptoms are akinesia, rigidity, and apraxia. Dystonia and alien limb phenomena are frequently observed. There is often a parkinsonian picture with failure or lack of efficacy of dopaminergic medical therapy. Cognitive decline, prompting the diagnosis of dementia, may be the most common presentation of CBD that is misdiagnosed. Pathology is characterized by an asymmetric frontoparietal neuronal loss and gliosis with ballooned, achromatic cortical neurons, nigral degeneration, and variable subcortical involvement. Neuroimaging and electrophysiologic studies may help with the diagnosis but are not specific. Treatment is primarily symptomatic and minimally effective, especially after the first several years of symptoms. CBD should be considered in the differential diagnosis of patients with motor and cognitive dysfunction presenting with cortical and subcortical features. Further studies to elucidate molecular abnormalities and biological markers associated with CBD are needed to improve clinical diagnosis and treatment of patients with this disorder.

11p15 duplication and 13q34 deletion with Beckwith-Wiedemann syndrome and factor VII deficiency.

PubMed

Jurkiewicz, Dorota; Kugaudo, Monika; Tańska, Anna; Wawrzkiewicz-Witkowska, Angelika; Tomaszewska, Agnieszka; Kucharczyk, Marzena; Cieślikowska, Agata; Ciara, Elżbieta; Krajewska-Walasek, Małgorzata

2015-06-01

Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith-Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation-sensitive multiplex ligation-dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay. © 2015 Japan Pediatric Society.

Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates.

PubMed

Reisler, Ronald B; Yu, Chenggang; Donofrio, Michael J; Warren, Travis K; Wells, Jay B; Stuthman, Kelly S; Garza, Nicole L; Vantongeren, Sean A; Donnelly, Ginger C; Kane, Christopher D; Kortepeter, Mark G; Bavari, Sina; Cardile, Anthony P

2017-08-01

The Ebola virus (EBOV) outbreak in West Africa during 2013-2016 demonstrated the need to improve Ebola virus disease (EVD) diagnostics and standards of care. This retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal EVD to assess associations with improved survival time. In addition, the study identified laboratory values useful as predictors of survival, surrogates for EBOV viral loads, and triggers for initiation of therapeutic interventions in these nonhuman primate models. Furthermore, the data support that, in nonhuman primates, the Makona strain of EBOV may be less virulent than the Kikwit strain of EBOV. The applicability of these findings as potential diagnostic and management tools for EVD in humans warrants further investigation.

Management of a case of Candida albicans endogenous endophthalmitis with intravitreal caspofungin

PubMed Central

Yadav, Harshali Manish; Thomas, Boben; Thampy, Cherian; Panaknti, Tandava Krishnan

2017-01-01

We report a case of Candida albicans endogenous endophthalmitis treated with intravitreal caspofungin. The patient was a known case of acute lymphoblastic leukemia on chemotherapy and presented to us with features suggestive of endogenous endophthalmitis. He was treated initially with intravenous (IV) caspofungin and intravitreal amphotericin B. Patients condition worsened after IV caspofungin was replaced by amphotericin B necessitating a core vitrectomy. The patient was given the option of off-label caspofungin intravitreal injection for which the patient consented. There was a gradual improvement in the clinical picture. The situation worsened after the injections were stopped necessitating a revitrectomy. The study demonstrates the clinical efficacy of intravitreal caspofungin for the first time in human eyes. PMID:28643723

Intracranial EEG fluctuates over months after implanting electrodes in human brain

NASA Astrophysics Data System (ADS)

Ung, Hoameng; Baldassano, Steven N.; Bink, Hank; Krieger, Abba M.; Williams, Shawniqua; Vitale, Flavia; Wu, Chengyuan; Freestone, Dean; Nurse, Ewan; Leyde, Kent; Davis, Kathryn A.; Cook, Mark; Litt, Brian

2017-10-01

Objective. Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings. Approach. Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for the duration of each patient’s recording. Metrics to capture post-implantation feature changes and inflexion points were computed on group and individual levels. A linear mixed model was used to characterize transient group-level changes in feature values post-implantation and independent linear models were used to describe individual variability. Main results. A significant decline in features important to seizure detection and prediction algorithms (mean line length, energy, and half-wave), as well as mean power in the Berger and high gamma bands, was observed in many patients over 100 d following implantation. In addition, spatial variability across electrodes declines post-implantation following a similar timeframe. All selected features decreased by 14-50% in the initial 75 d of recording on the group level, and at least one feature demonstrated this pattern in 13 of the 15 patients. Our findings indicate that iEEG signal features demonstrate increased variability following implantation, most notably in the weeks immediately post-implant. Significance. These findings suggest that conclusions drawn from iEEG, both clinically and for research, should account for spatiotemporal signal variability and that properly assessing the iEEG in patients, depending upon the application, may require extended monitoring.

Primary perivascular epithelioid cell tumors of the liver: CT/MRI findings and clinical outcomes.

PubMed

O'Malley, Martin E; Chawla, Tanya P; Lavelle, Lisa P; Cleary, Sean; Fischer, Sandra

2017-06-01

The purpose of our study was to describe the CT and MRI features of primary PEComas of the liver and to document the associated clinical outcomes. Retrospective study included 20 patients with primary hepatic perivascular epithelioid cell tumors (PEComa) with pathology and clinical outcomes for correlation. Study group included 20 patients: 16 women, 4 men; mean age 53 (range 35-77) years. Initial pathology diagnoses were classic angiomyolipoma (AML) (n = 11), epithelioid AML (n = 7), and PEComa not otherwise specified (n = 2). Mean tumor size was 5.1 (range 1.3-15.0) cm. CT/MRI features included well-defined margins 20/20 (100%), arterial enhancement 18/19 (95%), subcapsular location 17/20 (85%), heterogeneous 16/20 (80%), dysmorphic vessels 14/20 (70%), fat 13/20 (65%), hemorrhage 4/20 (20%), cystic components 4/20 (20%), and calcification 1/20 (5%). At the time of discovery, 18 patients were asymptomatic and their tumors were incidentally detected on imaging, and 2 patients were symptomatic. Ultimately, 18 tumors were benign and 2 developed metastases. On CT/MRI, most primary hepatic PEComas were well-defined, arterial enhancing, subcapsular, heterogeneous masses that often had dysmorphic vessels and contained fat. Most tumors were benign but complications included local symptoms, bleeding, and malignant change.

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome.

PubMed

Sproule, Douglas M; Kaufmann, Petra

2008-10-01

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.

Severe Propanil [N-(3,4-dichlorophenyl) propanamide] Pesticide Self-Poisoning

PubMed Central

Eddleston, Michael; Rajapakshe, Manjula; Roberts, Darren; Reginald, K; Sheriff, M H Rezvi; Dissanayake, Wasantha; Buckley, Nick

2007-01-01

Background propanil pesticide poisoning can produce methaemoglobinaemia, tissue hypoxia, and depression of CNS and respiratory system. It has been recorded only rarely worldwide and most current poison texts consider propanil to be of low toxicity. However, propanil self-poisoning is a significant clinical problem in parts of Sri Lanka and a not uncommon cause of death. Aim of study to report the clinical features and management of severe propanil poisoning. Patients and Methods we report a retrospective case series of patients who were treated in the intensive care unit (ICU) of and/or died in Anuradhapura General Hospital between 1998 and early 2002. Results sixteen patients were identified. Common manifestations of toxicity included confusion, reduced conscious level, cyanosis, and respiratory depression. Marked haemolysis was noted in several patients. Nine deaths occurred due to respiratory depression and cardiorespiratory arrest. Management was difficult given the lack of IV methylene blue, inability to measure methaemoglobin levels, and paucity of ICU beds. Conclusions this series indicates that propanil poisoning can be a severe form of self-poisoning, particularly in resource-poor settings. We have now initiated the establishment of a prospective series of propanil poisoned patients to further describe its clinical features, responsiveness to therapy, and case fatality rate. PMID:12507053

Guillain-Barré Syndrome presenting as unilateral hip pain in a child.

PubMed

Neocleous, Charalambos; Diakolios, Konstandinos; Adramerina, Alkistis; Varveris, Evangelos; Tsioni, Vasiliki; Machairidou, Konstandina

2015-01-01

The aim of this report is to highlight the importance of close observation and follow-up in children who present with an acutely irritable hip. This is because hip pain is a symptom of not only benign but also severe conditions. Thus, at the time of the initial presentation, hip pain can be misdiagnosed. This report serves as an example for a wide range of doctors such as orthopaedic surgeons, paediatricians, emergency room physicians or primary care physicians, because these are the first-line doctors who treat patients with a painful hip. We herein present a three-year-old child who was admitted to our hospital with pain in the right leg and initially diagnosed with transient synovitis of the hip. An additional examination two days later, after severe deterioration of the clinical picture, revealed that our patient was actually suffering from Guillain-Barré syndrome. Failure to diagnose Guillain-Barré syndrome and initiating prompt treatment is potentially life-threatening. Clinicians should be aware that hip pain could be the presenting complaint of Guillain-Barré syndrome, a syndrome that has many clinical features. Even when all the clinical and laboratory findings indicate a benign condition, Guillain- Barré syndrome should still be considered. Therefore, close observation and follow-up in children who present with an acutely irritable hip is highly recommended. In this way, the potentially catastrophic consequences of more severe conditions can be avoided. Copyright © 2015 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease.

PubMed

Satlin, Andrew; Wang, Jinping; Logovinsky, Veronika; Berry, Scott; Swanson, Chad; Dhadda, Shobha; Berry, Donald A

2016-01-01

Recent failures in phase 3 clinical trials in Alzheimer's disease (AD) suggest that novel approaches to drug development are urgently needed. Phase 3 risk can be mitigated by ensuring that clinical efficacy is established before initiating confirmatory trials, but traditional phase 2 trials in AD can be lengthy and costly. We designed a Bayesian adaptive phase 2, proof-of-concept trial with a clinical endpoint to evaluate BAN2401, a monoclonal antibody targeting amyloid protofibrils. The study design used dose response and longitudinal modeling. Simulations were used to refine study design features to achieve optimal operating characteristics. The study design includes five active treatment arms plus placebo, a clinical outcome, 12-month primary endpoint, and a maximum sample size of 800. The average overall probability of success is ≥80% when at least one dose shows a treatment effect that would be considered clinically meaningful. Using frequent interim analyses, the randomization ratios are adapted based on the clinical endpoint, and the trial can be stopped for success or futility before full enrollment. Bayesian statistics can enhance the efficiency of analyzing the study data. The adaptive randomization generates more data on doses that appear to be more efficacious, which can improve dose selection for phase 3. The interim analyses permit stopping as soon as a predefined signal is detected, which can accelerate decision making. Both features can reduce the size and duration of the trial. This study design can mitigate some of the risks associated with advancing to phase 3 in the absence of data demonstrating clinical efficacy. Limitations to the approach are discussed.

Persistence of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort: a prospective two‐year follow‐up

PubMed Central

Calkins, Monica E.; Moore, Tyler M.; Satterthwaite, Theodore D.; Wolf, Daniel H.; Turetsky, Bruce I.; Roalf, David R.; Merikangas, Kathleen R.; Ruparel, Kosha; Kohler, Christian G.; Gur, Ruben C.; Gur, Raquel E.

2017-01-01

Prospective evaluation of youths with early psychotic‐like experiences can enrich our knowledge of clinical, biobehavioral and environmental risk and protective factors associated with the development of psychotic disorders. We aimed to investigate the predictors of persistence or worsening of psychosis spectrum features among US youth through the first large systematic study to evaluate subclinical symptoms in the community. Based on Time 1 screen of 9,498 youth (age 8‐21) from the Philadelphia Neurodevelopmental Cohort, a subsample of participants was enrolled based on the presence (N=249) or absence (N=254) of baseline psychosis spectrum symptoms, prior participation in neuroimaging, and current neuroimaging eligibility. They were invited to participate in a Time 2 assessment two years on average following Time 1. Participants were administered the Structured Interview for Prodromal Syndromes, conducted blind to initial screen status, along with the Schizotypal Personality Questionnaire and other clinical measures, computerized neurocognitive testing, and neuroimaging. Clinical and demographic predictors of symptom persistence were examined using logistic regression. At Time 2, psychosis spectrum features persisted or worsened in 51.4% of youths. Symptom persistence was predicted by higher severity of subclinical psychosis, lower global functioning, and prior psychiatric medication at baseline. Youths classified as having psychosis spectrum symptoms at baseline but not at follow‐up nonetheless exhibited comparatively higher symptom levels and lower functioning at both baseline and follow‐up than typically developing youths. In addition, psychosis spectrum features emerged in a small number of young people who previously had not reported significant symptoms but who had exhibited early clinical warning signs. Together, our findings indicate that varying courses of psychosis spectrum symptoms are evident early in US youth, supporting the importance of investigating psychosis risk as a dynamic developmental process. Neurocognition, brain structure and function, and genomics may be integrated with clinical data to provide early indices of symptom persistence and worsening in youths at risk for psychosis. PMID:28127907

Magnetization-prepared rapid acquisition with gradient echo magnetic resonance imaging signal and texture features for the prediction of mild cognitive impairment to Alzheimer’s disease progression

PubMed Central

Martinez-Torteya, Antonio; Rodriguez-Rojas, Juan; Celaya-Padilla, José M.; Galván-Tejada, Jorge I.; Treviño, Victor; Tamez-Peña, Jose

2014-01-01

Abstract. Early diagnoses of Alzheimer’s disease (AD) would confer many benefits. Several biomarkers have been proposed to achieve such a task, where features extracted from magnetic resonance imaging (MRI) have played an important role. However, studies have focused exclusively on morphological characteristics. This study aims to determine whether features relating to the signal and texture of the image could predict mild cognitive impairment (MCI) to AD progression. Clinical, biological, and positron emission tomography information and MRI images of 62 subjects from the AD neuroimaging initiative were used in this study, extracting 4150 features from each MRI. Within this multimodal database, a feature selection algorithm was used to obtain an accurate and small logistic regression model, generated by a methodology that yielded a mean blind test accuracy of 0.79. This model included six features, five of them obtained from the MRI images, and one obtained from genotyping. A risk analysis divided the subjects into low-risk and high-risk groups according to a prognostic index. The groups were statistically different (p-value=2.04e−11). These results demonstrated that MRI features related to both signal and texture add MCI to AD predictive power, and supported the ongoing notion that multimodal biomarkers outperform single-modality ones. PMID:26158047

MRI signal and texture features for the prediction of MCI to Alzheimer's disease progression

NASA Astrophysics Data System (ADS)

Martínez-Torteya, Antonio; Rodríguez-Rojas, Juan; Celaya-Padilla, José M.; Galván-Tejada, Jorge I.; Treviño, Victor; Tamez-Peña, José G.

2014-03-01

An early diagnosis of Alzheimer's disease (AD) confers many benefits. Several biomarkers from different information modalities have been proposed for the prediction of MCI to AD progression, where features extracted from MRI have played an important role. However, studies have focused almost exclusively in the morphological characteristics of the images. This study aims to determine whether features relating to the signal and texture of the image could add predictive power. Baseline clinical, biological and PET information, and MP-RAGE images for 62 subjects from the Alzheimer's Disease Neuroimaging Initiative were used in this study. Images were divided into 83 regions and 50 features were extracted from each one of these. A multimodal database was constructed, and a feature selection algorithm was used to obtain an accurate and small logistic regression model, which achieved a cross-validation accuracy of 0.96. These model included six features, five of them obtained from the MP-RAGE image, and one obtained from genotyping. A risk analysis divided the subjects into low-risk and high-risk groups according to a prognostic index, showing that both groups are statistically different (p-value of 2.04e-11). The results demonstrate that MRI features related to both signal and texture, add MCI to AD predictive power, and support the idea that multimodal biomarkers outperform single-modality biomarkers.

Evaluation of a web based informatics system with data mining tools for predicting outcomes with quantitative imaging features in stroke rehabilitation clinical trials

NASA Astrophysics Data System (ADS)

Wang, Ximing; Kim, Bokkyu; Park, Ji Hoon; Wang, Erik; Forsyth, Sydney; Lim, Cody; Ravi, Ragini; Karibyan, Sarkis; Sanchez, Alexander; Liu, Brent

2017-03-01

Quantitative imaging biomarkers are used widely in clinical trials for tracking and evaluation of medical interventions. Previously, we have presented a web based informatics system utilizing quantitative imaging features for predicting outcomes in stroke rehabilitation clinical trials. The system integrates imaging features extraction tools and a web-based statistical analysis tool. The tools include a generalized linear mixed model(GLMM) that can investigate potential significance and correlation based on features extracted from clinical data and quantitative biomarkers. The imaging features extraction tools allow the user to collect imaging features and the GLMM module allows the user to select clinical data and imaging features such as stroke lesion characteristics from the database as regressors and regressands. This paper discusses the application scenario and evaluation results of the system in a stroke rehabilitation clinical trial. The system was utilized to manage clinical data and extract imaging biomarkers including stroke lesion volume, location and ventricle/brain ratio. The GLMM module was validated and the efficiency of data analysis was also evaluated.

[The Outpatient Clinic for Adolescent Risk-taking and Self-harm behaviors (AtR!Sk) - A Pioneering Approach of Outpatient Early Detection and Intervention of Borderline Personality Disorder].

PubMed

Kaess, Michael; Ghinea, Denisa; Fischer-Waldschmidt, Gloria; Resch, Franz

2017-07-01

The Outpatient Clinic for Adolescent Risk-taking and Self-harm behaviors (AtR!Sk) - A Pioneering Approach of Outpatient Early Detection and Intervention of Borderline Personality Disorder Self-harm and risk-taking behaviors are frequently occurring problems in adolescents' everyday life and commonly challenge the present child and adolescent health-care system. Those behaviors are typical features of borderline-personality disorder (BPD), a severe mental disorder that is associated with immense psychological strain, increased risk of mortality and poor psychosocial functioning. Despite controversy in the past, recent evidence shows that BPD is a valid and reliable diagnosis in adolescence. Consequently, specified and effective intervention programs for this age group are necessary. Instead, present health-care services for children and adolescents in Germany are usually characterized by long waiting periods for specialized outpatient treatments and unnecessary expanses of unnecessary long inpatient stays. Alternatively, and in order to prevent serious long-term consequences, new concepts - integrated in an ambulatory setting and close to patients' daily routines - should focus on early detection and treatment of adolescents at-risk presenting with borderline personality features. The specialist outpatient clinic AtR!Sk at the University Hospital Heidelberg ensures a low-threshold initial contact service, comprehensive and accurate diagnosis of BPD features, and rapidly "tailored" therapy for young people presenting with any types of risk-taking and self-harm behavior. AtR!Sk - as a pioneering approach in south Germany - provides evidence-based early detection and intervention for adolescent BPD.

Sinonasal organized hematoma: Clinical features of seventeen cases and a systematic review.

PubMed

Choi, Soo Jung; Seo, Sung Tae; Rha, Ki-Sang; Kim, Yong Min

2015-09-01

Organized hematoma (OH) is a rare non-neoplastic disease. We studied the clinical characteristics of 17 patients with sinonasal OH and those of 75 cases in the English literature. Retrospective review of medical records and systematic review of the literature on OH. Comprehensive review of the English-language literature on OH was performed. We screened all eligible cases based on initial features, and 75 eligible cases found in 15 publications were analyzed. We also retrospectively analyzed and compared medical records of 17 patients diagnosed with pathologically proven sinonasal OH. Data such as demographics, clinical characteristics, pathologic features, radiologic findings, treatment modalities, and follow-up results were compared to the 75 previously mentioned cases. Fifteen cases involved the maxillary sinus, one case involved the frontal sinus, and one case involved the sphenoid sinus. There were six patients over 60 years old, and all were taking an antiplatelet agent. The paranasal sinus computed tomography (CT) of seven patients showed bony destruction of the involved sinus. A review of the available literature revealed mostly similar results with our cases, except for the proportion of patients taking aspirin (5.3%) and sex distribution (male:female = 49:25). We reported 17 cases of OH, including a case of frontal sinus and a case of sphenoid sinus lesion. A large proportion of OH patients had bony destruction of the affected sinus on CT. In these patients, a careful diagnosis should be made to distinguish them from a malignant tumor or other expansile diseases. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Comparative study of the clinical presentation of Legionella pneumonia and other community-acquired pneumonias.

PubMed

Sopena, N; Sabrià-Leal, M; Pedro-Botet, M L; Padilla, E; Dominguez, J; Morera, J; Tudela, P

1998-05-01

The aim of this study was to compare the clinical, biological, and radiologic features of presentation in the emergency ward of community-acquired pneumonia (CAP) by Legionella pneumophila (LP) and other community-acquired bacterial pneumonias to help in early diagnosis of CAP by LP. Three hundred ninety-two patients with CAP were studied prospectively in the emergency department of a 600-bed university hospital. Univariate and multivariate analyses were performed to compare epidemiologic and demographic data and clinical, analytical, and radiologic features of presentation in 48 patients with CAP by LP and 125 patients with CAP by other bacterial etiology (68 by Streptococcus pneumoniae, 41 by Chlamydia pneumoniae, 5 by Mycoplasma pneumoniae, 4 by Coxiella burnetii, 3 by Pseudomonas aeruginosa, 2 by Haemophilus influenzae, and 2 by Nocardia species. Univariate analysis showed that CAP by LP was more frequent in middle-aged, male healthy (but alcohol drinking) patients than CAP by other etiology. Moreover, the lack of response to previous beta-lactamic drugs, headache, diarrhea, severe hyponatremia, and elevation in serum creatine kinase (CK) levels on presentation were more frequent in CAP by LP, while cough, expectoration, and thoracic pain were more frequent in CAP by other bacterial etiology. However, multivariate analysis only confirmed these differences with respect to lack of underlying disease, diarrhea, and elevation in the CK level. We conclude that detailed analysis of features of presentation of CAP allows suspicion of Legionnaire's disease in the emergency department. The initiation of antibiotic treatment, including a macrolide, and the performance of rapid diagnostic techniques are mandatory in these cases.

Dynamic skin changes of acute radiation dermatitis revealed by in vivo reflectance confocal microscopy.

PubMed

Vano-Galvan, S; Fernandez-Lizarbe, E; Truchuelo, M; Diaz-Ley, B; Grillo, E; Sanchez, V; Ríos-Buceta, L; Paoli, J; Sancho, S; Montero, A; Hernanz, R; Ramos, A; Jaen, P; Gonzalez, S

2013-09-01

A better knowledge of the dynamic biological changes that the skin undergoes in response to ionizing radiation is advisable to improve the management of radiation dermatitis, allowing selection of patients needing treatment or close monitoring. To describe the evolution of the skin in response to ionizing radiation through the reflectance confocal microscopy (RCM) features of acute radiation dermatitis. In this prospective descriptive study, six women (median age, 55 years; range, 45-80 years) diagnosed with breast cancer in stages IA-IB undergoing adjuvant radiotherapy were included in the study through consecutive sampling. Clinical, dermoscopic and RCM evaluation of the skin were performed prior to treatment and on days 1, 15, 30 and 45 after radiotherapy. While clinical features of radiation dermatitis emerged after 30 days on average, histopathological changes were detectable by RCM after a mean time of 15 days. The main RCM features included initial appearance of spongiosis, exocytosis and inflammatory cells followed by the presence of dendritic-shaped cells, 'streaming-like figures', 'broken geographic papillae', epidermal architectural disarray, effacement of rete ridges, melanophages and, finally, hyperpigmentation of the basal layer. RCM may safely detect the dynamic biological changes that the skin undergoes in response to ionizing radiation, even before than clinical onset of acute radiation dermatitis. Therefore, RCM may be useful to make an early and non-invasive diagnosis of radiation dermatitis during radiotherapy, allowing an early selection of patients needing treatment or close monitoring and avoiding skin biopsies. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Clinical characteristics of acute encephalopathy with acute brain swelling: A peculiar type of acute encephalopathy.

PubMed

Nukui, Megumi; Kawawaki, Hisashi; Inoue, Takeshi; Kuki, Ichiro; Okazaki, Shin; Amo, Kiyoko; Togawa, Masao; Ishikawa, Junichi; Rinka, Hiroshi; Shiomi, Masashi

2018-06-07

Acute encephalopathy has been observed with acute brain swelling (ABS) that is characterized by rapid progression to whole-brain swelling. The objective of this study was to describe the clinical characteristics of ABS. We encountered four patients with ABS and retrospectively investigated their clinical data with a medical chart review. Three patients had seizure clustering or status epilepticus in the clinical course. Signs of elevated intracranial pressure (ICP) appeared 3-9 h after the first convulsive attack in three patients. In all patients, signs of brainstem involvement appeared 1-8 h after signs of elevated ICP. Mild hyponatremia that progressed after signs of elevated ICP appeared was noted in three patients. Brain CT revealed mild brain swelling in the initial phase, which rapidly progressed to whole-brain swelling. No focal abnormalities were detected on brain MRI in one patient. Continuous electroencephalography was initially normal, but in two patients, high-amplitude slow waves appeared with rapid changes before signs of brainstem involvement. Although recovery was achieved without sequelae in two patients, outcome was fatal for the other two. The pathogenesis of ABS has yet to be clarified, but clinical features in our patients are not consistent with any established subtypes of acute encephalopathy. Therefore, we believe that ABS should be recognized as a new type of acute encephalopathy. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Bladder cancer treatment response assessment with radiomic, clinical, and radiologist semantic features

NASA Astrophysics Data System (ADS)

Gordon, Marshall N.; Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2018-02-01

We are developing a decision support system for assisting clinicians in assessment of response to neoadjuvant chemotherapy for bladder cancer. Accurate treatment response assessment is crucial for identifying responders and improving quality of life for non-responders. An objective machine learning decision support system may help reduce variability and inaccuracy in treatment response assessment. We developed a predictive model to assess the likelihood that a patient will respond based on image and clinical features. With IRB approval, we retrospectively collected a data set of pre- and post- treatment CT scans along with clinical information from surgical pathology from 98 patients. A linear discriminant analysis (LDA) classifier was used to predict the likelihood that a patient would respond to treatment based on radiomic features extracted from CT urography (CTU), a radiologist's semantic feature, and a clinical feature extracted from surgical and pathology reports. The classification accuracy was evaluated using the area under the ROC curve (AUC) with a leave-one-case-out cross validation. The classification accuracy was compared for the systems based on radiomic features, clinical feature, and radiologist's semantic feature. For the system based on only radiomic features the AUC was 0.75. With the addition of clinical information from examination under anesthesia (EUA) the AUC was improved to 0.78. Our study demonstrated the potential of designing a decision support system to assist in treatment response assessment. The combination of clinical features, radiologist semantic features and CTU radiomic features improved the performance of the classifier and the accuracy of treatment response assessment.

