N-terminal pro-B-type natriuretic peptide is an independent predictor of outcome in an unselected cohort of critically ill patients.

PubMed

Meyer, Brigitte; Huelsmann, Martin; Wexberg, Paul; Delle Karth, Georg; Berger, Rudolf; Moertl, Deddo; Szekeres, Thomas; Pacher, Richard; Heinz, Gottfried

2007-10-01

Natriuretic peptides emerged during recent years as potent prognostic markers in patients with heart failure and acute myocardial infarction. In addition, natriuretic peptides show strong predictive value in patients with pulmonary embolism, sepsis, renal failure, and shock. The present study tests the prognostic information of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in an unselected cohort of critically ill patients. Prospective, observational study. A tertiary intensive care unit in a university hospital. A total of 289 consecutive patients admitted to the intensive care unit during a 16-month period with the following data: age 64 +/- 14 yrs, male n = 191, Simplified Acute Physiology Score II of 52 +/- 24, mechanical ventilation n = 180 (62%), vasopressors n = 179 (62%), renal failure n = 24 (8%). None. Plasma NT-pro-BNP samples (Roche Diagnostics) were obtained on intensive care unit admission. Data are given as median [range]. Intensive care unit survivors had significantly lower NT-pro-BNP values compared with intensive care unit nonsurvivors (3394 [24-35,000] vs. 6776 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). Hospital survivors were characterized by significantly lower NT-pro-BNP values (2656 [24-35,000] vs. 8390 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). NT-pro-BNP levels were not significantly different in patients with primary cardiac diagnosis compared with those with a noncardiac admission diagnosis (4794 [26-35,000], n = 202 vs. 3349 [24-35,000], n = 87, cardiac vs. noncardiac, respectively, p = .28). In a logistic regression model, Simplified Acute Physiology Score II and NT-pro-BNP were independently associated with hospital survival (chi = 35.6, p = .0001 and chi = 11.3, p = .0008, Simplified Acute Physiology Score II and NT-pro-BNP, respectively). Areas under the receiver operating characteristic curves of NT-pro-BNP and Simplified Acute Physiology Score II were not statistically significant different regarding the prediction of outcome. NT-pro-BNP on admission is an independent prognostic marker of outcome in an unselected cohort of critically ill patients. A single measurement of NT-pro-BNP might facilitate triage of emergency and intensive care unit patients.

Impact of iso-osmolar versus low-osmolar contrast agents on contrast-induced nephropathy and tissue reperfusion in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the Contrast Media and Nephrotoxicity Following Primary Angioplasty for Acute Myocardial Infarction [CONTRAST-AMI] Trial).

PubMed

Bolognese, Leonardo; Falsini, Giovanni; Schwenke, Carsten; Grotti, Simone; Limbruno, Ugo; Liistro, Francesco; Carrera, Arcangelo; Angioli, Paolo; Picchi, Andrea; Ducci, Kenneth; Pierli, Carlo

2012-01-01

Conflicting data have been reported on the effects of low-osmolar and iso-osmolar contrast media on contrast-induced acute kidney injury (CI-AKI). In particular, no clinical trial has yet focused on the effect of contemporary contrast media on CI-AKI, epicardial flow, and microcirculatory function in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention. The Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty for Acute Myocardial Infarction (CONTRAST-AMI) trial is a prospective, randomized, single-blind, parallel-group, noninferiority study aiming to evaluate the effects of the low-osmolar contrast medium iopromide compared to the iso-osmolar agent iodixanol on CI-AKI and tissue-level perfusion in patients with ST-segment elevation acute myocardial infarction. Four hundred seventy-five consecutive, unselected patients who underwent primary percutaneous coronary intervention were randomized to iopromide (n = 239) or iodixanol (n = 236). All patients received high-dose N-acetylcysteine and hydration. The primary end point was the proportion of patients with serum creatinine (sCr) increases ≥25% from baseline to 72 hours. Secondary end points were Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, increase in sCr ≥50%, increase in sCr ≥0.5 or ≥1 mg/dl, and 1-month major adverse cardiac events. The primary end point occurred in 10% of the iopromide group and in 13% of the iodixanol group (95% confidence interval -9% to 3%, p for noninferiority = 0.0002). A TIMI myocardial perfusion grade of 0 or 1 was present in 14% of patients in the 2 groups. No differences between the 2 groups were found in any of the secondary analyses of sCr increase. No significant difference in 1-month major adverse cardiac events was found (8% vs 6%, p = 0.37). In conclusion, in a population of unselected patients with ST-segment elevation acute myocardial infarction who underwent primary percutaneous coronary intervention, iopromide was not inferior to iodixanol in the occurrence of CI-AKI; no significant differences were found in terms of tissue-level reperfusion and major adverse cardiac events between the 2 contrast agents. Copyright © 2012 Elsevier Inc. All rights reserved.