Characteristics of Clinical Studies Conducted Over the Total Product Life Cycle of High-Risk Therapeutic Medical Devices Receiving FDA Premarket Approval in 2010 and 2011.

PubMed

Rathi, Vinay K; Krumholz, Harlan M; Masoudi, Frederick A; Ross, Joseph S

2015-08-11

The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle. To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014. Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator-initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer/investigator-initiated postmarket studies, respectively. Approximately half of all studies used no comparator (pivotal: 13/30 [43.3%]; completed postmarket: 16/26 [61.5%]; ongoing postmarket: 70/153 [45.8%]). Median duration of primary effectiveness end point follow-up was 3.0 months (IQR, 3.0-12.0), 9.0 months (IQR, 0.3-12.0), and 12.0 months (IQR, 7.0-24.0) for pivotal, completed postmarket, and ongoing postmarket studies, respectively. Among high-risk therapeutic devices approved via the FDA PMA pathway, total product life cycle evidence generation varied in both the number and quality of premarket and postmarket studies, with approximately 13% of initiated postmarket studies completed between 3 and 5 years after FDA approval.

SAPHO: What radiologists should know.

PubMed

Depasquale, R; Kumar, N; Lalam, R K; Tins, B J; Tyrrell, P N M; Singh, J; Cassar-Pullicino, V N

2012-03-01

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) is an umbrella acronym for inflammatory clinical conditions whose common denominator is aseptic osteoarticular involvement with characteristic skin lesions. It involves all ages, can involve any skeletal site, and has variable imaging appearances depending on the stage/age of the lesion and imaging method. It mimics important differentials including infection and neoplasia. Awareness of the imaging features, especially in the spine, facilitates early diagnosis, prevents repeated biopsies, and avoids unnecessary surgery, while initiating appropriate treatment. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Shwachman-Bodian-Diamond syndrome: metaphyseal chondrodysplasia in children with pancreatic insufficiency and neutropenia.

PubMed

Levin, Terry L; Mäkitie, Outi; Berdon, Walter E; Lachman, Ralph S

2015-07-01

Shwachman-Bodian-Diamond syndrome (OMIM 260400) was identified in 1964 by pediatricians Harry Shwachman, a leader in cystic fibrosis, and Louis K. Diamond, a hematologist, along with pediatrician and morbid anatomist Martin Bodian. Initially the syndrome's clinical presentation included exocrine pancreatic insufficiency (lipomatous replacement of the pancreas) and neutropenia. In 1967 skeletal changes of metaphyseal chondrodysplasia were also described, completing the triad of findings; these abnormalities are present in all affected children and should be viewed as an integral feature of the syndrome, also called Shwachman-Diamond syndrome.

Clinical excellence in academia: perspectives from masterful academic clinicians.

PubMed

Christmas, Colleen; Kravet, Steven J; Durso, Samuel C; Wright, Scott M

2008-09-01

To better understand and characterize clinical excellence in academia by exploring the perspectives of clinically excellent faculty in the top American departments of medicine. Between March 1 and May 31, 2007, 2 investigators conducted in-depth semistructured interviews with 24 clinically excellent Department of Medicine physicians at 8 academic institutions. Interview transcripts were independently analyzed by 2 investigators and compared for agreement. Content analysis identified several major themes that relate to clinical excellence in academia. Physicians hailed from a range of internal medicine specialties; 20 (83%) were associate professors or professors and 8 (33%) were women. The mean percentage of time physicians spent in clinical care was 48%. Eight domains emerged as the major features of clinical excellence in academia: reputation, communication and interpersonal skills, professionalism and humanism, diagnostic acumen, skillful negotiation of the health care system, knowledge, scholarly approach to clinical care, and passion for clinical medicine. Understanding the core elements that contribute to clinical excellence in academia represents a pivotal step to defining clinical excellence in this setting. It is hoped that such work will lead to initiatives aimed at measuring and rewarding clinical excellence in our academic medical centers such that the most outstanding clinicians feel valued and decide to stay in academia to serve as role models for medical trainees.

Clinical Features of Ocular Toxocariasis in Adult Korean Patients.

PubMed

Jee, Donghyun; Kim, Kyu Seop; Lee, Won Ki; Kim, Wungjae; Jeon, Sohee

2016-01-01

To investigate the clinical characteristics and treatment results of adult patients with ocular toxocariasis. A total of 54 consecutive patients who were clinically and serologically diagnosed with ocular toxocariasis were retrospectively reviewed. Among patients, 66.7 and 77.3% showed increases in eosinophil cationic protein (ECP) and total Ig E in serum, respectively. Four eyes (7.2%) initially presented as neuroretinitis with subsequent motile retinal lesion. The recurrence rates in the combination treatment group with albendazole and corticosteroids were significantly lower than those in the steroid-alone group during the mean follow-up of 27.6 months (p = 0.001). The adjunctive test of serum total IgE level may be helpful for the diagnosis of ocular toxocariasis. Ocular toxocariasis should be considered in the differential diagnosis of unilateral neuroretinitis with subsequent motile retinal lesion. Combined treatment with albendazole and corticosteroids appeared to be effective for reducing the recurrence of intraocular inflammation.

Systemic rhabdomyosarcoma presenting as leukemia: case report with ultrastructural study and reviews.

PubMed

Huntrakoon, M; Callaway, L A; Vergara, G G

1987-08-01

A 20-year-old white male was initially suspected clinically and pathologically of having an acute lymphoblastic leukemic process because of fatigue, severe anemia, thrombocytopenia, a leuko-erythroblastic peripheral blood picture, and a diffusely infiltrated bone marrow. Subsequent review of the bone marrow material indicated cytologic features consistent with either an embryonal, undifferentiated small cell mesenchymal malignancy or reticulo-endothelial malignancy. Ultimately, the electron microscopic (EM) study of the tumor proved to be diagnostic of rhabdomyosarcoma. An extensive search for a primary site of rhabdomyosarcoma did not show any lesion, although the genitourinary region was clinically suspected. The clinical course was a rapidly downhill one with extensive bone and CNS involvement. The patient died 5 months later. An autopsy permit was not obtained. This case emphasizes the occasional tendency of rhabdomyosarcoma to masquerade as a hematopoietic malignancy at the time of presentation and the usefulness of EM study in confirming a diagnosis.

Performance, emotion work, and transition: challenging experiences of complementary therapy student practitioners commencing clinical practice.

PubMed

Fixsen, Alison; Ridge, Damien

2012-09-01

Few researchers have explored the clinical experiences of complementary and alternative medical practitioners and students, including the emotion work they perform. In this article, using a constant comparison approach and a heuristic framework (a dramaturgical perspective), we analyze semistructured interviews with 9 undergraduate practitioners in training to examine challenges experienced when students first attend to patients. A feature of students' learning about clinical work concerned performance in a public arena and associated demands placed on the inchoate practitioner. Preliminary patient consultations represented a dramatic rite of passage and initiation into a transitional phase in professional identity. Juggling the roles of student and practitioner within an observed consultation led to anticipatory anxiety, impression management strategies, and conflict with other individuals. Of the coping strategies, participants regarded sharing and feedback from peer groups as most effective in examining and resolving the challenges of becoming a practitioner.

[Basic symptoms in schizophrenia, their clinical study and relevance in research].

PubMed

Miret, Salvador; Fatjó-Vilas, Mar; Peralta, Víctor; Fañanás, Lourdes

2016-01-01

Basic symptoms consist of subtle sub-clinical disturbances subjectively experienced by schizophrenia patients. These are mainly related to drive, affect, thinking and language, perception, memory, motor action, central vegetative functions, control of cognitive processes, and stress tolerance. Initially described by Huber, from a phenomenological approach, basic symptoms are part of the earliest features of schizophrenia, and they can evolve along the course of the disorder. Their assessment during the prodromal phase of the disease (together with ultra-high risk criteria) is one of the 2 main approaches that allow the definition of states of clinical risk for the development of psychosis. The present review provides an updated view of the concept of basic symptoms, highlighting its potential value in establishing neurobiological correlates of interest in aetiopathogenic research. Copyright © 2015 SEP y SEPB. Published by Elsevier España. All rights reserved.

Case report of Graves’ disease manifesting with odynophagia and heartburn

PubMed Central

Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

2015-01-01

Graves’ disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves’ disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment. PMID:26730171

A Case of Delayed Flare-up Allergic Dermatitis Caused by Jellyfish Sting.

PubMed

Manabe, Yasuaki; Mabuchi, Tomotaka; Kawai, Mayu; Ota, Tami; Ikoma, Norihiro; Ozawa, Akira; Horita, Takushi

2014-09-20

A 7-year-old boy, taking lessons at a yacht school at Enoshima in Kanagawa prefecture in Japan, recognized a linear eruption on his left lower leg during practice in August 2012. As it gradually enlarged, he visited a local medical clinic. The eruption initially improved with topical treatment but exacerbated in October of the same year. Although topical treatment was started again, there was minimal improvement, so the patient visited our hospital in December. At his first visit, he had a hard linear nodule on his left lower leg, and papules with excoriation were scattered over the lower limbs. Considering eczema, topical steroid treatment and occlusive dressing technique were started but the nodule remained. Based on the clinical course, clinical features, and laboratory findings, the lesion was considered to be delayed flare-up allergic dermatitis caused by a jellyfish sting [1].

It's a trap! Clinical similarities and subtle ECG differences between takotsubo cardiomyopathy and myocardial infarction.

PubMed

Vivo, Rey P; Krim, Selim R; Hodgson, John

2008-11-01

We describe a 65-year-old woman with a history of hypertension and smoking who presented with an acute episode of chest pain precipitated by severe emotional stress. Her initial electrocardiogram done in the emergency room showed non-specific T wave changes in the lateral leads and her cardiac troponin levels were mildly elevated. Because of her clinical presentation, she was admitted with a presumptive diagnosis of acute myocardial infarction and managed with antiplatelet and anticoagulant therapy. Coronary angiogram did not reveal coronary artery disease and left ventriculography showed findings consistent with apical ballooning syndrome or takotsubo cardiomyopathy. Subsequent electrocardiograms displayed dramatic changes including T wave inversions, QT interval prolongation and U waves. The patient remained asymptomatic and recovered uneventfully. Three weeks post-discharge, an echocardiogram documented resolved left ventricular dysfunction. We describe the clinical features and highlight the electrocardiographic findings that may help differentiate takotsubo cardiomyopathy from myocardial infarction.

Case report of Graves' disease manifesting with odynophagia and heartburn.

PubMed

Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

2015-12-28

Graves' disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves' disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment.

Academic investigator-initiated trials and the challenge of sponsor responsibility: the Cologne Sponsor Model.

PubMed

Georgias, Christine; Grunow, Andrea; Olderog, Miriam; May, Alexander; Paulus, Ursula

2012-12-01

With the amendment to the German Drug Law in 2004, the conduct of clinical trials changed by at least two main aspects: (1) The principles of Good Clinical Practice (GCP) were implemented in the national legislation, and (2) for the first time, the function of the sponsor of a clinical trial and the clinical trial itself have become legally binding definitions. By that, legal differences between industrial and academic clinical trials no longer exist. Clinical trials initiated by investigators have to fulfil the same requirements while the entire sponsor responsibility has to be carried out by the Coordinating Investigator or his institution including implementation of a quality management system according to the GCP. The Cologne Sponsor Model is an effective approach with settings, structures, basic features, action, and reporting lines, as well as funding for clinical trials initiated in an academic environment. The University of Cologne assumes the sponsor responsibility for clinical trials organised by the university researchers according to law. Sponsor's duties are delegated to a central operational unit of the sponsor - the Clinical Trials Center Cologne - which further delegates duties to the Coordinating Investigator. Clinical Trials Center Cologne was established in 2002 to support the performance of clinical trials at the university by offering comprehensive advisory and practical services covering all aspects of study planning and conduct. Furthermore, a specialised division of its quality management department acts as an independent sponsor's Quality Assurance Unit. The Clinical Trials Center Cologne has established a quality management system consisting of different components (1) to enable a reasoned decision to subsequent delegation, (2) for risk-based surveillance of trial conduct (audits, monitoring-checks, and reports), and (3) support and training of the Coordinating Investigator. Double functions of persons and departments in the university environment sometimes make it difficult to define roles in such a model. Therefore, it is necessary to establish clear reporting lines and moreover to monitor regularly and carefully the roles and responsibilities. With the combination of central management and support, control and independence of the researchers, our model represents a 'risk-based' system that offers a sensible option that fulfils the requirements of legal regulations and GCP for trials organised within the university environment.

Asthma-COPD overlap syndrome-Coexistence of chronic obstructive pulmonary disease and asthma in elderly patients and parameters for their differentiation.

PubMed

Tochino, Yoshihiro; Asai, Kazuhisa; Shuto, Taichi; Hirata, Kazuto

2017-03-01

Japan is an aging society, and the number of elderly patients with asthma and chronic obstructive pulmonary disease (COPD) is consequently increasing, with an estimated incidence of approximately 5 million. In 2014, asthma-COPD overlap syndrome (ACOS) was defined by a joint project of Global Initiative for Asthma (GINA) committee and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee. The main aims of this consensus-based document are to assist clinicians, especially those in primary care or nonpulmonary specialties. In this article, we discussed parameters to differentiate asthma and COPD in elderly patients and showed prevalence, clinical features and treatment of ACOS on the basis of the guidelines of GINA and GOLD. Furthermore, we showed also referral for specialized investigations.

U-BIOPRED: evaluation of the value of a public-private partnership to industry.

PubMed

Riley, John H; Erpenbeck, Veit J; Matthews, J G; Holweg, C T J; Compton, C; Seibold, W; Higenbottam, T; Wagers, S S; Rowe, A; Myles, D

2018-06-21

Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) was initiated in the first year of the Innovative Medicines Initiative (IMI). It was an ambitious plan to tackle the understanding of asthma through an integration of clinical and multi-'omics approaches that necessitated the bringing together of industry, academic, and patient representatives because it was too large to be managed by any one of the partners in isolation. It was a novel experience for all concerned. In this review, we describe the main features of the U-BIOPRED experience from the industry perspective. We list some of the key advantages and learnings from the perspective of the authors, and also improvements that we feel could be made in future projects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of symptom and functional domains that fibromyalgia patients would like to see improved: a cluster analysis.

PubMed

Bennett, Robert M; Russell, Jon; Cappelleri, Joseph C; Bushmakin, Andrew G; Zlateva, Gergana; Sadosky, Alesia

2010-06-28

The purpose of this study was to determine whether some of the clinical features of fibromyalgia (FM) that patients would like to see improved aggregate into definable clusters. Seven hundred and eighty-eight patients with clinically confirmed FM and baseline pain > or =40 mm on a 100 mm visual analogue scale ranked 5 FM clinical features that the subjects would most like to see improved after treatment (one for each priority quintile) from a list of 20 developed during focus groups. For each subject, clinical features were transformed into vectors with rankings assigned values 1-5 (lowest to highest ranking). Logistic analysis was used to create a distance matrix and hierarchical cluster analysis was applied to identify cluster structure. The frequency of cluster selection was determined, and cluster importance was ranked using cluster scores derived from rankings of the clinical features. Multidimensional scaling was used to visualize and conceptualize cluster relationships. Six clinical features clusters were identified and named based on their key characteristics. In order of selection frequency, the clusters were Pain (90%; 4 clinical features), Fatigue (89%; 4 clinical features), Domestic (42%; 4 clinical features), Impairment (29%; 3 functions), Affective (21%; 3 clinical features), and Social (9%; 2 functional). The "Pain Cluster" was ranked of greatest importance by 54% of subjects, followed by Fatigue, which was given the highest ranking by 28% of subjects. Multidimensional scaling mapped these clusters to two dimensions: Status (bounded by Physical and Emotional domains), and Setting (bounded by Individual and Group interactions). Common clinical features of FM could be grouped into 6 clusters (Pain, Fatigue, Domestic, Impairment, Affective, and Social) based on patient perception of relevance to treatment. Furthermore, these 6 clusters could be charted in the 2 dimensions of Status and Setting, thus providing a unique perspective for interpretation of FM symptomatology.

Formula Milk Supplementation on the Postnatal Ward: A Cross-Sectional Analytical Study

PubMed Central

Biggs, Kirsty V.; Hurrell, Katherine; Matthews, Eleanor

2018-01-01

Breastfeeding rates are low in the UK, where approximately one quarter of infants receive a breastmilk substitute (BMS) in the first week of life. We investigated the reasons for early BMS use in two large maternity units in the UK, in order to understand the reasons for the high rate of early BMS use in this setting. Data were collected through infant feeding records, as well as maternal and midwife surveys in 2016. During 2016, 28% of infants received a BMS supplement prior to discharge from the hospital maternity units with only 10% supplementation being clinically indicated. There was wide variation in BMS initiation rates between different midwives, which was associated with ward environment and midwife educational level. Specific management factors associated with non-clinically indicated initiation of BMS were the absence of skin-to-skin contact within an hour of delivery (p = 0.01), and no attendance at an antenatal breastfeeding discussion (p = 0.01). These findings suggest that risk of initiating a BMS during postnatal hospital stay is largely modifiable. Concordance with UNICEF Baby Friendly 10 steps, attention to specific features of the postnatal ward working environment, and the targeting of midwives and mothers with poor educational status may all lead to improved exclusive breastfeeding rates at hospital discharge. PMID:29757936

Formula Milk Supplementation on the Postnatal Ward: A Cross-Sectional Analytical Study.

PubMed

Biggs, Kirsty V; Hurrell, Katherine; Matthews, Eleanor; Khaleva, Ekaterina; Munblit, Daniel; Boyle, Robert J

2018-05-14

Breastfeeding rates are low in the UK, where approximately one quarter of infants receive a breastmilk substitute (BMS) in the first week of life. We investigated the reasons for early BMS use in two large maternity units in the UK, in order to understand the reasons for the high rate of early BMS use in this setting. Data were collected through infant feeding records, as well as maternal and midwife surveys in 2016. During 2016, 28% of infants received a BMS supplement prior to discharge from the hospital maternity units with only 10% supplementation being clinically indicated. There was wide variation in BMS initiation rates between different midwives, which was associated with ward environment and midwife educational level. Specific management factors associated with non-clinically indicated initiation of BMS were the absence of skin-to-skin contact within an hour of delivery ( p = 0.01), and no attendance at an antenatal breastfeeding discussion ( p = 0.01). These findings suggest that risk of initiating a BMS during postnatal hospital stay is largely modifiable. Concordance with UNICEF Baby Friendly 10 steps, attention to specific features of the postnatal ward working environment, and the targeting of midwives and mothers with poor educational status may all lead to improved exclusive breastfeeding rates at hospital discharge.

Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer

PubMed Central

Chavez-Gonzalez, Antonieta; Bakhshinejad, Babak; Pakravan, Katayoon

2018-01-01

Background Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are characterized by high self-renewal and multi-lineage differentiation capacities. CSCs are thought to play indispensable roles in the initiation, progression and metastasis of many types of cancer. Leukemias are thought to be initiated and maintained by a specific sub-type of CSC, the leukemia stem cell (LSC). An important feature of LSCs is their resistance to standard therapy, which may lead to relapse. Increasing efforts are aimed at developing novel therapeutic strategies that selectively target LSCs, while sparing their normal counterparts and, thus, minimizing adverse treatment-associated side-effects. These LSC targeting therapies aim to eradicate LSCs through affecting mechanisms that control their survival, self-renewal, differentiation, proliferation and cell cycle progression. Some LSC targeting therapies have already been proven successful in pre-clinical studies and they are now being tested in clinical studies, mainly in combination with conventional treatment regimens. Conclusions A growing body of evidence indicates that the selective targeting of LSCs represents a promising approach to improve disease outcome. Beyond doubt, the CSC hypothesis has added a new dimension to the area of anticancer research, thereby paving the way for shaping a new trend in cancer therapy. PMID:27678246

Spontaneous rectus sheath hematoma in pregnancy and a systematic anatomical workup of rectus sheath hematoma: a case report.

PubMed

Eckhoff, Kerstin; Wedel, Thilo; Both, Marcus; Bas, Kayhan; Maass, Nicolai; Alkatout, Ibrahim

2016-10-19

Rectus sheath hematoma is a rare clinical diagnosis, particularly in pregnancy. Due to unspecific symptoms, misdiagnosis is likely and could potentially endanger a patient as well as her fetus. A 26-year-old white woman presented with mild right-sided abdominal pain, which increased during palpation and movement, at 26 + 3 weeks' gestational age. Ultrasound imaging initially showed a round and well-demarcated structure, which appeared to be in contact with her uterine wall, leading to a suspected diagnosis of an infarcted leiomyoma. However, she reported increasing levels of pain and laboratory tests showed a significant drop in her initially normal hemoglobin level. A magnetic resonance imaging scan finally revealed a large type III rectus sheath hematoma on the right side. Because of progressive blood loss into her rectus sheath under conservative therapy, with a significant further decrease in her hemoglobin levels, surgical treatment via right-sided paramedian laparotomy was initiated. During the operation the arterial bleed could be ligated. She eventually achieved complete convalescence and delivered a healthy newborn spontaneously after 40 weeks of gestation. This case report highlights the clinical and diagnostic features of rectus sheath hematoma and shows the anatomical aspects of the rectus sheath, simplifying early and correct diagnosis.

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents

PubMed Central

Ferkol, Thomas W.; Davis, Stephanie D.; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D.; Sagel, Scott D.; Milla, Carlos; Olivier, Kenneth N.; Sullivan, Kelli M.; Zariwala, Maimoona A.; Pittman, Jessica E.; Shapiro, Adam J.; Carson, Johnny L.; Krischer, Jeffrey; Hazucha, Milan J.

2016-01-01

Rationale: Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. Objectives: To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Methods: Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0–18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as “definite PCD” (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), “probable/possible PCD” (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and “other diagnosis or undefined.” Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. Measurements and Main Results: From 534 participants 18 years of age and younger, 205 were identified as having “definite PCD” (including 164 with two mutations in a PCD-associated gene), 187 were categorized as “other diagnosis or undefined,” and 142 were defined as having “probable/possible PCD.” Participants with “definite PCD” were compared with the “other diagnosis or undefined” group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Conclusions: Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167). PMID:27070726

The influence of gender on respiratory outcomes in children with bronchopulmonary dysplasia during the first 3 years of life.

PubMed

Collaco, Joseph M; Aherrera, Angela D; McGrath-Morrow, Sharon A

2017-02-01

Since premature males are more likely to be diagnosed with bronchopulmonary dysplasia we hypothesized that differences in respiratory outcomes after initial hospital discharge and during the first 3 years of life would exist between females and males diagnosed with BPD. Subjects with the diagnosis of BPD were recruited from the Johns Hopkins Bronchopulmonary Dysplasia Clinic between 2008 and 2014. Clinical features were assessed through chart review (n = 482). Respiratory morbidities were assessed by caregiver questionnaires at clinic visits (n = 429), including emergency department visits, hospital admissions, systemic steroid use, and antibiotic use for respiratory reasons since the last BPD clinic visit or after initial hospital discharge if assessed at the first visit. Male infants weighed significantly more at birth, had higher birth weight percentiles and were more likely to be non-white compared to female infants. The frequency of ever acute care use was 36.9% for emergency department visits, 27.4% for hospital admissions, 36.9% for systemic steroid use, and 40.5% for antibiotic use for a respiratory illness. No differences in respiratory morbidities were found between males and females. Females however, tended to be weaned from supplemental oxygen over 3 months later than males. Compared to females with BPD, males were more likely to weigh more, have higher birth weight percentiles and be non-white. After initial hospital discharge, there were no difference in respiratory morbidities between males and females with BPD. Female infants however were more likely to be weaned from supplemental oxygen at a later age than male infants. Pediatr Pulmonol. 2017;52:217-224. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

INITIATE: An Intelligent Adaptive Alert Environment.