Veress needle insertion into the left hypochondrium for creation of pneumoperitoneum: diagnostic value of tests to determine the position of the needle in unselected patients.

PubMed

Becker, Otávio Monteiro; Azevedo, João Luiz Moreira Coutinho; de Azevedo, Otávio Cansanção; Hypólito, Octávio Henrique Mendes; Miyahira, Susana Abe; Miguel, Gustavo Peixoto Soares; Machado, Afonso Cesar Cabral Guedes

2011-01-01

To assess the effectiveness of the Veress needle puncture in the left hypochondrium and the accuracy of the tests described for the intraperitoneal correct positioning of the tip of the Veress needle in an unselected population. Ninetyone patients consecutively scheduled for Videolaparoscopy had the abdominal wall punctured in the left hypochondrium. There were no exclusion criteria. The patients received general anesthesia and mechanical ventilation according to the protocol. After puncturing five tests were used to confirm the positioning of the needle tip within the peritoneal cavity: aspiration test--AT; resistance to infusion--Pres; recovery of the infused fluid--Prec, dripping test--DT, and test of initial intraperitoneal pressure--IIPP. The test results were compared with results from literature for groups with defined exclusion criteria. The results were used for calculating sensitivity (S) specificity (E), positive predictive value (PPV) and negative predictive value (NPV). Inferential statistical methods were used to analyze the findings. There were 13 failures. AT had E = 100% and NPV 100%. Pres had S = 100%, E = 0; PPV = 85.71%; NPV does not apply. Prec: S = 100%, E = 53.84%, PPV = 92.85%, NPV = 100%. DT: S = 100%, E = 61.53%, PPV = 93.97% NPV 100%. In IIPP, S, E, PPV and NPV were 100%. The puncture in the left hypochondrium is effective and the performed tests guide the surgeon regardless of sex, BMI, or previous laparotomy.

Elevated carboxyhemoglobin: sources of carbon monoxide exposure.

PubMed

Buchelli Ramirez, Herminia; Fernández Alvarez, Ramón; Rubinos Cuadrado, Gemma; Martinez Gonzalez, Cristina; Rodriguez Jerez, Francisco; Casan Clara, Pere

2014-11-01

Inhalation of carbon monoxide (CO) can result in poisoning, with symptoms ranging from mild and nonspecific to severe, or even death. CO poisoning is often underdiagnosed because exposure to low concentrations goes unnoticed, and threshold values for normal carboxyhemoglobin vary according to different authors. The aim of our study was to analyze carboxyhemoglobin (COHb) levels in an unselected population and detect sources of CO exposure In a cross-sectional descriptive study, we analyzed consecutive arterial blood gas levels processed in our laboratory. We selected those with COHb≥2.5% in nonsmokers and ≥5% in smokers. In these cases a structured telephone interview was conducted. Elevated levels of COHb were found in 64 (20%) of 306 initial determinations. Of these, data from 51 subjects aged 65±12 years, 31 (60%) of which were men, were obtained. Mean COHb was 4.0%. Forty patients (78%) were non-smokers with mean COHb of 3.2%, and 11 were smokers with COHb of 6.7%. In 45 patients (88.2%) we detected exposure to at least one source of ambient CO other than cigarette smoke. A significant proportion of individuals from an unselected sample had elevated levels of COHb. The main sources of CO exposure were probably the home, so this possibility should be explored. The population should be warned about the risks and encouraged to take preventive measures. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

A Follow-Up Study of Mortality, Health Conditions and Associated Disabilities of People with Intellectual Disabilities in a Swedish County

ERIC Educational Resources Information Center

Gustavson, K.-H.; Umb-Carlsson, O.; Sonnander, K.

2005-01-01

Background: In the planning of services and health care for individuals with intellectual disability (ID), information is needed on the special requirements for habilitation and medical service and associated disabilities. Material and Methods: An unselected consecutive series of 82 adult persons with ID was studied. The medical examination…

Analytical evaluation of point of care cTnT and clinical performances in an unselected population as compared with central laboratory highly sensitive cTnT.

PubMed

Dupuy, Anne Marie; Sebbane, Mustapha; Roubille, François; Coste, Thibault; Bargnoux, Anne Sophie; Badiou, Stéphanie; Kuster, Nils; Cristol, Jean Paul

2015-03-01

To report the analytical performances of the Radiometer AQT90 FLEX® cTnT assay (Neuilly-Plaisance, France) and to evaluate the concordance with hs-cTnT results from central laboratory for the diagnosis of acute myocardial infarction (AMI) at baseline and during a short follow-up among unselected patients admitted in emergency room or cardiology department. Analytical performances of AQT90 FLEX® cTnT immunoassay included imprecision study with determination of a coefficient of variation at 10% and 20%, linearity, and limit of detection. The concordance study was based on samples obtained from 170 consecutive patients with chest pain suggestive of acute coronary syndrome (ACS) admitted in the emergency room or cardiology department. The kinetic study (within 62 additional samples 3h later) was based on absolute delta criterion and the combination of relative change of 30% with absolute change of 7ng/L. The cTnT assay from Radiometer was evaluated as clinically usable, although less sensitive than the Roche hs-cTnT assay as demonstrated by the concordance and the kinetic studies. In non-selected population, the cTnT AQT Flex© assay on AQT90© with kinetic change at 3h, provides similar clinical classification of patients, particularly for AMI group as compared to central laboratory hs-cTnT assay and could be suitable for clinical use. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Referral Bias in Defining the Phenotype and Prevalence of Obesity in Polycystic Ovary Syndrome

PubMed Central

Ezeh, Uche; Yildiz, Bulent O.

2013-01-01

Background: The described phenotype of the polycystic ovary syndrome (PCOS) has been primarily based on findings in a referred (self or otherwise) population. It is possible that the phenotype of PCOS would be different if the disorder were to be detected and studied in its natural (unbiased) state. Objective: Our objective was to compare the phenotype of PCOS detected in an unselected population with that identified in a referral population. Participants: Participants included 292 PCOS patients identified at a tertiary care outpatient facility (referral PCOS) and 64 PCOS women (unselected PCOS) identified through the screening of a population of 668 seeking a pre-employment physical. Among the women undergoing a pre-employment physical, 563 did not demonstrate features of the disorder (unselected controls). All PCOS subjects met the National Institutes of Health 1990 criteria for the disorder. Main Outcome Measures: We estimated prevalence of obesity and severity of disease burden. Results: Referral PCOS subjects had greater mean body mass index and hirsutism score and higher degrees of hyperandrogenemia, were more likely to be non-Hispanic White (83.90%), and demonstrated a more severe PCOS subphenotype than unselected PCOS or unselected controls. The prevalence of obesity and severe obesity in referral PCOS was 2.3 and 2.5 times greater than estimates of the same in unselected PCOS and 2.2 and 3.8 times greater than estimates in unselected controls, respectively. Alternatively, unselected PCOS subjects had a prevalence of obesity and severe obesity and a mean body mass index similar to those of the general population from which they were derived. Conclusion: The phenotype of PCOS, including the racial/ethnic mix, severity of presentation, and rate of obesity, is affected significantly by whether the PCOS subject arises from a referral population or through unselected screening, likely reflecting the degree of patient concern and awareness and access to healthcare. PMID:23539721

Impact of the introduction of a standardised ICD programming protocol: real-world data from a single centre.

PubMed

Sunderland, Nicholas; Kaura, Amit; Li, Anthony; Kamdar, Ravi; Petzer, Ed; Dhillon, Para; Murgatroyd, Francis; Scott, Paul A