PubMed

Jafarpour, Borna; Abidi, Samina Raza; Ahmad, Ahmad Marwan; Abidi, Syed Sibte Raza

2015-01-01

Exposure to a large volume of alerts generated by medical Alert Generating Systems (AGS) such as drug-drug interaction softwares or clinical decision support systems over-whelms users and causes alert fatigue in them. Some of alert fatigue effects are ignoring crucial alerts and longer response times. A common approach to avoid alert fatigue is to devise mechanisms in AGS to stop them from generating alerts that are deemed irrelevant. In this paper, we present a novel framework called INITIATE: an INtellIgent adapTIve AlerT Environment to avoid alert fatigue by managing alerts generated by one or more AGS. We have identified and categories the lifecycle of different alerts and have developed alert management logic as per the alerts' lifecycle. Our framework incorporates an ontology that represents the alert management strategy and an alert management engine that executes this strategy. Our alert management framework offers the following features: (1) Adaptability based on users' feedback; (2) Personalization and aggregation of messages; and (3) Connection to Electronic Medical Records by implementing a HL7 Clinical Document Architecture parser.

The first Korean patient with Potocki-Shaffer syndrome: a rare cause of multiple exostoses.

PubMed

Sohn, Young Bae; Yim, Shin-Young; Cho, Eun-Hae; Kim, Ok-Hwa

2015-02-01

Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)×1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered.

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome.

PubMed

Boyden, Lynn M; Kam, Chen Y; Hernández-Martín, Angela; Zhou, Jing; Craiglow, Brittany G; Sidbury, Robert; Mathes, Erin F; Maguiness, Sheilagh M; Crumrine, Debra A; Williams, Mary L; Hu, Ronghua; Lifton, Richard P; Elias, Peter M; Green, Kathleen J; Choate, Keith A

2016-01-15

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Insulin initiation status of primary care physicians in Turkey, barriers to insulin initiation and knowledge levels about insulin therapy: A multicenter cross-sectional study.

PubMed

Ates, Elif; Set, Turan; Saglam, Zuhal; Tekin, Nil; Karatas Eray, Irep; Yavuz, Erdinc; Sahin, Mustafa Kursat; Selcuk, Engin Burak; Cadirci, Dursun; Cubukcu, Mahcube

2017-10-01

Our aim was to evaluate the insulin initiation status, barriers to insulin initiation and knowledge levels about treatment administered by primary care physicians (PCP). We conducted our study in accordance with a multicenter, cross-sectional design in Turkey, between July 2015 and July 2016. A questionnaire inquiring demographic features, status of insulin initiation, obstacles to insulin initiation and knowledge about therapy of the PCPs was administered during face-to-face interviews. 84 PCPs (19%) (n=446, mean age=41.5±8.4years, 62.9% male and 90.0% ministry certified family physicians) initiated insulin therapy in the past. Most of the stated primary barriers (51.9%, n=230) were due to the physicians. The most relevant barrier was "lack of clinical experience" with a rate of 19% (n=84 of the total). The average total knowledge score was 5.7±2.0 for the family medicine specialist, and 3.8±2.1 for the ministry certified family physicians (p=0.000, maximum knowledge score could be 10). The status of insulin initiation in Turkey by the primary care physicians is inadequate. Medical education programs and health care systems may require restructuring to facilitate insulin initiation in primary care. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Intraoperative imaging during Mohs surgery with reflectance confocal microscopy: initial clinical experience

NASA Astrophysics Data System (ADS)

Flores, Eileen S.; Cordova, Miguel; Kose, Kivanc; Phillips, William; Rossi, Anthony; Nehal, Kishwer; Rajadhyaksha, Milind

2015-06-01

Mohs surgery for the removal of nonmelanoma skin cancers (NMSCs) is performed in stages, while being guided by the examination for residual tumor with frozen pathology. However, preparation of frozen pathology at each stage is time consuming and labor intensive. Real-time intraoperative reflectance confocal microscopy (RCM), combined with video mosaicking, may enable rapid detection of residual tumor directly in the surgical wounds on patients. We report our initial experience on 25 patients, using aluminum chloride for nuclear contrast. Imaging was performed in quadrants in the wound to simulate the Mohs surgeon's examination of pathology. Images and videos of the epidermal and dermal margins were found to be of clinically acceptable quality. Bright nuclear morphology was identified at the epidermal margin and detectable in residual NMSC tumors. The presence of residual tumor and normal skin features could be detected in the peripheral and deep dermal margins. Intraoperative RCM imaging may enable detection of residual tumor directly on patients during Mohs surgery, and may serve as an adjunct for frozen pathology. Ultimately, for routine clinical utility, a stronger tumor-to-dermis contrast may be necessary, and also a smaller microscope with an automated approach for imaging in the entire wound in a rapid and controlled manner.

Duration and structure of unaccompanied (dyadic) and accompanied (triadic) initial outpatient consultations in a specialist seizure clinic.

PubMed

Robson, Catherine; Drew, Paul; Reuber, Markus

2013-06-01

This study explores differences in the duration and structure of unaccompanied (dyadic) and accompanied (triadic) initial (diagnostic) outpatient consultations in a specialist seizure clinic. This is the first known study to explore this topic quantitatively by analyzing the discourse space taken up by the different participants in real clinical encounters. We did not observe significant differences between the duration of accompanied and unaccompanied interactions (p=0.589). Results suggest that patients occupy proportionally less discourse space (measured by the number of words produced) in accompanied interactions than in unaccompanied interactions (56.9% versus 28.3%, p ≤ 0.0001). In accompanied interactions, there is a weak negative correlation between the discourse space of patients and that of doctors (rs=-0.43, p=0.017) and a moderate to strong negative correlation with the discourse spaces of companions (rs=-0.64, p=0.001). These findings indicate that the presence of a companion may reduce opportunities for doctors to observe the interactional, linguistic, and topical features of seizure patient talk, whose differential diagnostic value has been described in a number of previous publications, or for patients to raise issues they want to talk about. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children.

PubMed

Buckingham, Steven C; Marshall, Gary S; Schutze, Gordon E; Woods, Charles R; Jackson, Mary Anne; Patterson, Lori E R; Jacobs, Richard F

2007-02-01

To describe the clinical characteristics and course of children with laboratory-diagnosed Rocky Mountain spotted fever (RMSF) and to identify clinical findings independently associated with adverse outcomes of death or discharge with neurologic deficits. Retrospective chart review of 92 patients at six institutions in the southeastern and southcentral United States from 1990 to 2002. Statistical analyses used descriptive statistics and multiple logistic regression. Children with RMSF presented to study institutions after a median of 6 days of symptoms, which most commonly included fever (98%), rash (97%), nausea and/or vomiting (73%), and headache (61%); no other symptom or sign was present in >50% of children. Only 49% reported antecedent tick bites. Platelet counts were <150,000/mm3 in 59% of children, and serum sodium concentrations were <135 mEq/dL in 52%. Although 86% sought medical care before admission, only 4 patients received anti-rickettsial therapy during this time. Three patients died, and 13 survivors had neurologic deficits at discharge. Coma and need for inotropic support and intravenous fluid boluses were independently associated with adverse outcomes. Children with RMSF generally present with fever and rash. Delays in diagnosis and initiation of appropriate therapy are unacceptably common. Prognosis is guarded in those with hemodynamic instability or neurologic compromise at initiation of therapy.

Tuberculous Meningitis in Children and Adults: New Insights for an Ancient Foe.

PubMed

Mezochow, Alyssa; Thakur, Kiran; Vinnard, Christopher

2017-09-20

Tuberculous meningitis is the most devastating manifestation of infection with Mycobacterium tuberculosis and represents a medical emergency. Approximately one half of tuberculous meningitis patients die or suffer severe neurologic disability. The goal of this review will be to review the pathogenic, clinical, and radiologic features of tuberculous meningitis and to highlight recent advancements in translational and clinical science. Pharmacologic therapy includes combination anti-tuberculosis drug regimens and adjunctive corticosteroids. It is becoming clear that a successful treatment outcome depends on an immune response that is neither too weak nor overly robust, and genetic determinants of this immune response may identify which patients will benefit from adjunctive corticosteroids. Recent clinical trials of intensified anti-tuberculosis treatment regimens conducted in Indonesia and Vietnam, motivated by the pharmacologic challenges of treating M. tuberculosis infections of the central nervous system, have yielded conflicting results regarding the survival benefit of intensified treatment regimens. More consistent findings have been observed regarding the relationship between initial anti-tuberculosis drug resistance and mortality among tuberculous meningitis patients. Prompt initiation of anti-tuberculosis treatment for all suspected cases remains a key aspect of management. Priorities for research include the improvement of diagnostic testing strategies and the optimization of host-directed and anti-tuberculosis therapies.

Basal cell carcinoma of the vulva: a case series.

PubMed

Mulvany, Nicholas J; Rayoo, Mukta; Allen, David G

2012-10-01

To review the diagnostic features and characteristics of an uncommon tumour, basal cell carcinoma (BCC) of the vulva. The clinical and pathological details of six vulvar BCCs were reviewed. Four of the BCCs arose in isolation, one was combined with vulvar Paget's disease and another was intimately associated with a poorly differentiated squamous cell carcinoma. The average age of the six patients was 76 years (75 years for 'isolated' BCC; 78 years for BCC 'mixed' with other lesions). The duration of symptoms averaged 13 months in 'isolated' BCC but 24 months in 'mixed' BCC. Vulvar pruritus was the most common presenting complaint in the four cases of 'isolated' BCC. The initial biopsies included shave (× 2) or punch biopsies (× 4). Definitive surgery included excisional biopsy (× 2) or a wide local excision (× 3). In the five assessable tumours, the maximum tumour diameter averaged 19.8 mm (range 11-36 mm). In the sixth patient the BCC was contiguous with a 70 mm, unresectable, poorly differentiated squamous cell carcinoma which was treated by radiotherapy alone. : Although the histological diagnosis of vulvar BCC was straightforward in some of our cases, others presented difficulties due to non-representative initial biopsies, insufficient clinical information or contiguity with lesions of greater clinical significance such as Paget's disease or squamous cell carcinoma.

Non-specific gastrointestinal features: Could it be Fabry disease?

PubMed

Hilz, Max J; Arbustini, Eloisa; Dagna, Lorenzo; Gasbarrini, Antonio; Goizet, Cyril; Lacombe, Didier; Liguori, Rocco; Manna, Raffaele; Politei, Juan; Spada, Marco; Burlina, Alessandro

2018-05-01

Non-specific gastrointestinal symptoms, including pain, diarrhoea, nausea, and vomiting, can be the first symptoms of Fabry disease. They may suggest more common disorders, e.g. irritable bowel syndrome or inflammatory bowel disease. The confounding clinical presentation and rarity of Fabry disease often cause long diagnostic delays and multiple misdiagnoses. Therefore, specialists involved in the clinical evaluation of non-specific upper and lower gastrointestinal symptoms should recognize Fabry disease as a possible cause of the symptoms, and should consider Fabry disease as a possible differential diagnosis. When symptoms or family history suggest Fabry disease, in men, low alpha-galactosidase A enzyme levels, and in women, specific Fabry mutations confirm the diagnosis. In addition to symptomatic treatments, disease-specific enzyme replacement therapy with recombinant human alpha-galactosidase A enzyme or chaperone therapy (migalastat) in patients with amenable mutations can improve the disease, including gastrointestinal symptoms, and should be initiated as early as possible after Fabry disease has been confirmed; starting enzyme replacement therapy at as young an age as possible after diagnosis improves long-term clinical outcomes. Improved diagnostic tools, such as a modified gastrointestinal symptom rating scale, may facilitate diagnosing Fabry disease in patients with gastrointestinal symptoms of unknown cause and thus assure timely initiation of disease-specific treatment. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Application of Smart Infrastructure Systems approach to precision medicine.

PubMed

Govindaraju, Diddahally R; Annaswamy, Anuradha M

2015-12-01

All biological variation is hierarchically organized dynamic network system of genomic components, organelles, cells, tissues, organs, individuals, families, populations and metapopulations. Individuals are axial in this hierarchy, as they represent antecedent, attendant and anticipated aspects of health, disease, evolution and medical care. Humans show individual specific genetic and clinical features such as complexity, cooperation, resilience, robustness, vulnerability, self-organization, latent and emergent behavior during their development, growth and senescence. Accurate collection, measurement, organization and analyses of individual specific data, embedded at all stratified levels of biological, demographic and cultural diversity - the big data - is necessary to make informed decisions on health, disease and longevity; which is a central theme of precision medicine initiative (PMI). This initiative also calls for the development of novel analytical approaches to handle complex multidimensional data. Here we suggest the application of Smart Infrastructure Systems (SIS) approach to accomplish some of the goals set forth by the PMI on the premise that biological systems and the SIS share many common features. The latter has been successfully employed in managing complex networks of non-linear adaptive controls, commonly encountered in smart engineering systems. We highlight their concordance and discuss the utility of the SIS approach in precision medicine programs.

Epilepsy Characteristics and Clinical Outcome in Patients With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS).

PubMed

Lee, Ha Neul; Eom, Soyong; Kim, Se Hoon; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Heung Dong; Lee, Young-Mock

2016-11-01

Epileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) are heterogeneous with no pathognomonic features. We reviewed epilepsy characteristics and clinical outcome exclusively in a pediatric population. Twenty-two children and adolescents (13 males) with confirmed mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes due to mitochondrial DNA A3243G mutation and epilepsy were recruited. Clinical data including seizure semiology, treatment response, neuroimaging findings, and electroencephalography were analyzed. We also examined the effect of the age at seizure onset and initial symptoms on the clinical variables. Seizure semiology and electroencephalography abnormalities showed no syndrome-specific findings. Focal seizures occurred in 21 of 22 subjects (95.5%), whereas generalized seizures developed in seven of 22 subjects (31.8%). Twenty of 22 subjects (90.9%) achieved partial to complete reduction of clinical seizures for more than one year with a combination of more than two antiepileptic drugs. The subgroup with earlier seizure onset presented significantly earlier and showed significantly higher rates of drug-resistant epilepsy compared with the late onset group, although there were no significant differences in the initial symptoms. The subjects with severe epileptic conditions tended to have more severe clinical dysfunction and more severe organ involvement. Both focal and generalized seizures occurred in patients with MELAS. Epilepsy in this population is drug resistant, but a certain degree of clinical seizure reduction was achievable with antiepileptic drugs, with more favorable outcomes than historically expected. Close observation and active epilepsy treatment of individuals with MELAS episodes and earlier seizure onset might improve the prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry

PubMed Central

Mayosi, Bongani M; Wiysonge, Charles Shey; Ntsekhe, Mpiko; Volmink, Jimmy A; Gumedze, Freedom; Maartens, Gary; Aje, Akinyemi; Thomas, Baby M; Thomas, Kandathil M; Awotedu, Abolade A; Thembela, Bongani; Mntla, Phindile; Maritz, Frans; Blackett, Kathleen Ngu; Nkouonlack, Duquesne C; Burch, Vanessa C; Rebe, Kevin; Parish, Andy; Sliwa, Karen; Vezi, Brian Z; Alam, Nowshad; Brown, Basil G; Gould, Trevor; Visser, Tim; Shey, Muki S; Magula, Nombulelo P; Commerford, Patrick J

2006-01-01

Background The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. Methods Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. Results A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. Conclusion Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease. PMID:16396690

ED presentations of acute renal infarction.

PubMed

Huang, Chien-Cheng; Lo, Hong-Chang; Huang, Hsien-Hao; Kao, Wei-Fong; Yen, David Hung-Tsang; Wang, Lee-Min; Huang, Chun-I; Lee, Chen-Hsen

2007-02-01

The objective of the study was to investigate initial clinical characteristics that can suggest an early diagnosis of patients with acute renal infarction presenting with flank and/or abdominal pain in the emergency department (ED). From January 1, 1996, through December 31, 2005, 20 adult patients with renal infarction diagnosed by contrast-enhanced computed tomography in the ED were enrolled. Medical records, including demographic data, risk factors for thromboembolism, initial clinical presentations, laboratory data, treatment programs and outcomes, were retrospectively reviewed and analyzed. Mean patient age was 60.3 years (range, 21-80). The estimated incidence of renal infarction was 0.004% (20 of 481,540) among the ED census. The median time of onset of symptoms before the ED visit was 31 hours (range, 1-285). Eighteen patients (90%) had a history of more than 1 risk factor for thromboembolic events. In clinical presentations, all the patients had either abdominal or flank pain and tenderness. Nineteen patients (95%) had an elevated serum lactate dehydrogenase level with a mean +/- SD of 812.1 +/- 569.4 U/L. Sixteen patients (80%) presented with the triad--persisting flank or abdominal pain/tenderness, elevated serum lactate dehydrogenase level, and proteinuria. Among all 20 patients, 10 patients (50%) were diagnosed as having renal infarction at the initial ED visit. No specific clinical characteristics could be identified to distinguish those patients diagnosed early and those with delayed diagnosis. All 20 patients received medical treatment with coumadin, which was given in combination with heparin treatment in 11, peripheral intravenous and/or local intra-arterial thrombolytics with urokinase in 5, and mitral valve replacement in 1. No patient died. Although 4 patients had a mildly elevated serum creatinine level (>1.5 mg/dL) during hospitalization, none of them needs dialysis after more than 1 year of follow-up. In this study, we delineated specifically clinical features for emergency physicians to raise their suspicion index for an early diagnosis of patients with renal infarction, a disease which is uncommon and is usually delayed or missed at initial ED presentation.

Dental Implant Macro-Design Features Can Impact the Dynamics of Osseointegration.

PubMed

Vivan Cardoso, Marcio; Vandamme, Katleen; Chaudhari, Amol; De Rycker, Judith; Van Meerbeek, Bart; Naert, Ignace; Duyck, Joke

2015-08-01

The purpose of this study was to compare the clinical performance of two dental implant types possessing a different macro-design in the in vivo pig model. Titanium Aadva(TM) implants (GC, Tokyo, Japan) were compared with OsseoSpeed(TM) implants (Astra, Mölndal, Sweden), with the Aadva implant displaying significant larger inter-thread dimensions than the OsseoSpeed implant. Implants were installed in the parietal bone of 12 domestic pigs and left for healing for either 1 or 3 months. Implant osseointegration was evaluated by quantitative histology (bone volume relative to the tissue volume [BV/TV]; bone-to-implant contact [BIC]) for distinct implant regions (collar, body, total implant length) with specific implant thread features. The Wilcoxon-Mann-Whitney nonparametric test with α = 0.05 was performed. An inferior amount of bone enveloping the Aadva implant compared with the OsseoSpeed implant was observed, in particular at the implant body part with its considerable inter-thread gaps (p < .05). Concomitantly, the Aadva macro-design negatively affected the amount of bone in direct contact with the implant for this specific implant part (p < .05), and resulted in an overall impaired implant osseointegration at the initial healing stage (total implant length; 1-month healing; p < .05). Although the Aadva implant displayed a clinically acceptable level of osseointegration, the findings demonstrate that implant macro-design features can impact the dynamics of implant osseointegration. Consideration of specific implant macro-design features should be made relative to the biological and mechanical microenvironment. © 2013 Wiley Periodicals, Inc.

Increasing Capacity for Innovation in Bureaucratic Primary Care Organizations: A Whole System Participatory Action Research Project

PubMed Central

Thomas, Paul; McDonnell, Juliet; McCulloch, Janette; While, Alison; Bosanquet, Nick; Ferlie, Ewan

2005-01-01

PURPOSE We wanted to identify what organizational features support innovation in Primary Care Groups (PCGs). METHODS Our study used a whole system participatory action research model. Four research teams provided complementary insights. Four case study PCGs were analyzed. Two had an intervention to help local facilitators reflect on their work. Data included 70 key informant interviews, observations of clinical governance interventions and committee meetings, analysis of written materials, surveys and telephone interviews of London Primary Care Organizations, interviews with 20 nurses, and interviews with 6 finance directors. A broad range of stakeholders reviewed data at annual conferences and formed conclusions about trustworthy principles. Sequential research phases were refocused in the light of these conclusions and in response to the changing political context. RESULTS Five features were associated with increased organizational capacity for innovation: (1) clear structures and a vision for corporate and clinical governance; (2) multiple opportunities for people to reflect and learn at all levels of the organization, and connections between these “learning spaces”; (3) both clinicians and managers in leadership roles that encourage participation; (4) the right timing for an initiative and its adaptation to the local context; and (5) external facilitation that provides opportunities for people to make sense of their experiences. Low morale was commonly attributed to 3 features: (1) overwhelming pace of reform, (2) inadequate staff experience and supportive infrastructure, and (3) financial deficits. CONCLUSIONS These features together may support innovation in other primary care bureaucracies. The research methodology enabled people from different backgrounds to make sense of diverse research insights. PMID:16046563

Increasing capacity for innovation in bureaucratic primary care organizations: a whole system participatory action research project.

PubMed

Thomas, Paul; McDonnell, Juliet; McCulloch, Janette; While, Alison; Bosanquet, Nick; Ferlie, Ewan

2005-01-01

We wanted to identify what organizational features support innovation in Primary Care Groups (PCGs). Our study used a whole system participatory action research model. Four research teams provided complementary insights. Four case study PCGs were analyzed. Two had an intervention to help local facilitators reflect on their work. Data included 70 key informant interviews, observations of clinical governance interventions and committee meetings, analysis of written materials, surveys and telephone interviews of London Primary Care Organizations, interviews with 20 nurses, and interviews with 6 finance directors. A broad range of stakeholders reviewed data at annual conferences and formed conclusions about trustworthy principles. Sequential research phases were refocused in the light of these conclusions and in response to the changing political context. Five features were associated with increased organizational capacity for innovation: (1) clear structures and a vision for corporate and clinical governance; (2) multiple opportunities for people to reflect and learn at all levels of the organization, and connections between these "learning spaces"; (3) both clinicians and managers in leadership roles that encourage participation; (4) the right timing for an initiative and its adaptation to the local context; and (5) external facilitation that provides opportunities for people to make sense of their experiences. Low morale was commonly attributed to 3 features: (1) overwhelming pace of reform, (2) inadequate staff experience and supportive infrastructure, and (3) financial deficits. These features together may support innovation in other primary care bureaucracies. The research methodology enabled people from different backgrounds to make sense of diverse research insights.

Catatonia in Psychotic Patients: Clinical Features and Treatment Response

PubMed Central

England, Mary L.; Öngür, Dost; Konopaske, Glenn T.; Karmacharya, Rakesh

2012-01-01

We report clinical features and treatment response in 25 patients with catatonia admitted to an inpatient psychiatric unit specializing in psychotic disorders. ECT, benzodiazepines, and clozapine had beneficial effects on catatonic features, while typical antipsychotics resulted in clinical worsening. PMID:21677256

Fluorescence guided evaluation of photodynamic therapy as acne treatment

NASA Astrophysics Data System (ADS)

Ericson, Marica B.; Horfelt, Camilla; Cheng, Elaine; Larsson, Frida; Larko, Olle; Wennberg, Ann-Marie

2005-08-01

Photodynamic therapy (PDT) is an attractive alternative treatment for patients with acne because of its efficiency and few side effects. Propionibacterium acnes (P.acnes) are bacteria present in the skin, which produce endogenous porphyrins that act as photosensitisers. In addition, application of aminolaevulinic acid or its methyl ester (mALA) results in increased accumulation of porphyrins in the pilosebaceous units. This makes it possible to treat acne with PDT. This initial study investigates the possibility of fluorescence imaging as assessment tool in adjunct to PDT of patients with acne. Twenty-four patients with acne on the cheeks have been treated with PDT with and without mALA. Fluorescence images have been obtained before and after treatment. The clinical acne score was assessed as base line before PDT, and at every follow up visit. Additionally the amount of P.acnes was determined. The clinical evaluation showed a general improvement of acne, even though no difference between treatment with and without mALA was observed. By performing texture analysis and multivariate data analsysis on the fluorescence images, the extracted texture features were found to correlate with the corresponding clinical assessment (67%) and amount of P.acnes (72%). The analysis showed that features describing the highly fluorescent pores could be related to the clinical assessment. This result suggests that fluorescence imaging can be used as an objective assessment of acne, but further improvement of the technique is possible, for example by including colour images.

Medical home characteristics and the pediatric patient experience.

PubMed

Burnet, Deborah; Gunter, Kathryn E; Nocon, Robert S; Gao, Yue; Jin, Janel; Fairchild, Paige; Chin, Marshall H

2014-11-01

The patient-centered medical home (PCMH) has roots in pediatrics, yet we know little about the experience of pediatric patients in PCMH settings. To examine the association between clinic PCMH characteristics and pediatric patient experience as reported by parents. We assessed the cross-sectional correlation between clinic PCMH characteristics and pediatric patient experience in 24 clinics randomly selected from the Safety Net Medical Home Initiative, a 5-state PCMH demonstration project. PCMH characteristics were measured with surveys of randomly selected providers and staff; surveys generated 0 (worst) to 100 (best) scores for 5 subscales, and a total score. Patient experience was measured through surveying parents of pediatric patients. Questions from the Consumer Assessment of Healthcare Providers and Systems-Clinician and Group instrument produced 4 patient experience measures: timeliness, physician communication, staff helpfulness, and overall rating. To investigate the relationship between PCMH characteristics and patient experience, we used generalized estimating equations with an exchangeable correlation structure. We included 440 parents and 214 providers and staff in the analysis. Total PCMH score was not associated with parents' assessment of patient experience; however, PCMH subscales were associated with patient experience in different directions. In particular, quality improvement activities undertaken by clinics were strongly associated with positive ratings of patient experience, whereas patient care management activities were associated with more negative reports of patient experience. Future work should bolster features of the PCMH that work well for patients while investigating which PCMH features negatively impact patient experience, to yield a better patient experience overall.

Development of a novel imaging informatics-based system with an intelligent workflow engine (IWEIS) to support imaging-based clinical trials

PubMed Central

Wang, Ximing; Liu, Brent J; Martinez, Clarisa; Zhang, Xuejun; Winstein, Carolee J

2015-01-01

Imaging based clinical trials can benefit from a solution to efficiently collect, analyze, and distribute multimedia data at various stages within the workflow. Currently, the data management needs of these trials are typically addressed with custom-built systems. However, software development of the custom- built systems for versatile workflows can be resource-consuming. To address these challenges, we present a system with a workflow engine for imaging based clinical trials. The system enables a project coordinator to build a data collection and management system specifically related to study protocol workflow without programming. Web Access to DICOM Objects (WADO) module with novel features is integrated to further facilitate imaging related study. The system was initially evaluated by an imaging based rehabilitation clinical trial. The evaluation shows that the cost of the development of system can be much reduced compared to the custom-built system. By providing a solution to customize a system and automate the workflow, the system will save on development time and reduce errors especially for imaging clinical trials. PMID:25870169

New drugs and new toxicities: pembrolizumab-induced myocarditis.

PubMed

Inayat, Faisal; Masab, Muhammad; Gupta, Sorab; Ullah, Waqas

2018-01-23

Pembrolizumab is an immune checkpoint inhibitor that significantly improves clinical outcomes in numerous solid organ malignancies. Despite successful therapeutic responses, this new drug comes with a constellation of adverse reactions. Herein, we chronicle the case of a patient with metastatic non-small-cell lung cancer treated with pembrolizumab. After two cycles, he developed new-onset dyspnoea on exertion. Electrocardiogram showed idioventricular rhythm with diffuse ST-segment elevations. Echocardiography revealed severe biventricular cardiac dysfunction. Based on diagnostic workup and exclusion of probable aetiologies, the patient was diagnosed with pembrolizumab-induced myocarditis. The treatment was initiated with corticosteroids and guideline-conform heart failure therapy. He demonstrated a marked clinical response with resolution of congestive heart failure symptoms. This article summarises the clinical evidence regarding the epidemiology, pathophysiology, clinical features, diagnostic modalities and management of patients with pembrolizumab-associated myocarditis. In addition, it highlights that programmed death receptor-1 inhibition can cause a spectrum of autoimmune adverse events requiring clinical monitoring and periodic screenings. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Exploring barriers and facilitators to the clinical use of virtual reality for post-stroke unilateral spatial neglect assessment.

PubMed

Ogourtsova, Tatiana; Archambault, Philippe S; Lamontagne, Anouk

2017-11-07

Hemineglect, defined as a failure to attend to the contralesional side of space, is a prevalent and disabling post-stroke deficit. Conventional hemineglect assessments lack sensitivity as they contain mainly non-functional tasks performed in near-extrapersonal space, using static, two-dimensional methods. This is of concern given that hemineglect is a strong predictor for functional deterioration, limited post-stroke recovery, and difficulty in community reintegration. With the emerging field of virtual reality, several virtual tools have been proposed and have reported better sensitivity in neglect-related deficits detection than conventional methods. However, these and future virtual reality-based tools are yet to be implemented in clinical practice. The present study aimed to explore the barriers/facilitators perceived by clinicians in the use of virtual reality for hemineglect assessment; and to identify features of an optimal virtual assessment. A qualitative descriptive process, in the form of focus groups, self-administered questionnaire and individual interviews was used. Two focus groups (n = 11 clinicians) were conducted and experts in the field (n = 3) were individually interviewed. Several barriers and facilitators, including personal, institutional, client suitability, and equipment factors, were identified. Clinicians and experts in the field reported numerous features for the virtual tool optimization. Factors identified through this study lay the foundation for the development of a knowledge translation initiative towards an implementation of a virtual assessment for hemineglect. Addressing the identified barriers/facilitators during implementation and incorporating the optimal features in the design of the virtual assessment could assist and promote its eventual adoption in clinical settings. Implications for rehabilitation A multimodal and active knowledge translation intervention built on the presently identified modifiable factors is suggested to be implemented to support the clinical integration of a virtual reality-based assessment for post-stroke hemineglect. To amplify application and usefulness of a virtual-reality based tool in the assessment of post-stroke hemineglect, optimal features identified in the present study should be incorporated in the design of such technology.

Neuroradiology Using Secure Mobile Device Review.

PubMed

Randhawa, Privia A; Morrish, William; Lysack, John T; Hu, William; Goyal, Mayank; Hill, Michael D

2016-04-05

Image review on computer-based workstations has made film-based review outdated. Despite advances in technology, the lack of portability of digital workstations creates an inherent disadvantage. As such, we sought to determine if the quality of image review on a handheld device is adequate for routine clinical use. Six CT/CTA cases and six MR/MRA cases were independently reviewed by three neuroradiologists in varying environments: high and low ambient light using a handheld device and on a traditional imaging workstation in ideal conditions. On first review (using a handheld device in high ambient light), a preliminary diagnosis for each case was made. Upon changes in review conditions, neuroradiologists were asked if any additional features were seen that changed their initial diagnoses. Reviewers were also asked to comment on overall clinical quality and if the handheld display was of acceptable quality for image review. After the initial CT review in high ambient light, additional findings were reported in 2 of 18 instances on subsequent reviews. Similarly, additional findings were identified in 4 of 18 instances after the initial MR review in high ambient lighting. Only one of these six additional findings contributed to the diagnosis made on the initial preliminary review. Use of a handheld device for image review is of adequate diagnostic quality based on image contrast, sharpness of structures, visible artefacts and overall display quality. Although reviewers were comfortable with using this technology, a handheld device with a larger screen may be diagnostically superior.

Mother-child interactions in young children with excessive physical aggression and in typically developing young children.

PubMed

Urbain-Gauthier, Nadine; Wendland, Jaqueline

2017-07-01

Among the multiple risk factors, the emergence of conduct problems in young children may be linked to harsh parenting and child's temperamental difficulties, leading to a reciprocal early discordant relationship. Little is known about the characteristics of early parent-child interactions in young children with physical aggression. The purpose of the current study was to evaluate the characteristics of mother-child interactions in dyads referred for excessive physical aggression in young children under 5 years of age compared to mother-child interactions in typically developing young children. Mother-child interactions were assessed during a free-play session in both a clinical sample ( N = 70, child mean age  = 3.5 years) and a nonclinical sample ( N = 80, child mean age  = 3.5 years) by using the Rating Scale of Interaction Style (Clark and Seifer, adapted by Molitor and Mayes). Significant differences were found between several interactive features in clinical and nonclinical dyads. In clinical dyads, mothers' behaviors were often characterized by intrusiveness and criticism toward children, and poor facilitative positioning. Children with excessive aggressive behavior often displayed poor communication, initiation of bids, and poor responsiveness toward the mother. They displayed fewer sustained bouts of play than typically developing children did. In clinical dyads, strong positive correlations were found between child responsiveness and maternal interest in engagement ( r = .41, p < .001), while the child displaying sustained bouts of play was negatively correlated with the mother's attempts to intrude on the child's activity ( r = .64, p < .05). These data show that children with excessive aggressive behavior develop disrupted mother-infant interactions from a very young age. Several negative interactive features and correlations between child behavior and maternal behavior were found in clinical samples. The effects of these features add up and probably strengthen each other, thus leading to interactive difficulties from a very young age. More attention should be paid to early parent-child interactions in case of child behavioral problems. The recognition of these interactive dysfunctions is discussed in terms of clinical implications for therapeutic interventions.

SU-F-T-100: Development and Implementation of a Treatment Planning Tracking System Into the Radiation Oncology Clinic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabat, C; Cline, K; Li, Y

Purpose: With increasing numbers of cancer patients being diagnosed and the complexity of radiotherapy treatments rising it’s paramount that patient plan development continues to stay fluid within the clinic. In order to maintain a high standard of care and clinical efficiency the establishment of a tracking system for patient plan development allows healthcare providers to view real time plan progression and drive clinical workflow. In addition, it provides statistical datasets which can further identify inefficiencies within the clinic. Methods: An application was developed utilizing Microsoft’s ODBC SQL database engine to track patient plan status throughout the treatment planning process whilemore » also managing key factors pertaining to the patient’s treatment. Pertinent information is accessible to staff in many locations, including tracking monitors within dosimetry, the clinic network for both computers and handheld devices, and through email notifications. Plans are initiated with a CT and continually tracked through planning stages until final approval by staff. Patient’s status is dynamically updated by the physicians, dosimetrists, and medical physicists based on the stage of the patient’s plan. Results: Our application has been running over a six month period with all patients being processed through the system. Modifications have been made to allow for new features to be implemented along with additional tracking parameters. Based on in-house feedback, the application has been supportive in streamlining patient plans through the treatment planning process and data has been accumulating to further improve procedures within the clinic. Conclusion: Over time the clinic will continue to track data with this application. As data accumulates the clinic will be able to highlight inefficiencies within the workflow and adapt accordingly. We will add in new features to help support the treatment planning process in the future.« less

Characterization of hypertriglyceridemia and response to treatment with insulin in llamas and alpacas: 31 cases (1995-2005).

PubMed

Waitt, Laura H; Cebra, Christopher K

2008-05-01

To evaluate camelids with hypertriglyceridemia with regard to signalment, clinical features of disease, and response to treatment with insulin. Retrospective case series. 23 alpacas and 8 llamas with hypertriglyceridemia. For analysis of medical record data, 20 hypertriglyceridemic camelids with multiple recorded measurements of serum or plasma triglycerides concentration were classified as follows: those with an initial triglycerides concentration > 60 to > or = 500 mg/dL that were or were not treated with insulin (HT-I and HT-N camelids, respectively) and those with an initial triglycerides concentration > 500 mg/dL that were treated with insulin (lipemic [LIP-I] camelids). Only 1 recorded triglycerides concentration was available for an additional 11 hypertriglyceridemic camelids; data from those records were included in the characterization of signalment and clinical features of disease. Compared with the general population of hospitalized camelids, hypertriglyceridemic camelids did not differ significantly with respect to age or sex. Of 22 female camelids, only 7 were lactating or pregnant. Serum or plasma triglycerides concentrations in HT-N and HT-I camelids did not differ significantly at admission, but triglycerides concentrations in HT-I camelids decreased significantly after insulin treatment. Posttreatment triglycerides concentrations in HT-I camelids were significantly lower than those in HT-N camelids. During the period of hospitalization, triglycerides concentrations in HT-N camelids increased, whereas those in LIP-I camelids decreased significantly. Results indicated that hypertriglyceridemia affects llamas and alpacas of all ages and both sexes. Insulin treatment may reduce serum or plasma triglycerides concentrations in camelids with hypertriglyceridemia.

The impact of insight in a first-episode mania with psychosis population on outcome at 18 months.

PubMed

Smith, Leo T; Shelton, Clare L; Berk, Michael; Hasty, Melissa K; Cotton, Sue M; Henry, Lisa; Daglas, Rothanthi; Gentle, Ellen; McGorry, Patrick D; Macneil, Craig A; Conus, Philippe

2014-01-01

To explore whether poor initial insight during a first episode of mania with psychotic features was predictive of poor psychosocial and clinical outcomes at 18 months. Secondary analysis was performed on data collected during an 8-week RCT comparing the efficacy of olanzapine versus chlorpromazine as an adjunct to lithium, and at 18-month follow-up. 74 participants were divided into three groups (no insight, partial insight, and full insight) according to the insight item from the Young Mania Rating Scale (YMRS). Differences between these three groups were examined at baseline and at 18 months on measures of symptoms (YMRS, HAMD-21, and CGI-S), and social and occupational functioning (SOFAS). Baseline differences between the three groups were determined using general linear models and chi-squared analyses. Group differences from baseline to 18-month follow-up were determined using repeated measures general linear models. At baseline there were significant differences between the three insight groups in terms of mania and functioning, but at 18 months all groups had improved significantly in terms of psychopathology, mania, depression and social and occupational functioning. There were no significant differences between the three groups at study completion with respect to these domains. The study was limited by the lack of availability of a more detailed rating scale for insight, and it did not account for the duration of untreated psychosis (DUI). Poor initial insight during a first episode of mania with psychotic features does not predict poor clinical and psychosocial outcome at 18 months. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Idiopathic hypersomnia: clinical features and response to treatment.

PubMed

Ali, Mohsin; Auger, R Robert; Slocumb, Nancy L; Morgenthaler, Timothy I

2009-12-15

A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. A retrospective review of our database initially identified 997 patients, utilizing "idiopathic hypersomnia", "hypersomnia NOS", and "primary hypersomnia" as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a "complete response" to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of "complete" or "partial" responses than modafinil, although statistical significance was not reached (38/40 [95%] vs. 22/25 [88%], respectively, p = 0.291). The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored.

Primary anaplastic pilocytic astrocytoma.

PubMed

Azad, A; Deb, S; Cher, L

2009-12-01

We report two adult patients with pilocytic astrocytomas with anaplastic features at initial diagnosis. Pilocytic astrocytomas are low-grade astrocytomas that occur rarely in adults. Initial presentation of a pilocytic astrocytoma with anaplastic features is particularly uncommon and making a definitive diagnosis of pilocytic astrocytoma with anaplastic features can be challenging. It is critical to differentiate glioblastoma (World Health Organization [WHO] grade 4) and pilocytic astrocytoma with anaplastic features (WHO grade 3) from pilocytic astrocytoma (WHO grade 1) as there are significant therapeutic and prognostic implications. Improved therapeutic strategies are required for pilocytic astrocytomas with anaplastic features.

Tuberculosis in Pap samples with emphasis on LBC: Caught only when thought.

PubMed

Bharani, Vani; Gupta, Nalini; Suri, Vanita; Rajwanshi, Arvind

2018-05-01

Despite being a commonly encountered infection, the clinical diagnosis of tuberculosis of the uterine cervix is elusive. Though a straightforward diagnosis on tissue sections, identification of typical features of tubercular infection on cervical Pap samples is challenging. In our experience, the infrequent pale staining collections of epithelioid cells are difficult to pick up on Pap stained smears, particularly LBC samples. In this series, 2 of the three samples were reported as atypical squamous cells of undetermined significance while 1 was reported as inflammatory at the initial diagnosis. Scattered Langhans' type giant cells may be seen as a subtle clue which should prompt the search for epithelioid cell granulomas. These cases may have a mass lesion clinically while no obvious signs of malignancy on the cervical samples. © 2017 Wiley Periodicals, Inc.

[Thrombotic microangiopathy].

PubMed

Beutel, G; Kielstein, J T; Ganser, A

2013-09-01

Thrombotic microangiopathy should be suspected every time the combination of microangiopathic hemolytic anemia without a coexisting cause, thrombocytopenia as well as renal and/or neurologic abnormalities occurs. The general term thrombotic microangiopathy includes different subtypes of the disease leading to abnormalities in multiple organ systems by endothelial injury and formation of platelet-rich thrombi in small vessels. The main types include thrombotic thrombocytopenic purpura in case of dominant neurologic abnormalities and the hemolytic uremic syndrome in case of acute kidney injury, respectively. Although these syndromes differ in their etiologies, clinical features, response to treatment, and prognosis, an early initiation of a direct therapeutic intervention frequently determines the clinical course of the patient. Irrespectively of the underlying etiology, plasma exchange is an essential component of acute therapeutic intervention while ongoing diagnostics are used to identify the definite treatment.

Cholecystitis and nephrotic syndrome complicating Epstein-Barr virus primary infection.

PubMed

Rodà, Diana; Huici, Malka; Ricart, Sílvia; Vila, Jordi; Fortuny, Clàudia; Alsina, Laia

2017-02-01

Epstein-Barr virus (EBV) infection results in a spectrum of clinical manifestations. The host immune response to EBV plays a key role in the extent and degree of clinical features, which in children under 4 years of age are usually mild, non-specific and self-limiting. A 2-year-old boy in whom no known immune disorder could be found presented with acute acalculous cholecystitis, renal dysfunction with massive proteinuria, ascites, pleural effusion, minimal peripheral oedema and a severe systemic inflammatory response. Improvement occurred after initiation of corticosteroids and antiviral treatment with gancyclovir. In severely symptomatic or complicated EBV infection, a primary immunodeficiency must be suspected. If a primary immunodeficiency has been ruled out, the correct management of severe EBV infection in the immunocompetent host remains controversial.

United Kingdom immune thrombocytopenia registry: retrospective evaluation of bone marrow fibrosis in adult patients with primary immune thrombocytopenia and correlation with clinical findings.

PubMed

Rizvi, Hasan; Butler, Tom; Calaminici, Mariarita; Doobaree, Indraraj U; Nandigam, Raghava C; Bennett, Dimitri; Provan, Drew; Newland, Adrian C

2015-05-01

Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with thrombopoietin receptor agonists (TPO-RA). However, fibrosis has also been reported in patients with various stages of ITP, who were TPO-RA treatment-naïve. In our study, we looked for fibrosis in bone marrow trephine biopsies taken at initial diagnosis from 32 adult patients with ITP. Ten of the 32 evaluated samples (31·25%) showed increased reticulin (Grade 1-2 on Bauermeister scale and Grade 0-1 on the European Consensus scale), which showed a positive correlation with ethnicity (0·3%) but did not correlate with disease severity, any clinical features or co-morbidities. © 2015 John Wiley & Sons Ltd.

Biological features of hepatitis B virus isolates from patients based on full-length genomic analysis.

PubMed

Wen, Yu-Mei; Wang, Yong-Xiang

2009-01-01

The mechanisms for HBV persistence and the pathogenesis of chronic HB have been shown mainly due to defects in host immune responses. However, HBV isolates with different biological features may also contribute to different clinical outcomes and epidemiological implications in viral hepatitis B (HB). This review presents interesting biological features of HBV isolates based on the structural and functional analysis of full-length HBV isolates from various patients. Among isolates from children after failure of HB vaccination, 129L mutant at the 'a' determinant was found with normal binding efficiency to anti-HBs, but with reduced immunogenicity, which could initiate persistent HBV infections. Isolates from fulminant hepatitis (FH) B patients were not all highly replicative, but differences in capacities of anti-HBs induction could be involved in the pathogenesis of FH. The high replicative competency of isolates from hepatocellular carcinoma (HCC) patients could result in enhanced immune-mediated cytopathic effects against HBV viral proteins, and increased transactivating activity by the X protein. The mechanism of a double-spliced variant in enhancing replication of the wild-type virus is presented. The importance of integrating structural and functional analysis to reveal biological features of HBV isolates in viral pathogenesis is discussed.

Unclear-onset intracerebral hemorrhage: Clinical characteristics, hematoma features, and outcomes.

PubMed

Inoue, Yasuteru; Miyashita, Fumio; Koga, Masatoshi; Minematsu, Kazuo; Toyoda, Kazunori

2017-12-01

Background and purpose Although unclear-onset ischemic stroke, including wake-up ischemic stroke, is drawing attention as a potential target for reperfusion therapy, acute unclear-onset intracerebral hemorrhage has been understudied. Clinical characteristics, hematoma features, and outcomes of patients who developed intracerebral hemorrhage during sleep or those with intracerebral hemorrhage who were unconscious when witnessed were determined. Methods Consecutive intracerebral hemorrhage patients admitted within 24 hours after onset or last-known normal time were classified into clear-onset intracerebral hemorrhage and unclear-onset intracerebral hemorrhage groups. Outcomes included initial hematoma volume, initial National Institutes of Health Stroke Scale score, hematoma growth on 24-hour follow-up computed tomography, and vital and functional prognoses at 30 days. Results Of 377 studied patients (122 women, 69 ± 11 years old), 147 (39.0%) had unclear-onset intracerebral hemorrhage. Patients with unclear-onset intracerebral hemorrhage had larger hematoma volumes (p = 0.044) and higher National Institutes of Health Stroke Scale scores (p < 0.001) than those with clear-onset intracerebral hemorrhage after multivariable adjustment for risk factors and comorbidities. Hematoma growth was similarly common between the two groups (p = 0.176). There were fewer patients with modified Rankin Scale (mRS) scores of 0-2 (p = 0.033) and more patients with mRS scores of 5-6 (p = 0.009) and with fatal outcomes (p = 0.049) in unclear-onset intracerebral hemorrhage group compared with clear-onset intracerebral hemorrhage as crude values, but not after adjustment. Conclusions Patients with unclear-onset intracerebral hemorrhage presented with larger hematomas and higher National Institutes of Health Stroke Scale scores at emergent visits than those with clear-onset intracerebral hemorrhage, independent of underlying characteristics. Unclear-onset intracerebral hemorrhage patients showed poorer 30-day vital and functional outcomes than clear-onset intracerebral hemorrhage patients; these differences seem to be mainly due to initial hematoma volumes and National Institutes of Health Stroke Scale scores.

Pencil beam characteristics of the next-generation proton scanning gantry of PSI: design issues and initial commissioning results

NASA Astrophysics Data System (ADS)

Pedroni, E.; Meer, D.; Bula, C.; Safai, S.; Zenklusen, S.

2011-07-01

In this paper we report on the main design features, on the realization process and on selected first results of the initial commissioning of the new Gantry 2 of PSI for the delivery of proton therapy with new advanced pencil beam scanning techniques. We present briefly the characteristics of the new gantry system with main emphasis on the beam optics, on the characterization of the pencil beam used for scanning and on the performance of the scanning system. The idea is to give an overview of the major components of the whole system. The main long-term technical goal of the new equipment of Gantry 2 is to expand the use of pencil beam scanning to the whole spectrum of clinical indications including moving targets. We report here on the initial experience and problems encountered in the development of the system with selected preliminary results of the ongoing commissioning of Gantry 2.

ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling

PubMed Central

Goossens, Steven; Radaelli, Enrico; Blanchet, Odile; Durinck, Kaat; Van der Meulen, Joni; Peirs, Sofie; Taghon, Tom; Tremblay, Cedric S.; Costa, Magdaline; Ghahremani, Morvarid Farhang; De Medts, Jelle; Bartunkova, Sonia; Haigh, Katharina; Schwab, Claire; Farla, Natalie; Pieters, Tim; Matthijssens, Filip; Van Roy, Nadine; Best, J. Adam; Deswarte, Kim; Bogaert, Pieter; Carmichael, Catherine; Rickard, Adam; Suryani, Santi; Bracken, Lauryn S.; Alserihi, Raed; Canté-Barrett, Kirsten; Haenebalcke, Lieven; Clappier, Emmanuelle; Rondou, Pieter; Slowicka, Karolina; Huylebroeck, Danny; Goldrath, Ananda W.; Janzen, Viktor; McCormack, Matthew P.; Lock, Richard B.; Curtis, David J.; Harrison, Christine; Berx, Geert; Speleman, Frank; Meijerink, Jules P. P.; Soulier, Jean; Van Vlierberghe, Pieter; Haigh, Jody J.

2015-01-01

Early T-cell precursor leukaemia (ETP-ALL) is a high-risk subtype of human leukaemia that is poorly understood at the molecular level. Here we report translocations targeting the zinc finger E-box-binding transcription factor ZEB2 as a recurrent genetic lesion in immature/ETP-ALL. Using a conditional gain-of-function mouse model, we demonstrate that sustained Zeb2 expression initiates T-cell leukaemia. Moreover, Zeb2-driven mouse leukaemia exhibit some features of the human immature/ETP-ALL gene expression signature, as well as an enhanced leukaemia-initiation potential and activated Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signalling through transcriptional activation of IL7R. This study reveals ZEB2 as an oncogene in the biology of immature/ETP-ALL and paves the way towards pre-clinical studies of novel compounds for the treatment of this aggressive subtype of human T-ALL using our Zeb2-driven mouse model. PMID:25565005

ClinicalTrials.gov Turns 10! | NIH MedlinePlus the Magazine

MedlinePlus

... please turn Javascript on. Feature: Clinical Trials ClinicalTrials.gov Turns 10! Past Issues / Fall 2010 Table of ... and whom to contact for more information. ClinicalTrials.gov's Helpful Features ClinicalTrials.gov has many helpful consumer ...

Misdiagnosis of cerebellar hemorrhage - features of 'pseudo-gastroenteritis' clinical presentations to the ED and primary care.

PubMed

Lee, Seung-Han; Stanton, Victoria; Rothman, Richard E; Crain, Barbara; Wityk, Robert; Wang, Zheyu; Newman-Toker, David E

2017-03-01

Early-stage cerebellar hemorrhage can present with nausea or vomiting absent other neurological symptoms or signs, potentially leading to an incorrect diagnosis of gastroenteritis. We sought to determine the frequency of gastroenteritis-like presentations and delayed or missed diagnoses among patients with spontaneous cerebellar hemorrhage. This is a retrospective, case-control analysis of atraumatic, primary cerebellar hemorrhages derived from a systematic search of surgical pathology and autopsy databases at two large urban, academic medical centers from 1984 to 2006. Hospital visit and clinical symptom data were abstracted from electronic and paper medical records for included patients. Delayed or missed diagnoses were defined as those at least one previous visit for relevant clinical symptoms in the 7 days prior to the correct diagnosis being confirmed. Among 254 records captured by our search filter, we identified 35 cases of pathologically proven primary cerebellar hemorrhage. Four patients (11%) were misdiagnosed initially - three with "gastroenteritis" and one with "hypertension". In this small sample, misdiagnosed patients presented more often with normal mental state (100% vs. 35%, p=0.07) and nausea/vomiting (100% vs. 58%, p=0.22). Although patients deteriorated clinically after the initial misdiagnosis, and potentially dangerous diagnostic tests and treatment strategies were instituted as a result of misdiagnosis, none of the misdiagnosed patients died or suffered major permanent harms due to diagnostic delay. Our study is limited by the small number of identified cases. Nevertheless, it appears that patients with cerebellar hemorrhages can present with relatively unimpressive clinical findings without obvious neurological manifestations. Such individuals are sometimes misdiagnosed with gastroenteritis or other benign disorders initially, possibly when neurologic examination, particularly gait testing, is omitted or abridged. A careful search for subtle cerebellar signs, including dysarthria, limb ataxia, nystagmus or tandem gait instability, absent in true gastroenteritis cases, could potentially reduce misdiagnosis.

TU-CD-BRB-01: Normal Lung CT Texture Features Improve Predictive Models for Radiation Pneumonitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krafft, S; The University of Texas Graduate School of Biomedical Sciences, Houston, TX; Briere, T

2015-06-15

Purpose: Existing normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) traditionally rely on dosimetric and clinical data but are limited in terms of performance and generalizability. Extraction of pre-treatment image features provides a potential new category of data that can improve NTCP models for RP. We consider quantitative measures of total lung CT intensity and texture in a framework for prediction of RP. Methods: Available clinical and dosimetric data was collected for 198 NSCLC patients treated with definitive radiotherapy. Intensity- and texture-based image features were extracted from the T50 phase of the 4D-CT acquired for treatment planning. Amore » total of 3888 features (15 clinical, 175 dosimetric, and 3698 image features) were gathered and considered candidate predictors for modeling of RP grade≥3. A baseline logistic regression model with mean lung dose (MLD) was first considered. Additionally, a least absolute shrinkage and selection operator (LASSO) logistic regression was applied to the set of clinical and dosimetric features, and subsequently to the full set of clinical, dosimetric, and image features. Model performance was assessed by comparing area under the curve (AUC). Results: A simple logistic fit of MLD was an inadequate model of the data (AUC∼0.5). Including clinical and dosimetric parameters within the framework of the LASSO resulted in improved performance (AUC=0.648). Analysis of the full cohort of clinical, dosimetric, and image features provided further and significant improvement in model performance (AUC=0.727). Conclusions: To achieve significant gains in predictive modeling of RP, new categories of data should be considered in addition to clinical and dosimetric features. We have successfully incorporated CT image features into a framework for modeling RP and have demonstrated improved predictive performance. Validation and further investigation of CT image features in the context of RP NTCP modeling is warranted. This work was supported by the Rosalie B. Hite Fellowship in Cancer research awarded to SPK.« less

Knowing where is different from knowing what: Distinct response time profiles and accuracy effects for target location, orientation, and color probability.

PubMed

Jabar, Syaheed B; Filipowicz, Alex; Anderson, Britt

2017-11-01

When a location is cued, targets appearing at that location are detected more quickly. When a target feature is cued, targets bearing that feature are detected more quickly. These attentional cueing effects are only superficially similar. More detailed analyses find distinct temporal and accuracy profiles for the two different types of cues. This pattern parallels work with probability manipulations, where both feature and spatial probability are known to affect detection accuracy and reaction times. However, little has been done by way of comparing these effects. Are probability manipulations on space and features distinct? In a series of five experiments, we systematically varied spatial probability and feature probability along two dimensions (orientation or color). In addition, we decomposed response times into initiation and movement components. Targets appearing at the probable location were reported more quickly and more accurately regardless of whether the report was based on orientation or color. On the other hand, when either color probability or orientation probability was manipulated, response time and accuracy improvements were specific for that probable feature dimension. Decomposition of the response time benefits demonstrated that spatial probability only affected initiation times, whereas manipulations of feature probability affected both initiation and movement times. As detection was made more difficult, the two effects further diverged, with spatial probability disproportionally affecting initiation times and feature probability disproportionately affecting accuracy. In conclusion, all manipulations of probability, whether spatial or featural, affect detection. However, only feature probability affects perceptual precision, and precision effects are specific to the probable attribute.

Survey of Current Practice in the Fitting and Fine-Tuning of Common Signal-Processing Features in Hearing Aids for Adults.

PubMed

Anderson, Melinda C; Arehart, Kathryn H; Souza, Pamela E

2018-02-01

Current guidelines for adult hearing aid fittings recommend the use of a prescriptive fitting rationale with real-ear verification that considers the audiogram for the determination of frequency-specific gain and ratios for wide dynamic range compression. However, the guidelines lack recommendations for how other common signal-processing features (e.g., noise reduction, frequency lowering, directional microphones) should be considered during the provision of hearing aid fittings and fine-tunings for adult patients. The purpose of this survey was to identify how audiologists make clinical decisions regarding common signal-processing features for hearing aid provision in adults. An online survey was sent to audiologists across the United States. The 22 survey questions addressed four primary topics including demographics of the responding audiologists, factors affecting selection of hearing aid devices, the approaches used in the fitting of signal-processing features, and the strategies used in the fine-tuning of these features. A total of 251 audiologists who provide hearing aid fittings to adults completed the electronically distributed survey. The respondents worked in a variety of settings including private practice, physician offices, university clinics, and hospitals/medical centers. Data analysis was based on a qualitative analysis of the question responses. The survey results for each of the four topic areas (demographics, device selection, hearing aid fitting, and hearing aid fine-tuning) are summarized descriptively. Survey responses indicate that audiologists vary in the procedures they use in fitting and fine-tuning based on the specific feature, such that the approaches used for the fitting of frequency-specific gain differ from other types of features (i.e., compression time constants, frequency lowering parameters, noise reduction strength, directional microphones, feedback management). Audiologists commonly rely on prescriptive fitting formulas and probe microphone measures for the fitting of frequency-specific gain and rely on manufacturers' default settings and recommendations for both the initial fitting and the fine-tuning of signal-processing features other than frequency-specific gain. The survey results are consistent with a lack of published protocols and guidelines for fitting and adjusting signal-processing features beyond frequency-specific gain. To streamline current practice, a transparent evidence-based tool that enables clinicians to prescribe the setting of other features from individual patient characteristics would be desirable. American Academy of Audiology

Clinico-morphological features of BRAF inhibition-induced proliferative skin lesions in cancer patients.

PubMed

Belum, Viswanath Reddy; Rosen, Alyx C; Jaimes, Natalia; Dranitsaris, George; Pulitzer, Melissa P; Busam, Klaus J; Marghoob, Ashfaq A; Carvajal, Richard D; Chapman, Paul B; Lacouture, Mario E

2015-01-01

The use of BRAF inhibitors may lead to the development of cutaneous toxicities such as rashes, photosensitivity, alopecia, palmoplantar erythrodysesthesia, and proliferative skin lesions, including keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs). The latter are noteworthy for their potential to exhibit malignant features, and they may necessitate invasive treatment. Their prompt identification is of primary importance for directing supportive care efforts and maintaining dose intensity while minimizing the morbidity associated with supportive care interventions. Because such lesions are less familiar to oncologists, this study was designed to characterize their clinico-morphological features, which have not been hitherto described. The clinical and dermoscopic characteristics and risk factors of new-onset proliferative skin lesions (benign verrucous lesions and KAs/cuSCCs) developing after the initiation of treatment with vemurafenib, dabrafenib, and XL281 were analyzed; the histopathological diagnoses were ascertained. The majority of the lesions were benign verrucous lesions (78%, n = 87), whereas KAs/cuSCCs represented 22% (n = 25). The median times to biopsy for the initial verrucous lesions and KAs/cuSCCs were 4.8 and 10.5 weeks, respectively. The clinico-morphological features significant for KAs/cuSCCs included a larger size (P < .001), a nodular appearance (P < .001), a central keratin plug (P < .001), a central ulceration or crust (P = .04), an adherent scale (P = .02), an erythematous halo (P = .03), and a scaly ring (collarette; P < .001) at the periphery. Our findings represent the first detailed description of the clinico-morphological characteristics that permit distinction between the benign and malignant skin lesions induced by BRAF inhibitors. They are valuable for the recognition of lesions that require intervention and/or a dermatology referral versus those that permit provisional monitoring. © 2014 American Cancer Society.

Update on risk stratification and treatment of newly diagnosed multiple myeloma.

PubMed

Kapoor, Prashant; Rajkumar, S Vincent

2011-10-01

Multiple myeloma is the second most common hematologic malignancy. Chromosomal aberrations are important prognostic determinants that influence the clinical decision-making in newly-diagnosed multiple myeloma (NDMM). Patients are considered high-risk if any of the following features are detected: hypodiploidy, deletion 13 by cytogenetics, t(4;14), t(14;16), t(14;20) and/or 17 p deletion. In the absence of these features patients are considered standard risk. Outside of trials, risk-adapted therapy in the transplant-eligible high-risk patients advocates use of bortezomib-based induction therapy followed by autologous stem cell transplantation (ASCT) and bortezomib-based maintenance therapy. High-risk, transplant-ineligible patients should also utilize bortezomib as initial therapy since it is known to overcome the poor prognosis associated with some high-risk features. The goal of therapy in high-risk patients is to attain and maintain a state of complete remission as much as possible. In contrast, the standard-risk, transplant-eligible patients may be treated with either lenalidomide-dexamethasone or bortezomib-based therapy followed by ASCT. In such patients, ASCT can also be deferred until first relapse if the patients are tolerating initial therapy well. Lenalidomide maintenance therapy in the post-transplant setting in standard-risk patients is controversial and not recommended routinely. For transplant-ineligible standard-risk patients, multiple options exist, although in the absence direct comparisons, we prefer lenalidomide plus low-dose dexamethasone over melphalan-based combinations. This review outlines evidence-based management approaches in NDMM, with a focus on risk-adapted therapy.

Comparison of clinical features and 3-month treatment response among three different choroidal thickness groups in polypoidal choroidal vasculopathy.

PubMed

Kong, Mingui; Kim, Sung Min; Ham, Don-Il

2017-01-01

Eyes with polypoidal choroidal vasculopathy (PCV) were recently reported to have various choroidal thickness, and choroidal thickness might be associated with visual outcome in the treatment of many retinal disorders. The range of subfoveal choroidal thickness (SFCT), clinical features, and 3-month treatment response among three groups having different range of SFCT were investigated in PCV eyes. In 78 treatment-naïve eyes with PCV, SFCT was measured using optical coherence tomography. Eyes were classified into thin, medium, and thick groups, using mean and one standard deviation of SFCT. Clinical features and imaging findings were compared among the three groups. Some eyes were treated with three consecutive monthly injection of anti-vascular endothelial growth factor (VEGF) as an initial treatment. They were also classified into three thickness groups, and the short-term post-treatment improvement in visual acuity and central retinal thickness were compared among groups. The mean SFCT was 271.9 ± 135.6 μm. Twelve, 53, and 13 eyes were classified into thin (<136.3 μm), medium (136.3-407.5 μm), and thick (>407.5 μm) groups, respectively. The thin group showed older age, lower visual acuity, and a higher prevalence of fundus tessellation than the other two groups (P <0.05). In multiple linear regression analyses, baseline BCVA was correlated with baseline SFCT. Forty-six eyes completed three consecutive anti-VEGF treatments. The thin group showed no visual improvement after treatment (P = 0.141), unlike the other two groups showing visual improvement (P<0.05). Eyes with PCV have a broad range of SFCT, and PCV eyes with a thin choroid manifest worse visual function than eyes with a medium or thick choroid.

Clinicopathologic features of adult T-cell leukemias/lymphomas at a North American tertiary care medical center: infrequent involvement of the central nervous system.

PubMed

Hsi, Andy C; Kreisel, Friederike H; Frater, John L; Nguyen, TuDung T

2014-02-01

Human T-cell lymphotropic virus type 1 is associated with adult T-cell leukemia/lymphoma (ATLL). Published series of ATLLs seen at a United States medical institution are rare. We present the features of 4 ATLLs diagnosed at our North American tertiary care medical center from 1990 to 2012. Despite the absence of a history of origin from an endemic region, all our ATLLs demonstrated evidence of human T-cell lymphotropic virus type 1 infection. Central nervous system (CNS) involvement by ATLL was uncommon in our series, and represented only 1.6% (1/64) of all CNS B-cell or T-cell lymphomas diagnosed over a 20+ year period at our institution. Review of the medical literature reveals that the majority of CNS-involved ATLLs present with the lymphoma or acute subtype, and complete remission is difficult to achieve in these cases. CNS involvement frequently occurs with a systemic disease, which carries an aggressive clinical course with poor prognosis. In addition, CNS involvement by ATLL can be the initial presentation or seen with relapsed disease, can be the only site or be associated with other tissue sites of involvement, and may manifest with variable clinical signs/symptoms. Our retrospective study reveals that ATLLs are rare mature T-cell lymphomas in a native North American population, but the clinical and histopathologic features of ATLLs from this nonendemic region are similar to those seen from other endemic regions. Early recognition of these rare ATLLs involving uncommon sites, such as the CNS, will help optimize treatment for these infrequent mature T-cell lymphomas.

Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma receiving external beam radiotherapy.

PubMed

He, Jian; Zeng, Zhao-Chong; Tang, Zhao-You; Fan, Jia; Zhou, Jian; Zeng, Meng-Su; Wang, Jian-Hua; Sun, Jing; Chen, Bing; Yang, Ping; Pan, Bai-Sheng

2009-06-15

The current study was performed to identify clinical features and independent predictors of survival in patients with bone metastases from hepatocellular carcinoma (HCC). Patients (n = 205) with bone metastases from HCC received external beam radiotherapy (EBRT) between 1997 and 2007. Demographic variables, laboratory values, tumor characteristics, and treatment modalities were determined before EBRT. The total radiation dose ranged from 32 to 66 grays (Gy) (median, 50 Gy) and was focused on the involved bone. In 80 of 205 (39.0%) patients with bone metastasis from HCC, tumors were characterized by osteolytic, expansile soft-tissue masses. Overall pain relief from EBRT occurred in 204 patients (99.5%). No consistent dose-response relation was found for palliation of bone metastases with doses between 32 and 66 Gy (P = .068), but the retreatment rate was higher in patients with expansile soft tissue. On univariate analysis, shorter survival was associated with poorer Karnofsky performance status (KPS), higher gamma-glutamyltransferase and alpha-fetoprotein levels, tumor size >5 cm, uncontrolled intrahepatic tumors, multifocal bone lesions, involvement of spinal vertebrae, extraosseous metastases, and a shorter disease-free interval after an initial diagnosis of HCC. On multivariate analysis, pretreatment-unfavorable predictors were associated with lower KPS, higher tumor markers, and uncontrolled intrahepatic tumor when KPS was considered. The median survival was 7.4 months. The results of the current study provide detailed information regarding clinical features, survival outcomes, and prognostic factors for HCC with bone metastases in a relatively large cohort of patients treated with EBRT. These prognostic factors will help in determining which dose and fraction are appropriate. (c) 2009 American Cancer Society.

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review

PubMed Central

Watanabe, Junko; Togo, Shinsaku; Sumiyoshi, Issei; Namba, Yukiko; Suina, Kentaro; Mizuno, Takafumi; Kadoya, Kotaro; Motomura, Hiroaki; Iwai, Moe; Nagaoka, Tetsutaro; Sasaki, Shinichi; Hayashi, Takuo; Uekusa, Toshimasa; Abe, Kanae; Urata, Yasuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Kato, Shunsuke; Takahashi, Kazuhisa

2018-01-01

Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement (p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC (p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome. PMID:29844868

Iatrogenic occlusion of the ophthalmic artery after cosmetic facial filler injections: a national survey by the Korean Retina Society.

PubMed

Park, Kyu Hyung; Kim, Yong-Kyu; Woo, Se Joon; Kang, Se Woong; Lee, Won Ki; Choi, Kyung Seek; Kwak, Hyung Woo; Yoon, Ill Han; Huh, Kuhl; Kim, Jong Woo

2014-06-01

Iatrogenic occlusion of the ophthalmic artery and its branches is a rare but devastating complication of cosmetic facial filler injections. To investigate clinical and angiographic features of iatrogenic occlusion of the ophthalmic artery and its branches caused by cosmetic facial filler injections. Data from 44 patients with occlusion of the ophthalmic artery and its branches after cosmetic facial filler injections were obtained retrospectively from a national survey completed by members of the Korean Retina Society from 27 retinal centers. Clinical features were compared between patients grouped by angiographic findings and injected filler material. Visual prognosis and its relationship to angiographic findings and injected filler material. Ophthalmic artery occlusion was classified into 6 types according to angiographic findings. Twenty-eight patients had diffuse retinal and choroidal artery occlusions (ophthalmic artery occlusion, generalized posterior ciliary artery occlusion, and central retinal artery occlusion). Sixteen patients had localized occlusions (localized posterior ciliary artery occlusion, branch retinal artery occlusion, and posterior ischemic optic neuropathy). Patients with diffuse occlusions showed worse initial and final visual acuity and less visual gain compared with those having localized occlusions. Patients receiving autologous fat injections (n = 22) had diffuse ophthalmic artery occlusions, worse visual prognosis, and a higher incidence of combined brain infarction compared with patients having hyaluronic acid injections (n = 13). Clinical features of iatrogenic occlusion of the ophthalmic artery and its branches following cosmetic facial filler injections were diverse according to the location and extent of obstruction and the injected filler material. Autologous fat injections were associated with a worse visual prognosis and a higher incidence of combined cerebral infarction. Extreme caution and care should be taken during these injections, and physicians should be aware of a diverse spectrum of complications following cosmetic facial filler injections.

Sci-Fri AM: Quality, Safety, and Professional Issues 06: An Evaluation of Incident Reporting and Learning using the Canadian National System for Incident Reporting – Radiation Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montgomery, Logan; Kildea, John

We report on the development and clinical deployment of an in-house incident reporting and learning system that implements the taxonomy of the Canadian National System for Incident Reporting – Radiation Treatment (NSIR-RT). In producing our new system, we aimed to: Analyze actual incidents, as well as potentially dangerous latent conditions. Produce recommendations on the NSIR-RT taxonomy. Incorporate features to divide reporting responsibility among clinical staff and expedite incident categorization within the NSIR-RT framework. Share anonymized incident data with the national database. Our multistep incident reporting workflow is focused around an initial report and a detailed follow-up investigation. An investigator, chosenmore » at the time of reporting, is tasked with performing the investigation. The investigation feature is connected to our electronic medical records database to allow automatic field population and quick reference of patient and treatment information. Additional features include a robust visualization suite, as well as the ability to flag incidents for discussion at monthly Risk Management meetings and task ameliorating actions to staff. Our system was deployed into clinical use in January 2016. Over the first three months of use, 45 valid incidents were reported; 31 of which were reported as actual incidents as opposed to near-misses or reportable circumstances. However, we suspect there is ambiguity within our centre in determining the appropriate event type, which may be arising from the taxonomy itself. Preliminary trending analysis aided in revealing workflow issues pertaining to storage of treatment accessories and treatment planning delays. Extensive analysis will be undertaken as more data are accrued.« less

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.

PubMed

Watanabe, Junko; Togo, Shinsaku; Sumiyoshi, Issei; Namba, Yukiko; Suina, Kentaro; Mizuno, Takafumi; Kadoya, Kotaro; Motomura, Hiroaki; Iwai, Moe; Nagaoka, Tetsutaro; Sasaki, Shinichi; Hayashi, Takuo; Uekusa, Toshimasa; Abe, Kanae; Urata, Yasuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Kato, Shunsuke; Takahashi, Kazuhisa

2018-05-08

Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement ( p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC ( p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome.

[Clinical features of a Chinese pedigree with Waardenburg syndrome type 2].

PubMed

Yang, Shu-zhi; Yuan, Hui-jun; Bai, Lin-na; Cao, Ju-yang; Xu, Ye; Shen, Wei-dong; Ji, Fei; Yang, Wei-yan

2005-10-12

To investigate detailed clinical features of a Chinese pedigree with Waardenburg syndrome type 2. Members of this pedigree were interviewed to identify personal or family medical histories of hearing loss, the use of aminoglycosides, and other clinical abnormalities by filling questionnaire. The audiological and other clinical evaluations of the proband and other members of this family were conducted, including pure-tone audiometry, immittance and auditory brain-stem response and ophthalmological, dermatologic, hair, temporal bone CT examinations. This family is categorized as Waardenburg syndrome type 2 according to its clinical features. It's an autosomal dominant disorder with incomplete penetrance. The clinical features varied greatly among family members and characterized by sensorineural hearing loss, heterochromia irides, freckle on the face and premature gray hair. Hearing loss can be unilateral or bilateral, congenital or late onset in this family. This Chinese family has some unique clinical features comparing with the international diagnostic criteria for Waardenburg syndrome. This study may provide some evidences to amend the diagnostic criteria for Waardenburg syndrome in Chinese population.

Nonresolving or slowly resolving pneumonia.

PubMed

Kuru, T; Lynch, J P

1999-09-01

Given the variability in rate of radiographic resolution, it remains controversial to decide when to initiate an invasive diagnostic work-up for nonresolving or slowly resolving pulmonary infiltrates. In immunocompetent patients who present with classical features of CAP (i.e., fever, chills, productive cough, new pulmonary infiltrate), clinical response to therapy is the most important determinant for further diagnostic studies. Within the first few days, persistence or even progression of infiltrates on chest radiographs is not unusual. Defervescence, diminished symptoms, and resolution of leukocytosis strongly support a response to antibiotic therapy, even when chest radiographic abnormalities persist. In this context, observation alone is reasonable, and invasive procedures can be deferred. Serial radiographs and clinical examinations dictate subsequent evaluation. In contrast, when clinical improvement has not occurred and chest radiographs are unchanged or worse, a more aggressive approach is warranted. In this setting, we advise fiberoptic bronchoscopy with BAL and appropriate cultures for bacteria, legionella, fungi, and mycobacteria. When endobronchial anatomy is normal and there is no purulence to suggest infection, TBBs should be done to exclude noninfectious causes (discussed earlier) or infections attributable to mycobacteria or fungi. An aggressive approach is also warranted in patients who are clinically stable or improving when the rate of radiographic resolution is delayed. As discussed earlier, what constitutes excessive delay is controversial, and depends upon the acuity of illness, specific pathogen, extent of involvement (i.e., lobar versus multilobar), comorbidities, and diverse host factors. Stable infiltrates even 2 to 4 weeks after institution of antibiotic therapy does not mandate intervention provided patients are improving clinically. Invasive techniques can also be deferred when unequivocal, albeit incomplete, radiographic resolution can be demonstrated. Lack of at least partial radiographic resolution by 6 weeks, even in asymptomatic patients, however, deserves consideration of alternative causes (e.g., endobronchial obstructing lesions, or noninfectious causes). Fiberoptic bronchoscopy with BAL and TBBs has minimal morbidity and is the preferred initial invasive procedure for detecting endobronchial lesions or substantiating noninfectious causes. The yield of bronchoscopy depends on demographics, radiographic features, and pre-test likelihood. In the absence of specific risk factors, the incidence of obstructing lesions (e.g., bronchogenic carcinomas, bronchial adenomas, obstructive foreign body) is low. Bronchogenic carcinoma is rare in nonsmoking, young (< 50 years) patients but is a legitimate consideration in older patients with a history of tobacco abuse. Non-neoplastic causes (e.g., pulmonary vasculitis, hypersensitivity pneumonia, etc.) should be considered when specific features are present (e.g., hematuria, appropriate epidemiologic exposures). Ancillary serologic tests or biopsies of extrapulmonary sites are invaluable in some cases. In rare instances, surgical (open or VATS) biopsy is necessary to diagnose refractory or non-resolving "pneumonias."

Gadolinium deposition disease: Initial description of a disease that has been around for a while.

PubMed

Semelka, Richard C; Ramalho, Joana; Vakharia, Ami; AlObaidy, Mamdoh; Burke, Lauren M; Jay, Michael; Ramalho, Miguel

2016-12-01

To describe the clinical manifestations of presumed gadolinium toxicity in patients with normal renal function. Participants were recruited from two online gadolinium toxicity support groups. The survey was anonymous and individuals were instructed to respond to the survey only if they had evidence of normal renal function, evidence of gadolinium in their system beyond 30days of this MRI, and no pre-existent clinical symptoms and/or signs of this type. 42 subjects responded to the survey (age: 28-69, mean 49.1±22.4years). The most common findings were: central pain (n=15), peripheral pain (n=26), headache (n=28), and bone pain (n=26). Only subjects with distal leg and arm distribution described skin thickening (n=22). Clouded mentation and headache were the symptoms described as persistent beyond 3months in 29 subjects. Residual disease was present in all patients. Twenty-eight patients described symptoms following administration of one brand of Gadolinium-Based Contrast Agent (GBCA), 21 after a single GBCA administration and 7 after multiple GBCA administrations, including: gadopentetate dimeglumine, n=9; gadodiamide, n=4; gadoversetamide, n=4; gadobenate dimeglumine, n=4; gadobutrol, n=1; gadoteridol, n=2; and unknown, n=4. Gadolinium toxicity appears to arise following GBCA administration, which appears to contain clinical features seen in Nephrogenic Systemic Fibrosis, but also features not observed in that condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Seizures versus dystonia in encephalopathic crisis of glutaric aciduria type I.

PubMed

Cerisola, Alfredo; Campistol, Jaume; Pérez-Dueñas, Belén; Poo, Pilar; Pineda, Mercé; García-Cazorla, Angels; Sanmartí, Francesc X; Ribes, Antonia; Vilaseca, María Antonia

2009-06-01

In more than two thirds of cases, glutaric aciduria type I begins in the first 3 years of life with an acute encephalopathic crisis with hypotonia or generalized rigidity, neurologic depression, irritability, seizures, and dystonia. The clinical histories were reviewed for 13 glutaric aciduria type I patients (9 male, 4 female; mean age, 8.7 months; range, 3-15 months) with encephalopathic crisis seen at Sant Joan de Déu Hospital, to describe the clinical features and the initial electroencephalographic (EEG) findings. Twelve of the patients (92%) had paroxysmal episodes at onset. Other clinical features included irritability (12/13), neurologic depression (11/13), and hypotonia (7/13). All patients evolved to dystonic tetraparesis. Thirty-five EEGs were recorded in the acute stage and during the first year of follow-up. Spike discharges on EEG were observed in only 2 of the 13 patients, and 8 had slow background activity. No patient developed seizures during follow-up. Seizures may be part of the symptomatology at the onset of glutaric aciduria type I, but most paroxysmal movements appear to be dystonic episodes. This hypothesis is supported by four facts: seizures do not occur after dystonic tetraparesis is noticed, EEG paroxysms are infrequent in the acute stage, antiepileptic drugs are not needed in the long term, and epilepsy is rare in the follow-up.

Clinical features and treatment of peristomal pyoderma gangrenosum.

PubMed

Hughes, A P; Jackson, J M; Callen, J P

2000-09-27

Peristomal pyoderma gangrenosum (PPG), an unusual variant of pyoderma gangrenosum, has been reported almost exclusively in patients with inflammatory bowel disease (IBD) and is frequently misdiagnosed. To better characterize the clinical manifestations, diagnosis, and management of PPG. Retrospective analysis of 7 patients with PPG observed in a university-affiliated community setting between 1988 and December 1999. Clinical and histopathologic features, associated disorders, and microbiologic findings. Two patients had Crohn disease, 2 had ulcerative colitis, and 3 had abdominal cancer. Five patients had at least 1 relapse of PPG after initial healing. Although 3 of 4 patients with IBD had active bowel disease, a parallel course with PPG occurred in only 1 patient. Both patients whose stoma was relocated developed an ulcer at the new site. Effective therapies included topical superpotent corticosteroids; intralesional injection of triamcinolone acetonide at the ulcer margin; topical cromolyn sodium; oral dapsone, prednisone, cyclosporine, mycophenolate mofetil; and intravenous infliximab. Our experiences demonstrate that although PPG has been most often reported in patients with IBD, it may occur in the absence of IBD. Biopsy of the skin lesion is not diagnostic but excludes other causes. Relocation of the stoma may be associated with a new ulceration and should be avoided. Trauma to the skin of a predisposed patient may elicit the pustules or ulcerations associated with pathergy. JAMA. 2000;284:1546-1548.

The development of a core syllabus for the teaching of head and neck anatomy to medical students.

PubMed

Tubbs, R Shane; Sorenson, Edward P; Sharma, Amit; Benninger, Brion; Norton, Neil; Loukas, Marios; Moxham, Bernard J

2014-04-01

The study of human anatomy has traditionally served as a fundamental component in the basic science education of medical students, yet there exists a remarkable lack of firm guidance on essential features that must be included in a gross anatomy course, which would constitute a "Core Syllabus" of absolutely mandatory structures and related clinical pathologies. While universal agreement on the details of a core syllabus is elusive, there is a general consensus that a core syllabus aims to identify the minimum level of knowledge expected of recently qualified medical graduates in order to carry out clinical procedures safely and effectively, while avoiding overloading students with unnecessary facts that have less immediate application to their future careers as clinicians. This paper aims to identify consensus standards of essential features of Head and Neck anatomy via a Delphi Panel consisting of anatomists and clinicians who evaluated syllabus content structures (greater than 1,000) as "essential", "important", "acceptable", or "not required." The goal is to provide guidance for program/course directors who intend to provide the optimal balance between establishing a comprehensive list of clinically relevant essential structures and an overwhelming litany, which would otherwise overburden trainees in their initial years of medical school with superficial rote learning, which potentially dilutes the key and enduring fundamental lessons that prepare students for training in any medical field. Copyright © 2014 Wiley Periodicals, Inc.

Myasthenia Gravis: Unusual Presentations and Diagnostic Pitfalls.

PubMed

Rodolico, Carmelo; Parisi, Daniela; Portaro, Simona; Biasini, Fiammetta; Sinicropi, Stefano; Ciranni, Annamaria; Toscano, Antonio; Messina, Sonia; Musumeci, Olimpia; Vita, Giuseppe; Girlanda, Paolo

2016-08-30

Myasthenia gravis (MG) is an autoimmune disorder presenting with fluctuating, fatigable muscle weakness. Initial symptoms classically involve ocular and proximal limb muscles. Rarely, MG may onset with unusual features, so it can be misdiagnosed with other neuromuscular diseases. To describe unusual and atypical presentations of MG in a large cohort of patients, considering and discussing diagnostic difficulties and pitfalls. We report on 21 out of 508 MG patients, coming to our department in the last 27 years and presenting with atypical or unusual features. The diagnosis was achieved performing a careful clinical examination, a proper neurophysiological assessment, the neostigmine test, the AChR and MuSK antibodies assay and chest CT-scan. Patients with atypical/unusual MG onset were the 4.4% of all MG patients population. We describe seven different clinical categories: asymmetric distal upper limbs weakness, foot drop, isolated triceps brachii weakness and foot drop, post exertional axial weakness with dropped head, acute facial dyplegia, limb-girdle MG and MG with sudden lower limbs weakness and recurrent falls. Atypical and unusual presentations may increase the risk to misdiagnose or delay MG diagnosis. Isolated limb-girdle presentation is the most frequent atypical form in our series.

Patient Characteristics by Type of Hypersexuality Referral: A Quantitative Chart Review of 115 Consecutive Male Cases.

PubMed

Sutton, Katherine S; Stratton, Natalie; Pytyck, Jennifer; Kolla, Nathan J; Cantor, James M

2015-01-01

Hypersexuality remains an increasingly common but poorly understood patient complaint. Despite diversity in clinical presentations of patients referred for hypersexuality, the literature has maintained treatment approaches that are assumed to apply to the entire phenomenon. This approach has proven ineffective, despite its application over several decades. The present study used quantitative methods to examine demographic, mental health, and sexological correlates of common clinical subtypes of hypersexuality referrals. Findings support the existence of subtypes, each with distinct clusters of features. Paraphilic hypersexuals reported greater numbers of sexual partners, more substance abuse, initiation to sexual activity at an earlier age, and novelty as a driving force behind their sexual behavior. Avoidant masturbators reported greater levels of anxiety, delayed ejaculation, and use of sex as an avoidance strategy. Chronic adulterers reported premature ejaculation and later onset of puberty. Designated patients were less likely to report substance abuse, employment, or finance problems. Although quantitative, this article nonetheless presents a descriptive study in which the underlying typology emerged from features most salient in routine sexological assessment. Future studies might apply purely empirical statistical techniques, such as cluster analyses, to ascertain to what extent similar typologies emerge when examined prospectively.

[Early diagnosis, variety of outcomes and prognosis of juvenile schizophrenia with over-value disorders of the "metaphysical intoxication" type onset (results of a late follow-up study)].

PubMed

Tsutsul'kovskaia, M Ia; Izvol'skiĭ, S A; Bol'zho, A G; Kopeĭko, G I

1986-01-01

On the basis of follow-up findings about juvenile schizophrenia first expressed in superworship manifestations according to the type of metaphysical intoxication (98 observations), the authors established that most frequently these cases were characterized by a torpid course of the disease in the framework of slowly progressing juvenile schizophrenia. There was a high rate of favourable outcomes at the level of "clinical recovery" (in 42.5%). Favourable prognostic signs were as follows: the complete nature of the clinical picture of the syndrome, its similarity to pubertal crisis manifestations, the absence in its structure of other positive disturbances and a number of specific features of the premorbid picture. The authors determined the pattern of correlation between the typological characteristics of the state of juvenile metaphysical intoxication and the outcome of the disease, peculiarities of manifestations of this phenomenon at the initial stage of psychotic forms of juvenile schizophrenia, as well as distinctive features of superworship formations according to the type of juvenile metaphysical intoxication observed in the framework of pubertal decompensation in schizoid psychopathies.

A Rare Combination of Functional Disomy Xp, Deletion Xq13.2-q28 Spanning the XIST Gene, and Duplication 3q25.33-q29 in a Female with der(X)t(X;3)(q13.2;q25.33).

PubMed

Peterson, Jess F; Basel, Donald G; Bick, David P; Chirempes, Brett; Lorier, Rachel B; Zemlicka, Nykula; Grignon, John W; Weik, LuAnn; Kappes, Ulrike

2018-03-01

We report a 19-year-old female patient with a history of short stature, primary ovarian insufficiency, sensorineural hearing loss, sacral teratoma, neurogenic bladder, and intellectual disability with underlying mosaicism for der(X)t(X;3)(q13.2;q25.33), a ring X chromosome, and monosomy X. Derivative X chromosomes from unbalanced X-autosomal translocations are preferentially silenced by the XIST gene (Xq13.2) located within the X-inactivation center. The unbalanced X-autosomal translocation in our case resulted in loss of the XIST gene thus precluding the inactivation of the derivative X chromosome. As a result, clinical features of functional disomy Xp, Turner's syndrome, and duplication 3q syndrome were observed. Importantly, indications of the derivative X chromosome were revealed by microarray analysis following an initial diagnosis of Turner's syndrome made by conventional cytogenetic studies approximately 18 months earlier. This case demonstrates the importance of utilizing microarray analysis as a first-line test in patients with clinical features beyond the scope of a well-defined genetic syndrome.

Central lactic acidosis, hyperventilation, and respiratory alkalosis: leading clinical features in a 3-year-old boy with malignant meningeal melanoma.

PubMed

Blüher, Susann; Schulz, Manuela; Bierbach, Uta; Meixensberger, Jürgen; Tröbs, Ralf-Bodo; Hirsch, Wolfgang; Schober, Ralf; Kiess, Wieland; Siekmeyer, Werner

2008-04-01

Meningeal tumors are extremely rare in children and are diagnostically as well as therapeutically challenging. Among the least common types of malignancies in childhood is malignant melanoma, counting for less than 1% of pediatric tumors. Due to the rarity and the wide spectrum of appearance, initial clinical features may be misleading. A 3-year-old boy was referred to our hospital with symptoms of hyperventilation, dyspnoea, tachycardia, respiratory alkalosis, inarticulate speech, and fatigue. Measurement of pH in cerebrospinal fluid (CSF) yielded central lactic acidosis despite alkalosis in peripheral blood. Diagnostic imaging procedures as well as histology and immunohistochemistry revealed the diagnosis of a malignant meningeal melanoma. We hypothesize that central lactate production of the tumor nests might have induced central acidification, thus inducing hyperventilation by stimulation of central chemoreceptors. This case is a model example of the key role of central pH as an inducer/suppressor of ventilation in humans and illustrates the critical importance of central pH for regulating both ventilation and acid-base homeostasis. Thus, pH of CSF should be measured whenever a malignant brain tumor is suspected.

Lobectomy is a more Cost-Effective Option than Total Thyroidectomy for 1 to 4 cm Papillary Thyroid Carcinoma that do not Possess Clinically Recognizable High-Risk Features.

PubMed

Lang, Brian Hung-Hin; Wong, Carlos K H

2016-10-01

Although lobectomy is a viable alternative to total thyroidectomy (TT) in low-risk 1 to 4 cm papillary thyroid carcinoma (PTC), lobectomy is associated with higher locoregional recurrence risk and need for completion TT upon discovery of a previously unrecognized histologic high-risk feature (HRF). The present study evaluated long-term cost-effectiveness between lobectomy and TT. Our base case was a hypothetical female cohort aged 40 years with a low-risk 2.5 cm PTC. A Markov decision tree model was constructed to compare cost-effectiveness between lobectomy and TT after 25 years. Patients with an unrecognized HRF (including aggressive histology, microscopic extrathyroidal extension, lymphovascular invasion, positive resection margin, nodal metastasis >5 mm, and multifocality) underwent completion TT after lobectomy. Outcome probabilities, utilities, and costs were estimated from the literature. The threshold for cost-effectiveness was set at US$50,000/quality-adjusted life-year (QALY). Sensitivity and threshold analyses were used to examine model uncertainty. After 25 years, each patient who underwent lobectomy instead of TT cost an extra US$772.08 but gained an additional 0.300 QALY. The incremental cost-effectiveness ratio was US$2577.65/QALY. In the sensitivity analysis, the lobectomy arm began to become cost-effective only after 3 years. Despite varying the reported prevalence of clinically unrecognized HRFs, complication from surgical procedures, annualized recurrence rates, unit cost of surgical procedure or complication, and utility score, lobectomy remained more cost-effective than TT. Despite the higher locoregional recurrence risk and having almost half of the patients undergoing completion TT after lobectomy upon discovery of a previously unrecognized HRF, initial lobectomy was a more cost-effective long-term option than initial TT for 1 to 4 cm PTCs without clinically recognized HRFs.

Using classification models for the generation of disease-specific medications from biomedical literature and clinical data repository.

PubMed

Wang, Liqin; Haug, Peter J; Del Fiol, Guilherme

2017-05-01

Mining disease-specific associations from existing knowledge resources can be useful for building disease-specific ontologies and supporting knowledge-based applications. Many association mining techniques have been exploited. However, the challenge remains when those extracted associations contained much noise. It is unreliable to determine the relevance of the association by simply setting up arbitrary cut-off points on multiple scores of relevance; and it would be expensive to ask human experts to manually review a large number of associations. We propose that machine-learning-based classification can be used to separate the signal from the noise, and to provide a feasible approach to create and maintain disease-specific vocabularies. We initially focused on disease-medication associations for the purpose of simplicity. For a disease of interest, we extracted potentially treatment-related drug concepts from biomedical literature citations and from a local clinical data repository. Each concept was associated with multiple measures of relevance (i.e., features) such as frequency of occurrence. For the machine purpose of learning, we formed nine datasets for three diseases with each disease having two single-source datasets and one from the combination of previous two datasets. All the datasets were labeled using existing reference standards. Thereafter, we conducted two experiments: (1) to test if adding features from the clinical data repository would improve the performance of classification achieved using features from the biomedical literature only, and (2) to determine if classifier(s) trained with known medication-disease data sets would be generalizable to new disease(s). Simple logistic regression and LogitBoost were two classifiers identified as the preferred models separately for the biomedical-literature datasets and combined datasets. The performance of the classification using combined features provided significant improvement beyond that using biomedical-literature features alone (p-value<0.001). The performance of the classifier built from known diseases to predict associated concepts for new diseases showed no significant difference from the performance of the classifier built and tested using the new disease's dataset. It is feasible to use classification approaches to automatically predict the relevance of a concept to a disease of interest. It is useful to combine features from disparate sources for the task of classification. Classifiers built from known diseases were generalizable to new diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical trial designs incorporating predictive biomarkers☆

PubMed Central

Renfro, Lindsay A.; Mallick, Himel; An, Ming-Wen; Sargent, Daniel J.; Mandrekar, Sumithra J.

2016-01-01

Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer “targeted” drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research. PMID:26827695

Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation.

PubMed

Lindquist, S G; Holm, I E; Schwartz, M; Law, I; Stokholm, J; Batbayli, M; Waldemar, G; Nielsen, J E

2008-04-01

We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic and affected family members underwent multidisciplinary (clinical, molecular, neuroimaging and neuropathological) examinations. Treatment with memantine in a family member with early symptoms, based on the clinical phenotype and the lack of specific treatment, appears to stabilize the disease course and increase the glucose metabolism in cortical and subcortical areas, as determined by serial [F(18)]FDG-PET scanning before and after initiation of treatment. Neuropathological examination of a second affected and mutation-positive family member showed moderate atrophy of the temporal lobes including the hippocampi. Microscopy revealed abundant numbers of tau-positive neurofibrillary tangles in all cortical areas and in some brainstem nuclei corresponding to a diagnosis of frontotemporal lobe degeneration on the basis of a MAPT mutation. The clinical and genetic heterogeneity of autosomal dominant inherited dementia must be taken into account in the genetic counselling and genetic testing of families with autosomal dominantly inherited dementia in general.

Universal suprapubic approach for complete mesocolic excision and central vascular ligation using the da Vinci Xi® system: from cadaveric models to clinical cases.

PubMed

Yeo, Shen Ann; Noh, Gyoung Tae; Han, Jeong Hee; Cheong, Chinock; Stein, Hubert; Kerdok, Amy; Min, Byung Soh

2017-12-01

There has been little enthusiasm for performing robotic colectomy for colon cancer in recent years due to multiple factors, one being that the previous robotic systems such as the da Vinci Si ® (dVSi) were poorly designed for multi-quadrant surgery. The new da Vinci Xi ® (dVXi) system enables colectomy with central mesocolic excision to be performed easily in a single docking procedure. We developed a universal port placement strategy to allow right and left hemicolectomies to be performed via a suprapubic approach and a Pfannensteil extraction site. This proof of concept paper describes the development and subsequent clinical application of this setup. After extensive training on the dVXi system concepts in collaboration with clinical development engineers, we developed a port placement strategy which was tested and adapted after performing experimental surgery in three cadaveric models. Subsequently our port placement was used for two clinical cases of suprapubic right and left hemicolectomy. With some modifications of port placements after the initial cadaveric colectomies, we have developed a potentially universal suprapubic port placement strategy for robotic colectomy with complete mesocolic excision and central vascular ligation using the dVXi robotic system. This port placement strategy was applied successfully in our first two clinical cases. Based on our cadaveric laboratory as well as our initial clinical application, the suprapubic port placement strategy for the dVXi system with its improved features over the dVSi can feasibly perform right and left hemicolectomy with complete mesocolic excision and central vascular ligation. Further studies will be required to establish efficacy as well as safety profile of these procedures.

Characteristic clinical features of Aspergillus appendicitis: Case report and literature review.

PubMed

Gjeorgjievski, Mihajlo; Amin, Mitual B; Cappell, Mitchell S

2015-11-28

This work aims to facilitate diagnosing Aspergillus appendicitis, which can be missed clinically due to its rarity, by proposing a clinical pentad for Aspergillus appendicitis based on literature review and one new case. The currently reported case of pathologically-proven Aspergillus appendicitis was identified by computerized search of pathology database at William Beaumont Hospital, 1999-2014. Prior cases were identified by computerized literature search. Among 10980 pathology reports of pathologically-proven appendicitis, one case of Aspergillus appendicitis was identified (rate = 0.01%). A young boy with profound neutropenia, recent chemotherapy, and acute myelogenous leukemia presented with right lower quadrant pain, pyrexia, and generalized malaise. Abdominal computed tomography scan showed a thickened appendiceal wall and periappendiceal inflammation, suggesting appendicitis. Emergent laparotomy showed an inflamed, thickened appendix, which was resected. The patient did poorly postoperatively with low-grade-fevers while receiving antibacterial therapy, but rapidly improved after initiating amphotericin therapy. Microscopic examination of a silver stain of the appendectomy specimen revealed fungi with characteristic Aspergillus morphology, findings confirmed by immunohistochemistry. Primary Aspergillus appendicitis is exceptionally rare, with only 3 previously reported cases. All three cases presented with (1)-neutropenia, (2)-recent chemotherapy, (3)-acute leukemia, and (4)-suspected appendicitis; (5)-the two prior cases initially treated with antibacterial therapy, fared poorly before instituting anti-Aspergillus therapy. The current patient satisfied all these five criteria. Based on these four cases, a clinical pentad is proposed for Aspergillus appendicitis: clinically-suspected appendicitis, neutropenia, recent chemotherapy, acute leukemia, and poor clinical response if treated solely by antibacterial/anti-candidial therapy. Patients presenting with this proposed pentad may benefit from testing for Aspergillus infection by silver-stains/immunohistochemistry and considering empirical anti-Aspergillus therapy pending a tissue diagnosis.

EHR based Genetic Testing Knowledge Base (iGTKB) Development

PubMed Central

2015-01-01

Background The gap between a large growing number of genetic tests and a suboptimal clinical workflow of incorporating these tests into regular clinical practice poses barriers to effective reliance on advanced genetic technologies to improve quality of healthcare. A promising solution to fill this gap is to develop an intelligent genetic test recommendation system that not only can provide a comprehensive view of genetic tests as education resources, but also can recommend the most appropriate genetic tests to patients based on clinical evidence. In this study, we developed an EHR based Genetic Testing Knowledge Base for Individualized Medicine (iGTKB). Methods We extracted genetic testing information and patient medical records from EHR systems at Mayo Clinic. Clinical features have been semi-automatically annotated from the clinical notes by applying a Natural Language Processing (NLP) tool, MedTagger suite. To prioritize clinical features for each genetic test, we compared odds ratio across four population groups. Genetic tests, genetic disorders and clinical features with their odds ratios have been applied to establish iGTKB, which is to be integrated into the Genetic Testing Ontology (GTO). Results Overall, there are five genetic tests operated with sample size greater than 100 in 2013 at Mayo Clinic. A total of 1,450 patients who was tested by one of the five genetic tests have been selected. We assembled 243 clinical features from the Human Phenotype Ontology (HPO) for these five genetic tests. There are 60 clinical features with at least one mention in clinical notes of patients taking the test. Twenty-eight clinical features with high odds ratio (greater than 1) have been selected as dominant features and deposited into iGTKB with their associated information about genetic tests and genetic disorders. Conclusions In this study, we developed an EHR based genetic testing knowledge base, iGTKB. iGTKB will be integrated into the GTO by providing relevant clinical evidence, and ultimately to support development of genetic testing recommendation system, iGenetics. PMID:26606281

EHR based Genetic Testing Knowledge Base (iGTKB) Development.

PubMed

Zhu, Qian; Liu, Hongfang; Chute, Christopher G; Ferber, Matthew

2015-01-01

The gap between a large growing number of genetic tests and a suboptimal clinical workflow of incorporating these tests into regular clinical practice poses barriers to effective reliance on advanced genetic technologies to improve quality of healthcare. A promising solution to fill this gap is to develop an intelligent genetic test recommendation system that not only can provide a comprehensive view of genetic tests as education resources, but also can recommend the most appropriate genetic tests to patients based on clinical evidence. In this study, we developed an EHR based Genetic Testing Knowledge Base for Individualized Medicine (iGTKB). We extracted genetic testing information and patient medical records from EHR systems at Mayo Clinic. Clinical features have been semi-automatically annotated from the clinical notes by applying a Natural Language Processing (NLP) tool, MedTagger suite. To prioritize clinical features for each genetic test, we compared odds ratio across four population groups. Genetic tests, genetic disorders and clinical features with their odds ratios have been applied to establish iGTKB, which is to be integrated into the Genetic Testing Ontology (GTO). Overall, there are five genetic tests operated with sample size greater than 100 in 2013 at Mayo Clinic. A total of 1,450 patients who was tested by one of the five genetic tests have been selected. We assembled 243 clinical features from the Human Phenotype Ontology (HPO) for these five genetic tests. There are 60 clinical features with at least one mention in clinical notes of patients taking the test. Twenty-eight clinical features with high odds ratio (greater than 1) have been selected as dominant features and deposited into iGTKB with their associated information about genetic tests and genetic disorders. In this study, we developed an EHR based genetic testing knowledge base, iGTKB. iGTKB will be integrated into the GTO by providing relevant clinical evidence, and ultimately to support development of genetic testing recommendation system, iGenetics.

Granulocytic sarcoma of the ovary in a nonleukemic patient.

PubMed

Aguiar, R C; Pozzi, D H; Chamone, D A

1993-01-01

We report a case of granulocytic sarcoma of the ovary preceding acute myeloid leukemia by twelve months, with no evidence of any hematological involvement at the time of first diagnosis. The patient was initially treated with surgery and chemotherapy for undifferentiated lymphoma and, although this aggressive protocol resulted in a complete response, granulocytic sarcoma recurred as extramedullary disease, followed by the appearance of acute myeloid leukemia. We discuss the clinical, histopathological and immunohistochemical features of the disease, the differential diagnosis and, in particular, the role of early aggressive treatment on the outcome of the patient.

Revision Surgical Treatment of a Second Lumbar Ewing Sarcoma: A Report of a Rare Case.

PubMed

Feng, Helin; Wang, Jin; Guo, Peng; Xu, Jianfa; Feng, Jiangang

2015-07-01

We report a case of a 58-year-old man who presented initially with lumbar pain.According to radiography, computed tomography, magnetic resonance imaging, and bone biopsy results, Ewing sarcoma (ES) was diagnosed. Tumor resection was performed, followed by chemotherapy and radiotherapy; pathology confirmed the diagnosis of ES. After surgery, the tumor recurred twice with progressive symptoms, meriting repeated excisional surgery. At the 4-year follow-up, the patient showed apparent improvement, with return of function and strength and resolution of pain.We discuss its clinical features and treatment in the light of the current knowledge.

Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network

PubMed Central

Morris, John C.; Aisen, Paul S.; Bateman, Randall J.; Benzinger, Tammie L.S.; Cairns, Nigel J.; Fagan, Anne M.; Ghetti, Bernardino; Goate, Alison M.; Holtzman, David M.; Klunk, William E.; McDade, Eric; Marcus, Daniel S.; Martins, Ralph N.; Masters, Colin L.; Mayeux, Richard; Oliver, Angela; Quaid, Kimberly; Ringman, John M.; Rossor, Martin N.; Salloway, Stephen; Schofield, Peter R.; Selsor, Natalie J.; Sperling, Reisa A.; Weiner, Michael W.; Xiong, Chengjie; Moulder, Krista L.; Buckles, Virginia D.

2012-01-01

The Dominantly Inherited Alzheimer Network (DIAN) is a collaborative effort of international Alzheimer disease (AD) centers that are conducting a multifaceted prospective biomarker study in individuals at-risk for autosomal dominant AD (ADAD). DIAN collects comprehensive information and tissue in accordance with standard protocols from asymptomatic and symptomatic ADAD mutation carriers and their non-carrier family members to determine the pathochronology of clinical, cognitive, neuroimaging, and fluid biomarkers of AD. This article describes the structure, implementation, and underlying principles of DIAN, as well as the demographic features of the initial DIAN cohort. PMID:23139856

Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network.

PubMed

Morris, John C; Aisen, Paul S; Bateman, Randall J; Benzinger, Tammie L S; Cairns, Nigel J; Fagan, Anne M; Ghetti, Bernardino; Goate, Alison M; Holtzman, David M; Klunk, William E; McDade, Eric; Marcus, Daniel S; Martins, Ralph N; Masters, Colin L; Mayeux, Richard; Oliver, Angela; Quaid, Kimberly; Ringman, John M; Rossor, Martin N; Salloway, Stephen; Schofield, Peter R; Selsor, Natalie J; Sperling, Reisa A; Weiner, Michael W; Xiong, Chengjie; Moulder, Krista L; Buckles, Virginia D

2012-10-01

The Dominantly Inherited Alzheimer Network (DIAN) is a collaborative effort of international Alzheimer disease (AD) centers that are conducting a multifaceted prospective biomarker study in individuals at-risk for autosomal dominant AD (ADAD). DIAN collects comprehensive information and tissue in accordance with standard protocols from asymptomatic and symptomatic ADAD mutation carriers and their non-carrier family members to determine the pathochronology of clinical, cognitive, neuroimaging, and fluid biomarkers of AD. This article describes the structure, implementation, and underlying principles of DIAN, as well as the demographic features of the initial DIAN cohort.

Fat Embolism Syndrome: A Case Report and Review Literature.

PubMed

Uransilp, Nattaphol; Muengtaweepongsa, Sombat; Chanalithichai, Nuttawut; Tammachote, Nattapol

2018-01-01

Fat embolism syndrome (FES) is a life-threatening complication in patients with orthopedic trauma, especially long bone fractures. The diagnosis of fat embolism is made by clinical features alone with no specific laboratory findings. FES has no specific treatment and requires supportive care, although it can be prevented by early fixation of bone fractures. Here, we report a case of FES in a patient with right femoral neck fracture, which was diagnosed initially by Gurd's criteria and subsequently confirmed by typical appearances on magnetic resonance imaging (MRI) of the brain. The patient received supportive management and a short course of intravenous methylprednisolone.

Acanthamoeba polyphaga mimivirus and other giant viruses: an open field to outstanding discoveries

PubMed Central

2014-01-01

In 2003, Acanthamoeba polyphaga mimivirus (APMV) was first described and began to impact researchers around the world, due to its structural and genetic complexity. This virus founded the family Mimiviridae. In recent years, several new giant viruses have been isolated from different environments and specimens. Giant virus research is in its initial phase and information that may arise in the coming years may change current conceptions of life, diversity and evolution. Thus, this review aims to condense the studies conducted so far about the features and peculiarities of APMV, from its discovery to its clinical relevance. PMID:24976356

Nodular Fasciitis in the Axillary Tail of the Breast

PubMed Central

Samardzic, Dejan; Chetlen, Alison; Malysz, Jozef

2014-01-01

Nodular fasciitis is a benign proliferation of myofibroblasts which presents clinically as a rapidly growing mass with nonspecific features on imaging and high cellular activity on histopathology. Nodular fasciitis can be mistaken for malignant fibrous lesions such as soft tissue sarcoma or breast carcinoma when located within breast tissue. This presents a problem for appropriate treatment planning as the natural history of nodular fasciitis is spontaneous regression. We present the mammographic, sonographic, computed tomography, and histopathologic characteristics of nodular fasciitis in a 68 year female initially presenting with a rapidly enlarging right axillary mass. PMID:25426226

Defining borderline patients: an overview.

PubMed

Gunderson, J G; Singer, M T

1975-01-01

This review of the descriptive literature on borderline patients indicates that accounts of such patients vary depending upon who is describing them, in what context, how the samples are selected, and what data are collected. The authors identify six features that provide a rational means for diagnosing borderline patients during an initial interview: the presence of intense affect, usually depressive or hostile; a history of impulsive behavior; a certain social adaptiveness; brief psychotic experiences; loose thinking in unstructured situations; and relationships that vacillate between transient superficiality and intense dependency. Reliable identification of these patients will permit better treatment planning and clinical research.

Successful medical treatment of an orbital osteoma in a dog.

PubMed

Grozdanic, Sinisa; Riedesel, Elizabeth A; Ackermann, Mark R

2013-03-01

A 6-year-old neutered male German Shepherd-mixed breed with a 2-month history of bilateral conjunctival hyperemia, epiphora, and a firm, slowly progressive swelling of the medial canthal region of the left eye (OS) was examined. Ophthalmic examination OS revealed a firm and smooth mass, extending from the medial canthus toward the medial orbital wall. Indirect ophthalmoscopy revealed indentation of the nasal part OS, which corresponded to the position of the orbital mass. Orbital neoplastic diseases were the main differential considerations. Computerized tomography revealed a bony smooth orbital mass without bone destructive features. Biopsy was performed, and histologic features were suggestive of osteoma. Systemic nonsteroidal anti-inflammatory (NSAID) drugs resulted in complete mass regression and absence of clinical signs for 5 years following initial diagnosis. This report describes the first case of canine orbital osteoma, which was responsive to NSAIDs. © 2012 American College of Veterinary Ophthalmologists.

Intracranial hypotension and hypertension in children and adolescents.

PubMed

Ozge, Aynur; Bolay, Hayrunnisa

2014-07-01

The specific aim of this review is to report the features of intracranial pressure changes [spontaneous intracranial hypotension (SIH) and idiopathic intracranial hypertension (IIH)] in children and adolescents, with emphasis on the presentation, diagnosis, and treatment modalities. Headache associated with intracranial pressure changes are relatively rare and less known in children and adolescents. SIH is a specific syndrome involving reduced intracranial pressure with orthostatic headache, frequently encountered connective tissue disorders, and a good prognosis with medical management, initial epidural blood patching, and sometimes further interventions may be required. IIH is an uncommon condition in children and different from the disease in adults, not only with respect to clinical features (likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus) but also different in outcome. Consequently, specific ICP changes of pediatric ages required specific attention both of exact diagnosis and entire management.

Parasitic causes of prolonged diarrhoea in travellers - diagnosis and management.

PubMed

Slack, Andrew

2012-10-01

Prolonged infectious diarrhoea in the returning traveller is generally caused by protozoal and occasionally by helminth parasites. This article provides a framework for the diagnosis, management and prevention of the diseases that cause persistent diarrhoea in the traveller. A large proportion of disease is caused by Giardia lamblia, Cryptosporidium parvum and Entamoeba histolytica. However, given the ease of travel with comorbid conditions such as human immunodeficiency virus, there is an expanding list of organisms that can cause persistent diarrhoea. An awareness of the likely aetiological agents and their clinical features enables a more effective diagnosis and management of the patient's condition using an appropriate antiparasitic agent. Prevention strategies need to be initiated before travel and should consist of simple but memorable advice. Noninfectious causes of diarrhoea should be considered as diarrhoea can be a prominent feature of conditions such as hyperthyroidism or coeliac disease.

Nasopharyngeal Carcinoma with Cystic Cervical Metastasis Masquerading as Branchial Cleft Cyst: A Potential Pitfall in Diagnosis and Management.

PubMed

Sai-Guan, Lum; Min-Han, Kong; Kah-Wai, Ngan; Mohamad-Yunus, Mohd-Razif

2017-03-01

Most metastatic lymph nodes from head and neck malignancy are solid. Cystic nodes are found in 33% - 61% of carcinomas arise from Waldeyer's ring, of which only 1.8% - 8% originate are from the nasopharynx. Some cystic cervical metastases were initially presumed to be branchial cleft cyst. This case report aims to highlight the unusual presentation of cystic cervical metastasis secondary to nasopharyngeal carcinoma in a young adult. The histopathology, radiological features and management strategy were discussed. A 36-year-old man presented with a solitary cystic cervical swelling, initially diagnosed as branchial cleft cyst. Fine needle aspiration yielded 18 ml of straw-coloured fluid. During cytological examination no atypical cells were observed. Computed tomography of the neck showed a heterogeneous mass with multiseptation medial to the sternocleidomastoid muscle. Histopathological examination of the mass, post excision, revealed a metastatic lymph node. A suspicious mucosal lesion at the nasopharynx was detected after repeated thorough head and neck examinations and the biopsy result confirmed undifferentiated nasopharyngeal carcinoma. Cystic cervical metastasis may occur in young patients under 40 years. The primary tumour may not be obvious during initial presentation because it mimicks benign branchial cleft cyst clinically. Retrospective review of the computed tomography images revealed features that were not characteristic of simple branchial cleft cyst. The inadequacy of assessment and interpretation had lead to the error in diagnosis and subsequent management. Metastatic head and neck lesion must be considered in a young adult with a cystic neck mass.

Classification of clinically useful sentences in clinical evidence resources.

PubMed

Morid, Mohammad Amin; Fiszman, Marcelo; Raja, Kalpana; Jonnalagadda, Siddhartha R; Del Fiol, Guilherme

2016-04-01

Most patient care questions raised by clinicians can be answered by online clinical knowledge resources. However, important barriers still challenge the use of these resources at the point of care. To design and assess a method for extracting clinically useful sentences from synthesized online clinical resources that represent the most clinically useful information for directly answering clinicians' information needs. We developed a Kernel-based Bayesian Network classification model based on different domain-specific feature types extracted from sentences in a gold standard composed of 18 UpToDate documents. These features included UMLS concepts and their semantic groups, semantic predications extracted by SemRep, patient population identified by a pattern-based natural language processing (NLP) algorithm, and cue words extracted by a feature selection technique. Algorithm performance was measured in terms of precision, recall, and F-measure. The feature-rich approach yielded an F-measure of 74% versus 37% for a feature co-occurrence method (p<0.001). Excluding predication, population, semantic concept or text-based features reduced the F-measure to 62%, 66%, 58% and 69% respectively (p<0.01). The classifier applied to Medline sentences reached an F-measure of 73%, which is equivalent to the performance of the classifier on UpToDate sentences (p=0.62). The feature-rich approach significantly outperformed general baseline methods. This approach significantly outperformed classifiers based on a single type of feature. Different types of semantic features provided a unique contribution to overall classification performance. The classifier's model and features used for UpToDate generalized well to Medline abstracts. Copyright © 2016 Elsevier Inc. All rights reserved.

Automatic Image Registration of Multimodal Remotely Sensed Data with Global Shearlet Features

NASA Technical Reports Server (NTRS)

Murphy, James M.; Le Moigne, Jacqueline; Harding, David J.

2015-01-01

Automatic image registration is the process of aligning two or more images of approximately the same scene with minimal human assistance. Wavelet-based automatic registration methods are standard, but sometimes are not robust to the choice of initial conditions. That is, if the images to be registered are too far apart relative to the initial guess of the algorithm, the registration algorithm does not converge or has poor accuracy, and is thus not robust. These problems occur because wavelet techniques primarily identify isotropic textural features and are less effective at identifying linear and curvilinear edge features. We integrate the recently developed mathematical construction of shearlets, which is more effective at identifying sparse anisotropic edges, with an existing automatic wavelet-based registration algorithm. Our shearlet features algorithm produces more distinct features than wavelet features algorithms; the separation of edges from textures is even stronger than with wavelets. Our algorithm computes shearlet and wavelet features for the images to be registered, then performs least squares minimization on these features to compute a registration transformation. Our algorithm is two-staged and multiresolution in nature. First, a cascade of shearlet features is used to provide a robust, though approximate, registration. This is then refined by registering with a cascade of wavelet features. Experiments across a variety of image classes show an improved robustness to initial conditions, when compared to wavelet features alone.

Automatic Image Registration of Multi-Modal Remotely Sensed Data with Global Shearlet Features

PubMed Central

Murphy, James M.; Le Moigne, Jacqueline; Harding, David J.

2017-01-01

Automatic image registration is the process of aligning two or more images of approximately the same scene with minimal human assistance. Wavelet-based automatic registration methods are standard, but sometimes are not robust to the choice of initial conditions. That is, if the images to be registered are too far apart relative to the initial guess of the algorithm, the registration algorithm does not converge or has poor accuracy, and is thus not robust. These problems occur because wavelet techniques primarily identify isotropic textural features and are less effective at identifying linear and curvilinear edge features. We integrate the recently developed mathematical construction of shearlets, which is more effective at identifying sparse anisotropic edges, with an existing automatic wavelet-based registration algorithm. Our shearlet features algorithm produces more distinct features than wavelet features algorithms; the separation of edges from textures is even stronger than with wavelets. Our algorithm computes shearlet and wavelet features for the images to be registered, then performs least squares minimization on these features to compute a registration transformation. Our algorithm is two-staged and multiresolution in nature. First, a cascade of shearlet features is used to provide a robust, though approximate, registration. This is then refined by registering with a cascade of wavelet features. Experiments across a variety of image classes show an improved robustness to initial conditions, when compared to wavelet features alone. PMID:29123329

Using GIS for spatial analysis of rectal lesions in the human body.

PubMed

Garb, Jane L; Ganai, Sabha; Skinner, Ric; Boyd, Christopher S; Wait, Richard B

2007-03-15

Geographic Information Systems (GIS) have been used in a wide variety of applications to integrate data and explore the spatial relationship of geographic features. Traditionally this has referred to features on the surface of the earth. However, it is possible to apply GIS in medicine, at the scale of the human body, to visualize and analyze anatomic and clinical features. In the present study we used GIS to examine the findings of transanal endoscopic microsurgery (TEM), a minimally-invasive procedure to locate and remove both benign and cancerous lesions of the rectum. Our purpose was to determine whether anatomic features of the human rectum and clinical findings at the time of surgery could be rendered in a GIS and spatially analyzed for their relationship to clinical outcomes. Maps of rectal topology were developed in two and three dimensions. These maps highlight anatomic features of the rectum and the location of lesions found on TEM. Spatial analysis demonstrated a significant relationship between anatomic location of the lesion and procedural failure. This study demonstrates the feasibility of rendering anatomical locations and clinical events in a GIS and its value in clinical research. This allows the visualization and spatial analysis of clinical and pathologic features, increasing our awareness of the relationship between anatomic features and clinical outcomes as well as enhancing our understanding and management of this disease process.

Using GIS for spatial analysis of rectal lesions in the human body

PubMed Central

Garb, Jane L; Ganai, Sabha; Skinner, Ric; Boyd, Christopher S; Wait, Richard B

2007-01-01

Background Geographic Information Systems (GIS) have been used in a wide variety of applications to integrate data and explore the spatial relationship of geographic features. Traditionally this has referred to features on the surface of the earth. However, it is possible to apply GIS in medicine, at the scale of the human body, to visualize and analyze anatomic and clinical features. In the present study we used GIS to examine the findings of transanal endoscopic microsurgery (TEM), a minimally-invasive procedure to locate and remove both benign and cancerous lesions of the rectum. Our purpose was to determine whether anatomic features of the human rectum and clinical findings at the time of surgery could be rendered in a GIS and spatially analyzed for their relationship to clinical outcomes. Results Maps of rectal topology were developed in two and three dimensions. These maps highlight anatomic features of the rectum and the location of lesions found on TEM. Spatial analysis demonstrated a significant relationship between anatomic location of the lesion and procedural failure. Conclusion This study demonstrates the feasibility of rendering anatomical locations and clinical events in a GIS and its value in clinical research. This allows the visualization and spatial analysis of clinical and pathologic features, increasing our awareness of the relationship between anatomic features and clinical outcomes as well as enhancing our understanding and management of this disease process. PMID:17362510

Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases.

PubMed

Scriven, James E; Scobie, Antonia; Verlander, Neville Q; Houston, Angela; Collyns, Tim; Cajic, Vjeran; Kon, Onn Min; Mitchell, Tamara; Rahama, Omar; Robinson, Amy; Withama, Shirmila; Wilson, Peter; Maxwell, David; Agranoff, Daniel; Davies, Eleri; Llewelyn, Meirion; Soo, Shiu-Shing; Sahota, Amandip; Cooper, Mike; Hunter, Michael; Tomlins, Jennifer; Tiberi, Simon; Kendall, Simon; Dedicoat, Martin; Alexander, Eliza; Fenech, Teresa; Zambon, Maria; Lamagni, Theresa; Smith, E Grace; Chand, Meera

2018-05-24

Mycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater-cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases. Case note review was performed for cases identified retrospectively through outbreak investigations and prospectively through on-going surveillance. Case definition was Mycobacterium chimaera detected in any clinical specimen, history of cardiothoracic surgery with cardiopulmonary bypass, and compatible clinical presentation. Thirty patients were identified (28 with prosthetic material) exhibiting a spectrum of disease including prosthetic valve endocarditis (14/30), sternal wound infection (2/30), aortic graft infection (4/30), and disseminated (non-cardiac) disease (10/30). Patients presented a median of 14 months post surgery (maximum 5 years) most commonly complaining of fever and weight loss. Investigations frequently revealed lymphopenia, thrombocytopenia, liver cholestasis and non-necrotising granulomatous inflammation. Diagnostic sensitivity for a single mycobacterial blood culture was 68% but increased if multiple samples were sent. 27 patients started macrolide-based combination treatment and 14 had further surgery. To date, 18 patients have died (60%) a median of 30 months (IQR 20-39) after initial surgery. Survival analysis identified younger age, mitral valve surgery, mechanical valve replacement, higher serum sodium concentration and lower CRP as factors associated with better survival. Mycobacterium chimaera infection following cardiac surgery is associated with a wide spectrum of disease. The diagnosis should be considered in all patients who develop an unexplained illness following cardiac surgery. Copyright © 2018. Published by Elsevier Ltd.

Evidence-based decision-making as a practice-based learning skill: a pilot study.

PubMed

Falzer, Paul R; Garman, D Melissa

2012-03-01

As physicians are being trained to adapt their practices to the needs and experience of patients, initiatives to standardize care have been gaining momentum. The resulting conflict can be addressed through a practice-based learning and improvement (PBL) program that develops competency in using treatment guidelines as decision aids and incorporating patient-specific information into treatment recommendations. This article describes and tests a program that is consistent with the ACGME's multilevel competency-based approach, targets students at four levels of training, and features progressive learning objectives and assessments. The program was pilot-tested with 22 paid volunteer psychiatric residents and fellows. They were introduced to a schizophrenia treatment guideline and reviewed six case vignettes of varying complexity. PBL assessments were based on how treatment recommendations were influenced by clinical and patient-specific factors. The task permitted separate assessments of learning objectives all four training levels. Among the key findings at each level, most participants found the treatment guideline helpful in making treatment decisions. Recommendations were influenced by guideline-based assessment criteria and other clinical features. They were also influenced by patients' perceptions of their illness, patient-based progress assessments, and complications such as stressors and coping patterns. Recommendations were strongly influenced by incongruence between clinical facts and patient experience. Practical understanding of how patient experience joins with clinical knowledge can enhance the use of treatment guidelines as decision tools and enable clinicians to appreciate more fully how and why patients' perceptions of their illness should influence treatment recommendations. This PBL program can assist training facilities in preparing students to cope with contradictory demands to both standardize and adapt their practice. The program can be modified to accommodate various disorders and a range of clinical factors and patient-specific complications.

Molecular mechanisms involved in vascular interactions of the Lyme disease pathogen in a living host.

PubMed

Norman, M Ursula; Moriarty, Tara J; Dresser, Ashley R; Millen, Brandie; Kubes, Paul; Chaconas, George

2008-10-03

Hematogenous dissemination is important for infection by many bacterial pathogens, but is poorly understood because of the inability to directly observe this process in living hosts at the single cell level. All disseminating pathogens must tether to the host endothelium despite significant shear forces caused by blood flow. However, the molecules that mediate tethering interactions have not been identified for any bacterial pathogen except E. coli, which tethers to host cells via a specialized pillus structure that is not found in many pathogens. Furthermore, the mechanisms underlying tethering have never been examined in living hosts. We recently engineered a fluorescent strain of Borrelia burgdorferi, the Lyme disease pathogen, and visualized its dissemination from the microvasculature of living mice using intravital microscopy. We found that dissemination was a multistage process that included tethering, dragging, stationary adhesion and extravasation. In the study described here, we used quantitative real-time intravital microscopy to investigate the mechanistic features of the vascular interaction stage of B. burgdorferi dissemination. We found that tethering and dragging interactions were mechanistically distinct from stationary adhesion, and constituted the rate-limiting initiation step of microvascular interactions. Surprisingly, initiation was mediated by host Fn and GAGs, and the Fn- and GAG-interacting B. burgdorferi protein BBK32. Initiation was also strongly inhibited by the low molecular weight clinical heparin dalteparin. These findings indicate that the initiation of spirochete microvascular interactions is dependent on host ligands known to interact in vitro with numerous other bacterial pathogens. This conclusion raises the intriguing possibility that fibronectin and GAG interactions might be a general feature of hematogenous dissemination by other pathogens.

Actinic Prurigo Cheilitis: A Clinicopathologic Review of 75 Cases.

PubMed

Plaza, Jose A; Toussaint, Sonia; Prieto, Victor G; Mercadillo, Patricia; Diez de Medina, Juan C; Lourenco, Silvia; Batdorf, Bjorn; Sangueza, Martin

2016-06-01

Actinic prurigo (AP) is a chronic idiopathic photodermatosis that primarily affects American Indians in the United States and Mestizos in Latin American countries. Clinically, the onset of the disease is usually in the first decade of life but may appear initially in adult life, and it is characterized by symmetric involvement of sun-exposed areas of the skin, particularly areas of the face, resulting in polymorphic erythematous papules, macules, and plaques in different stages of evolution. Lower lip involvement includes swelling, scaling, fissures, hyperpigmentation, and ulcerations of the vermilion border. and in some cases could represent the only manifestation of the disease. The histopathologic features of AP have been studied; however, there is a controversy regarding whether AP cheilitis has distinct histopathologic features that could allow accurate separation from other specific and nonspecific forms of cheilitis. The diagnosis can be challenging, mainly when lip lesions are the only manifestation of the disease. In this study, the authors investigate the clinicopathologic features of 75 cases of AP cheilitis to provide further criteria for its diagnosis and classification. All 75 patients presented with lip lesions. Thirty-three cases were diagnosed as AP cheilitis with cutaneous lesions and 42 cases were diagnosed as AP cheilitis without cutaneous lesions (only lip lesions). Histologically, of the 33 cases with AP cheilitis with cutaneous lesions, 17 (52%) cases showed follicular cheilitis, and of the 42 cases that had only lip lesions, 18 (43%) cases showed follicular cheilitis. Histologically, AP cheilitis can present as follicular cheilitis; thus, supporting the diagnosis. Also, our findings confirm that lip lesions can present as the only manifestation of the disease, showing typical histological and clinical features. This form of cheilitis has not being well described in the dermatologic and dermatopathologic literature.

Benign and Malignant Proliferative Fibro-osseous and Osseous Lesions of the Oral Cavity of Dogs.

PubMed

Soltero-Rivera, M; Engiles, J B; Reiter, A M; Reetz, J; Lewis, J R; Sánchez, M D

2015-09-01

Ossifying fibroma (OF) and fibrous dysplasia (FD) are benign, intraosseous, proliferative fibro-osseous lesions (PFOLs) characterized by replacement of normal bone by a fibrous matrix with various degrees of mineralization and ossification. Osteomas are benign tumors composed of mature, well-differentiated bone. Clinical, imaging, and histologic features of 15 initially diagnosed benign PFOLs and osteomas of the canine oral cavity were evaluated. Final diagnoses after reevaluation were as follows: OF (3 cases), FD (4 cases), low-grade osteosarcoma (LG-OSA) (3 cases), and osteoma (5 cases). Histology alone often did not result in a definitive diagnosis for PFOL. OF appeared as a well-circumscribed, radiopaque mass with some degree of bone lysis on imaging. Most lesions of FD showed soft tissue opacity with bone lysis and ill-defined margins. Low-grade OSA appeared as a lytic lesion with a mixed opacity and ill-defined margins. Osteomas were characterized by a mineralized, expansile, well-circumscribed lesion. Although histologic features of PFOLs were typically bland, the lesions diagnosed as LG-OSA had some features of malignancy (eg, bone invasion or a higher mitotic index). Treatment varied widely. Of the 10 dogs with benign PFOL or osteoma with known outcome (10/12), 9 showed either complete response (6/10) or stable disease (3/10) after treatment. Of the 2 dogs with LG-OSA with known outcome, 1 showed complete response after curative intent surgery, but 1 patient had recurrence after partial maxillectomy. Definitive diagnosis of mandibular/maxillary PFOL is challenging via histopathologic examination alone, and accurate diagnosis is best achieved through assimilation of clinical, imaging, and histopathologic features. © The Author(s) 2015.

Genotypic and phenotypic predictors of inflammation in patients with chronic kidney disease.

PubMed

Luttropp, Karin; Debowska, Malgorzata; Lukaszuk, Tomasz; Bobrowski, Leon; Carrero, Juan Jesus; Qureshi, Abdul Rashid; Stenvinkel, Peter; Lindholm, Bengt; Waniewski, Jacek; Nordfors, Louise

2016-12-01

In complex diseases such as chronic kidney disease (CKD), the risk of clinical complications is determined by interactions between phenotypic and genotypic factors. However, clinical epidemiological studies rarely attempt to analyse the combined effect of large numbers of phenotype and genotype features. We have recently shown that the relaxed linear separability (RLS) model of feature selection can address such complex issues. Here, it is applied to identify risk factors for inflammation in CKD. The RLS model was applied in 225 CKD stage 5 patients sampled in conjunction with dialysis initiation. Fifty-seven anthropometric or biochemical measurements and 79 genetic polymorphisms were entered into the model. The model was asked to identify phenotypes and genotypes that, when combined, could separate inflamed from non-inflamed patients. Inflammation was defined as a high-sensitivity C-reactive protein concentration above the median (5 mg/L). Among the 60 genotypic and phenotypic features predicting inflammation, 31 were genetic. Among the 10 strongest predictors of inflammation, 8 were single nucleotide polymorphisms located in the NAMPT, CIITA, BMP2 and PIK3CB genes, whereas fibrinogen and bone mineral density were the only phenotypic biomarkers. These results indicate a larger involvement of hereditary factors in inflammation than might have been expected and suggest that inclusion of genotype features in risk assessment studies is critical. The RLS model demonstrates that inflammation in CKD is determined by an extensive panel of factors and may prove to be a suitable tool that could enable a much-needed multifactorial approach as opposed to the commonly utilized single-factor analysis. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report.

PubMed

Lei, Hongen; Guan, Xing; Han, Hu; Qian, Xiaosong; Zhou, Xiaoguang; Zhang, Xiaodong; Tian, Long

2018-06-01

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by a triad of cutaneous port wine capillary malformations, varicose veins, and hemihypertrophy of bone and soft tissues. To report on a rare case of KTS in an adult man manifested by painless urethral bleeding during penile erection briefly review the clinical presentation and management of the genitourinary forms of this syndrome. On presentation, the clinical features of this patient, including medical history, signs and symptoms, and imaging examinations, were recorded. After diagnosis and initial treatment, a literature review of the urethral features of KTS was performed and is discussed in this report. A 35-year-old man with KTS presented with painless urethral bleeding during penile erection that was associated with posterior urethral vascular malformations. The coagulation method was used to treat the malformation, and no urethral bleeding or gross hematuria occurred during a postoperative follow-up period of 6 months. This case demonstrates that coagulation therapy and careful follow-up can be adequate treatment approaches for urethral features of KTS. However, the long-term efficacy of coagulation for this disorder should be investigated further. Lei H, Guan X, Han H, et al. Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report. Sex Med 2018;6:180-183. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Multi-region analysis of longitudinal FDG-PET for the classification of Alzheimer’s disease

PubMed Central

Gray, Katherine R.; Wolz, Robin; Heckemann, Rolf A.; Aljabar, Paul; Hammers, Alexander; Rueckert, Daniel

2012-01-01

Imaging biomarkers for Alzheimer’s disease are desirable for improved diagnosis and monitoring, as well as drug discovery. Automated image-based classification of individual patients could provide valuable diagnostic support for clinicians, when considered alongside cognitive assessment scores. We investigate the value of combining cross-sectional and longitudinal multi-region FDG-PET information for classification, using clinical and imaging data from the Alzheimer’s Disease Neuroimaging Initiative. Whole-brain segmentations into 83 anatomically defined regions were automatically generated for baseline and 12-month FDG-PET images. Regional signal intensities were extracted at each timepoint, as well as changes in signal intensity over the follow-up period. Features were provided to a support vector machine classifier. By combining 12-month signal intensities and changes over 12 months, we achieve significantly increased classification performance compared with using any of the three feature sets independently. Based on this combined feature set, we report classification accuracies of 88% between patients with Alzheimer’s disease and elderly healthy controls, and 65% between patients with stable mild cognitive impairment and those who subsequently progressed to Alzheimer’s disease. We demonstrate that information extracted from serial FDG-PET through regional analysis can be used to achieve state-of-the-art classification of diagnostic groups in a realistic multi-centre setting. This finding may be usefully applied in the diagnosis of Alzheimer’s disease, predicting disease course in individuals with mild cognitive impairment, and in the selection of participants for clinical trials. PMID:22236449

[A report of atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum caused by a de novo mutation in tubulin beta 4A (TUBB4A) gene and literature review].

PubMed

Du, Y; Li, C; Guo, J; Guo, P; Li, Z Y; Zhang, W

2017-06-01

Objective: To explore the clinical symptoms and neuroimaging features of a patient with atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum (H-ABC) caused by a novel TUBB4A mutation. Methods: We analyzed the clinical data, imaging features and the result of genetic testing of a case diagnosed as atypical H-ABC. Results: The initial symptoms were progressive spasticity, mild cerebellar ataxia and mild cognitive impairment. MRI showed regional blurring of slight high signal on T(2)-weight and FLAIR image in white matter of the bilateral midbrain ventral, internal capsule, posteior horn of lateral ventricle and centrum semiovale, with normal bilateral cerebellar and caudoputamen nucleus. Compared with normal subjects of the same age and gender, hypometabolism was found by (18)F-FDG-PET in brainstem, cerebellar and caudoputamen nucleus in the patient. Genetic testing revealed a de novo pathogenic exome missense heterozygous mutations c. 70G>A in TUBB4A, which was not reported in the human gene mutation database (HGMDpro) and was assessed to be a pathogenic mutation by pathogenic mutation prediction software. Conclusions: The diversity of TUBB4A gene mutations may cause different functional and/or structural impairment in subcortical white matter, cerebellar and caudoputamen nucleus, leading to atypical symptoms and neuroimaging features. Genetic testing for pathogenic mutation in TUBB 4A gene is a key for the diagnosis of H - ABC .

Extraction of 3D Femur Neck Trabecular Bone Architecture from Clinical CT Images in Osteoporotic Evaluation: a Novel Framework.

PubMed

Sapthagirivasan, V; Anburajan, M; Janarthanam, S

2015-08-01

The early detection of osteoporosis risk enhances the lifespan and quality of life of an individual. A reasonable in-vivo assessment of trabecular bone strength at the proximal femur helps to evaluate the fracture risk and henceforth, to understand the associated structural dynamics on occurrence of osteoporosis. The main aim of our study was to develop a framework to automatically determine the trabecular bone strength from clinical femur CT images and thereby to estimate its correlation with BMD. All the 50 studied south Indian female subjects aged 30 to 80 years underwent CT and DXA measurements at right femur region. Initially, the original CT slices were intensified and active contour model was utilised for the extraction of the neck region. After processing through a novel process called trabecular enrichment approach (TEA), the three dimensional (3D) trabecular features were extracted. The extracted 3D trabecular features, such as volume fraction (VF), solidity of delta points (SDP) and boundness, demonstrated a significant correlation with femoral neck bone mineral density (r = 0.551, r = 0.432, r = 0.552 respectively) at p < 0.001. The higher area under the curve values of the extracted features (VF: 85.3 %; 95CI: 68.2-100 %, SDP: 82.1 %; 95CI: 65.1-98.9 % and boundness: 90.4 %; 95CI: 78.7-100 %) were observed. The findings suggest that the proposed framework with TEA method would be useful for spotting women vulnerable to osteoporotic risk.

Visual Aggregate Analysis of Eligibility Features of Clinical Trials

PubMed Central

He, Zhe; Carini, Simona; Sim, Ida; Weng, Chunhua

2015-01-01

Objective To develop a method for profiling the collective populations targeted for recruitment by multiple clinical studies addressing the same medical condition using one eligibility feature each time. Methods Using a previously published database COMPACT as the backend, we designed a scalable method for visual aggregate analysis of clinical trial eligibility features. This method consists of four modules for eligibility feature frequency analysis, query builder, distribution analysis, and visualization, respectively. This method is capable of analyzing (1) frequently used qualitative and quantitative features for recruiting subjects for a selected medical condition, (2) distribution of study enrollment on consecutive value points or value intervals of each quantitative feature, and (3) distribution of studies on the boundary values, permissible value ranges, and value range widths of each feature. All analysis results were visualized using Google Charts API. Five recruited potential users assessed the usefulness of this method for identifying common patterns in any selected eligibility feature for clinical trial participant selection. Results We implemented this method as a Web-based analytical system called VITTA (Visual Analysis Tool of Clinical Study Target Populations). We illustrated the functionality of VITTA using two sample queries involving quantitative features BMI and HbA1c for conditions “hypertension” and “Type 2 diabetes”, respectively. The recruited potential users rated the user-perceived usefulness of VITTA with an average score of 86.4/100. Conclusions We contributed a novel aggregate analysis method to enable the interrogation of common patterns in quantitative eligibility criteria and the collective target populations of multiple related clinical studies. A larger-scale study is warranted to formally assess the usefulness of VITTA among clinical investigators and sponsors in various therapeutic areas. PMID:25615940

Visual aggregate analysis of eligibility features of clinical trials.

PubMed

He, Zhe; Carini, Simona; Sim, Ida; Weng, Chunhua

2015-04-01

To develop a method for profiling the collective populations targeted for recruitment by multiple clinical studies addressing the same medical condition using one eligibility feature each time. Using a previously published database COMPACT as the backend, we designed a scalable method for visual aggregate analysis of clinical trial eligibility features. This method consists of four modules for eligibility feature frequency analysis, query builder, distribution analysis, and visualization, respectively. This method is capable of analyzing (1) frequently used qualitative and quantitative features for recruiting subjects for a selected medical condition, (2) distribution of study enrollment on consecutive value points or value intervals of each quantitative feature, and (3) distribution of studies on the boundary values, permissible value ranges, and value range widths of each feature. All analysis results were visualized using Google Charts API. Five recruited potential users assessed the usefulness of this method for identifying common patterns in any selected eligibility feature for clinical trial participant selection. We implemented this method as a Web-based analytical system called VITTA (Visual Analysis Tool of Clinical Study Target Populations). We illustrated the functionality of VITTA using two sample queries involving quantitative features BMI and HbA1c for conditions "hypertension" and "Type 2 diabetes", respectively. The recruited potential users rated the user-perceived usefulness of VITTA with an average score of 86.4/100. We contributed a novel aggregate analysis method to enable the interrogation of common patterns in quantitative eligibility criteria and the collective target populations of multiple related clinical studies. A larger-scale study is warranted to formally assess the usefulness of VITTA among clinical investigators and sponsors in various therapeutic areas. Copyright © 2015 Elsevier Inc. All rights reserved.

Primary sporadic Burkitt lymphoma of the orbit, clinical characteristics, management, and outcomes: a case study.

PubMed

Bouali, Sofiene; Said, Imed Ben; Yedeas, Mohamed Dahmani; Abderrahmen, Khansa; Maatar, Nidhal; Boubaker, Adnen; Kallel, Jalel; Jemel, Hafedh

2016-03-01

Involvement of the orbit with Burkitt's lymphoma is a very rare presentation of extra-nodal lymphoma. We report a case of a 2-year-old female presented an unusual location of sporadic Burkitt's lymphoma arising in the orbital region. Diagnostic magnetic resonance imagining identified an oval-shaped mass on the lateral rectus of the right orbit that caused dislocation of eyeball, for which she underwent a biopsy from the periorbital swellings. The mass was histologically confirmed as Burkitt's lymphoma, and postoperative aggressive chemotherapy was initiated. We describe clinical diagnosis, histological aspects, radiological features, and current management of this rapidly growing malignant tumor. Because of the rapid progression of Burkitt lymphoma, and considering that it responds well to treatment, early recognition and appropriate management are important factors for survival and to preserve visual function.

Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia

PubMed Central

Minici, Claudia; Gounari, Maria; Übelhart, Rudolf; Scarfò, Lydia; Dühren-von Minden, Marcus; Schneider, Dunja; Tasdogan, Alpaslan; Alkhatib, Alabbas; Agathangelidis, Andreas; Ntoufa, Stavroula; Chiorazzi, Nicholas; Jumaa, Hassan; Stamatopoulos, Kostas; Ghia, Paolo; Degano, Massimo

2017-01-01

Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR–BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones. The diversity of homotypic BcR contacts leading to cell-autonomous signalling reconciles the existence of a shared pathogenic mechanism with the biological and clinical heterogeneity of CLL and offers opportunities for innovative treatment strategies. PMID:28598442

Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes.

PubMed

Nathan, D M; Buse, J B; Davidson, M B; Ferrannini, E; Holman, R R; Sherwin, R; Zinman, B

2009-01-01

The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience.

Femoral diaphyseal stress fracture as the initial presentation of acute leukaemia in an adolescent.

PubMed

Chase, Helen Emily; Pang, Joe Hwong; Sanghrajka, Anish Pradip

2016-06-28

A 14-year-old boy was referred to the orthopaedic clinic by his general practitioner, reporting of a 6-week history of left thigh pain. Clinical examination was unremarkable. Radiographs demonstrated a periosteal reaction at the proximal femur. MRI scans demonstrated a stress fracture of the femur, with no associated sinister features and no evidence of a pathological lesion. As the fracture healed and symptoms improved, the patient became unwell with weight loss, lethargy, chest and jaw pain and fevers. After multiple blood tests over a 25-day period, including five full blood counts and two normal blood films, a third blood film finally demonstrated blasts in keeping with acute leukaemia. We discuss a literature review of musculoskeletal manifestations of leukaemia and the often atypical presentations found. 2016 BMJ Publishing Group Ltd.

What boxing tells us about repetitive head trauma and the brain.

PubMed

Bernick, Charles; Banks, Sarah

2013-01-01

Boxing and other combat sports may serve as a human model to study the effects of repetitive head trauma on brain structure and function. The initial description of what is now known as chronic traumatic encephalopathy (CTE) was reported in boxers in 1928. In the ensuing years, studies examining boxers have described the clinical features of CTE, its relationship to degree of exposure to fighting, and an array of radiologic findings. The field has been hampered by issues related to study design, lack of longitudinal follow-up, and absence of agreed-upon clinical criteria for CTE. A recently launched prospective cohort study of professional fighters, the Professional Fighters Brain Health Study, attempts to overcome some of the problems in studying fighters. Here, we review the cross-sectional results from the first year of the project.

Field study on the epidemiology and pathogenicity of different isolates of bovine Ostertagia spp.

PubMed

Al Saqur, I; Armour, J; Bairden, K; Dunn, A M; Jennings, F W; Murray, M

1982-11-01

The epidemiological features of three different isolates of bovine Ostertagia spp under similar initial levels of larval challenge were compared in the field. Two of the isolates, consisting mainly of Ostertagia ostertagi, and a low proportion of Skrjabinagia lyrata conformed in epidemiological behaviour with those investigated by previous workers, though the worm burdens which established did not give rise to the expected clinical signs. The third isolate behaved in a different way, yielding very high faecal egg counts which were followed by high pasture larval counts, heavy worm burdens and severe clinical disease. This isolate, while consisting mainly of O ostertagi and a few S lyrata, also contained a proportion of O leptospicularis, and it is suggested that this species may influence the dynamics of the host-parasite relationship in bovine ostertagiasis.

Canine eosinophilic folliculitis and furunculosis in three cases.

PubMed

Curtis, C F; Bond, R; Blunden, A S; Thomson, D G; McNeil, P E; Whitbread, T W

1995-03-01

The historical, clinical and histopathological features of three dogs with eosinophilic folliculitis and furunculosis are described. The disease was characterised by the rapid development of pruritic, papular, pustular and ulcerative lesions on the dorsum of the muzzle. Skin lesions were confined to the face in two cases. The third dog had more generalised pustular lesions. Skin biopsy specimens showed marked eosinophil infiltration particularly centred on pilosebaceous units. Dermal collagen necrosis was evident in two cases. Similar facial lesions have previously been described as 'nasal pyoderma'. The three dogs failed to respond to initial antibacterial therapy but showed a rapid clinical response when prednisolone was given orally at doses ranging from 1 to 2.2 mg/kg, in addition to the antibacterial therapy, suggesting that glucocorticoids are indicated for the treatment of eosinophilic folliculitis and furunculosis. The aetiology of the disease was not determined.

Age-associated Pro-inflammatory Remodeling and Functional Phenotype in the Heart and Large Arteries

PubMed Central

Wang, Mingyi; Shah, Ajay M

2015-01-01

The aging population is increasing dramatically. Aging–associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal ventricular-arterial coupling, features that are often clinically silent and thus termed a silent syndrome. These age-related effects are the result of responses initiated by cardiovascular proinflammatory cells. Local proinflammatory signals are coupled between the heart and arteries due to common mechanical and humoral messengers within a closed circulating system. Thus, targeting proinflammatory signaling molecules would be a promising approach to improve age-associated suboptimal ventricular-arterial coupling, a major predisposing factor for the pathogenesis of clinical cardiovascular events such as heart failure. PMID:25665458

Progression of motor and nonmotor features of Parkinson's disease and their response to treatment

PubMed Central

Vu, Thuy C.; Nutt, John G.; Holford, Nicholas H. G.

2012-01-01

AIMS (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments. METHODS Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters. RESULTS Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2–3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED50 of 1237 mg day−1 compared with 7–24 mg day−1 for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression. CONCLUSIONS This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD. PMID:22283961

Association of mammographic image feature change and an increasing risk trend of developing breast cancer: an assessment

NASA Astrophysics Data System (ADS)

Tan, Maxine; Leader, Joseph K.; Liu, Hong; Zheng, Bin

2015-03-01

We recently investigated a new mammographic image feature based risk factor to predict near-term breast cancer risk after a woman has a negative mammographic screening. We hypothesized that unlike the conventional epidemiology-based long-term (or lifetime) risk factors, the mammographic image feature based risk factor value will increase as the time lag between the negative and positive mammography screening decreases. The purpose of this study is to test this hypothesis. From a large and diverse full-field digital mammography (FFDM) image database with 1278 cases, we collected all available sequential FFDM examinations for each case including the "current" and 1 to 3 most recently "prior" examinations. All "prior" examinations were interpreted negative, and "current" ones were either malignant or recalled negative/benign. We computed 92 global mammographic texture and density based features, and included three clinical risk factors (woman's age, family history and subjective breast density BIRADS ratings). On this initial feature set, we applied a fast and accurate Sequential Forward Floating Selection (SFFS) feature selection algorithm to reduce feature dimensionality. The features computed on both mammographic views were individually/ separately trained using two artificial neural network (ANN) classifiers. The classification scores of the two ANNs were then merged with a sequential ANN. The results show that the maximum adjusted odds ratios were 5.59, 7.98, and 15.77 for using the 3rd, 2nd, and 1st "prior" FFDM examinations, respectively, which demonstrates a higher association of mammographic image feature change and an increasing risk trend of developing breast cancer in the near-term after a negative screening.

Acquired bilateral telangiectatic macules: a distinct clinical entity.

PubMed

Park, Ji-Hye; Lee, Dong Jun; Lee, Yoo-Jung; Jang, Yong Hyun; Kang, Hee Young; Kim, You Chan

2014-09-01

We evaluated 13 distinct patients with multiple telangiectatic pigmented macules confined mostly to the upper arms to determine if the clinical and histopathological features of these cases might represent a specific clinical entity. We retrospectively investigated the clinical, histopathologic, and immunohistochemical features of 13 patients with multiple telangiectatic pigmented macules on the upper arms who presented between January 2003 and December 2012. Epidermal pigmentation, melanogenic activity, melanocyte number, vascularity, epidermal thickness, and perivascular mast cell number of the specimens were evaluated. Clinically, the condition favored middle-aged men. On histopathologic examination, the lesional skin showed capillary proliferation and telangiectasia in the upper dermis. Histochemical and immunohistochemical analysis revealed basal hyperpigmentation and increased melanogenic activity in the lesional skin (P < .05). No significant difference in epidermal thickness or mast cell number was observed between the normal perilesional skin and the lesional skin. The clinical and histopathologic features of these lesions were relatively consistent in all patients. In addition, the features are quite distinct from other diseases. Based on clinical and histologic features, we suggest the name acquired bilateral telangiectatic macules for this new entity.

Clinical features and treatment outcomes of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV): A retrospective analysis of 235 patients from a nationwide survey in Japan.

PubMed

Harabuchi, Yasuaki; Kishibe, Kan; Tateyama, Kaori; Morita, Yuka; Yoshida, Naohiro; Kunimoto, Yasuomi; Matsui, Takamichi; Sakaguchi, Hiroshi; Okada, Masahiro; Watanabe, Takeshi; Inagaki, Akira; Kobayashi, Shigeto; Iino, Yukiko; Murakami, Shingo; Takahashi, Haruo; Tono, Tetsuya

2017-01-01

We aimed to analyze clinical features and treatment outcomes of otitis media caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), i.e. otitis media with AAV (OMAAV). This survey was performed between December 2013 and February 2014. The study began with a preliminary survey to 123 otolaryngology institutions in Japan to inquire about their experiences with OMAAV patients during the past 10 years, and was followed by a questionnaire survey to investigate clinical and laboratory findings. OMAAV was defined using the criteria described in the text. Two hundred and thirty-five patients classified as OMAAV were enrolled in this study. They were characterized as follows: (1) disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which did not respond to ordinary treatments such as antibiotics and insertion of tympanic ventilation tubes, followed by progressive hearing loss; (2) predominantly female (73%) and older (median age: 68 years); (3) predominantly myeloperoxidase (MPO)-ANCA-positive (60%), followed by proteinase 3 (PR3)-ANCA-positive (19%) and both ANCAs-negative (16%); (4) frequently observed accompanying facial palsy (36%) and hypertrophic pachymeningitis (28%); and (5) disease often involving lung (35%) and kidney (26%) lesions. Four factors associated with OMAAV were found to be related to an unfavorable clinical course threatening the patient's hearing and/or lives, namely facial palsy, hypertrophic pachymeningitis, both ANCAs-negative phenotype, and disease relapse. The occurrence of hypertrophic pachymeningitis was associated with facial palsy (p < 0.05), both ANCAs-negative phenotype (p < 0.001), and headache (p < 0.001). The administration of corticosteroid together with an immunosuppressant was an independent predicting factor for lack of disease relapse (odds ratio [OR] = 1.90, p = 0.03) and an improvement in hearing loss (OR =2.58, p = 0.0002). Since OMAAV has novel clinical features, the disease may be categorized as a subentity for the classification of AAV.

Hippocampal sclerosis dementia: an amnesic variant of frontotemporal degeneration

PubMed Central

Onyike, Chiadi U.; Pletnikova, Olga; Sloane, Kelly L.; Sullivan, Campbell; Troncoso, Juan C.; Rabins, Peter V.

2013-01-01

OBJECTIVE To describe characteristics of hippocampal sclerosis dementia. METHODS Convenience sample of Hippocampal sclerosis dementia (HSD) recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization. RESULTS The cases showed atrophy and neuronal loss localized to the hippocampus, amygdala and entorrhinal cortex. The majority (79.2%) had amnesia at illness onset, and many (54.2%) showed abnormal conduct and psychiatric disorder. Nearly 42% presented with an amnesic state, and 37.5% presented with amnesia plus abnormal conduct and psychiatric disorder. All eventually developed a behavioral or psychiatric disorder. Disorientation, executive dysfunction, aphasia, agnosia and apraxia were uncommon at onset. Alzheimer disease (AD) was the initial clinical diagnosis in 89% and the final clinical diagnosis in 75%. Diagnosis of frontotemporal dementia (FTD) was uncommon (seen in 8%). CONCLUSION HSD shows pathological characteristics of FTD and clinical features that mimic AD and overlap with FTD. The findings, placed in the context of earlier work, support the proposition that HSD belongs to the FTD family, where it may be identified as an amnesic variant. PMID:24363834

Biomarkers as drug development tools: discovery, validation, qualification and use.

PubMed

Kraus, Virginia B

2018-06-01

The 21st Century Cures Act, approved in the USA in December 2016, has encouraged the establishment of the national Precision Medicine Initiative and the augmentation of efforts to address disease prevention, diagnosis and treatment on the basis of a molecular understanding of disease. The Act adopts into law the formal process, developed by the FDA, of qualification of drug development tools, including biomarkers and clinical outcome assessments, to increase the efficiency of clinical trials and encourage an era of molecular medicine. The FDA and European Medicines Agency (EMA) have developed similar processes for the qualification of biomarkers intended for use as companion diagnostics or for development and regulatory approval of a drug or therapeutic. Biomarkers that are used exclusively for the diagnosis, monitoring or stratification of patients in clinical trials are not subject to regulatory approval, although their qualification can facilitate the conduct of a trial. In this Review, the salient features of biomarker discovery, analytical validation, clinical qualification and utilization are described in order to provide an understanding of the process of biomarker development and, through this understanding, convey an appreciation of their potential advantages and limitations.

Chikungunya: an emerging viral infection with varied clinical presentations in Bangladesh: Reports of seven cases.

PubMed

Rahim, Muhammad Abdur; Uddin, Khwaja Nazim

2017-08-15

Chikungunya is an emerging and rapidly spreading viral infection in many parts of the world including Bangladesh. It shares many epidemiological and clinical characteristics with dengue. So, a sound knowledge is required for its detection and differentiation from dengue, specially in endemic regions. We present seven confirmed cases of chikungunya having different clinical presentations occurring among middle aged males and females from different socio-economic background in Dhaka city, the capital of Bangladesh. All patients had fever and aches and pains. Less common features were rash, diarrhea, vomiting and altered liver biochemistry. Dengue was excluded in six patients. Paracetamol remained the mainstay of treatment during febrile periods, but over 50% of the patients had prolonged joint symptoms requiring non-steroidal anti-inflammatory drugs. In spite of being a self-limiting disease, chikungunya may have different presentations and a protracted clinical course. During the febrile episode, exclusion of dengue is equally important. Physicians should be aware of the condition and public health initiatives are necessary to break the disease transmission.