2016-09-01

Randomised trials have shown that empiric ICD programming, using long detection times and high detection zones, reduces device therapy in ICD recipients. However, there is less data on its effectiveness in a "real-world" setting, especially secondary prevention patients. Our aim was to evaluate the introduction of a standardised programming protocol in a real-world setting of unselected ICD recipients. We analysed 270 consecutive ICD recipients implanted in a single centre-135 implanted prior to protocol implementation (physician-led group) and 135 after (standardised group). The protocol included long arrhythmia detection times (30/40 or equivalent) and high rate detection zones (primary prevention lower treatment zone 200 bpm). Programming in the physician-led group was at the discretion of the implanter. The primary endpoint was time-to-any therapy (ATP or shocks). Secondary endpoints were time-to-inappropriate therapy and time-to-appropriate therapy. The safety endpoints were syncopal episodes, hospital admissions and death. At 12 months follow-up, 47 patients had received any ICD therapy (physician-led group, n = 31 vs. standardised group, n = 16). There was a 47 % risk reduction in any device therapy (p = 0.04) and an 86 % risk reduction in inappropriate therapy (p = 0.009) in the standardised compared to the physician-led group. There was a non-significant 30 % risk reduction in appropriate therapy (p = 0.32). Results were consistent across primary and secondary prevention patients. There were no significant differences in the rates of syncope, hospitalisation, and death. In unselected patients in a real-world setting, introduction of a standardised programming protocol, using long detection times and high detection zones, significantly reduces the burden of ICD therapy without an increase in adverse outcomes.

Electrocardiographic screening for emphysema: the frontal plane P axis.

PubMed

Baljepally, R; Spodick, D H

1999-03-01

Because the most characteristic and sensitive electrocardiographic (ECG) correlate of pulmonary emphysema in adults is verticalization of the frontal plane P-wave vector (P axis), we investigated its strength as a lone criterion to screen for obstructive pulmonary disease (OPD) in an adult hospital population. In all, 954 consecutive unselected ECGs were required to yield 100 with P axis > or = +70 degrees (unequivocally negative P in a VL during sinus rhythm) and pulmonary function tests. and 100 with P axis < or = +50 degrees (unequivocally positive P-aVL). Obstructive pulmonary disease by both pulmonary function test and clinical criteria was present in 89 of 100 patients with vertical P axes and 4 of 100 patients without OPD. The high sensitivity (89% for this series) and high specificity (96%) makes vertical P axis a useful screening criterion. Its at-a-glance simplicity makes it "user-friendly."

RAD50 germline mutations are associated with poor survival in BRCA1/2-negative breast cancer patients.

PubMed

Fan, Cong; Zhang, Juan; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

2018-05-04

RAD50 is a highly conserved DNA double-strand break (DSB) repair gene. However, the associations between RAD50 germline mutations and the survival and risk of breast cancer have not been fully elucidated. Here, we aimed to investigate the clinical impact of RAD50 germline mutations in a large cohort of unselected breast cancer patients. In this study, RAD50 germline mutations were determined using next-generation sequencing in 7657 consecutive unselected breast cancer patients without BRCA1/2 mutations. We also screened for RAD50 recurrent mutations (L719fs, K994fs, and H1269fs) in 5000 healthy controls using Sanger sequencing. We found that 26 out of 7657 (0.34%) patients had RAD50 pathogenic mutations, and 16 patients carried one of the three recurrent mutations (L719fs, n=6 cases; K994fs, n=5 cases; and H1269fs, n=5 cases); the recurrent mutation rate was 0.21%. The frequency of the three recurrent mutations in the 5000 healthy controls was 0.18% (9/5000). These mutations did not confer an increased risk of breast cancer in the studied patients [odds ratios (OR), 1.16; 95% confidence interval (CI), 0.51-2.63; P = 0.72]. Nevertheless, multivariate analysis revealed that RAD50 pathogenic mutations were an independent unfavourable predictor of recurrence-free survival (RFS) [adjusted hazard ratio (HR) 2.66; 95% CI, 1.18-5.98; P=0.018] and disease-specific survival (DSS) (adjusted HR 4.36; 95% CI, 1.58-12.03; P=0.004) in the entire study cohort. Our study suggested that RAD50 germline mutations are not associated with an increased risk of breast cancer, but patients with RAD50 germline mutations have unfavourable survival compared with patients without these mutations. This article is protected by copyright. All rights reserved. © 2018 UICC.

Sex-related differences after contemporary primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

PubMed

Barthélémy, Olivier; Degrell, Philippe; Berman, Emmanuel; Kerneis, Mathieu; Petroni, Thibaut; Silvain, Johanne; Payot, Laurent; Choussat, Remi; Collet, Jean-Philippe; Helft, Gerard; Montalescot, Gilles; Le Feuvre, Claude

2015-01-01

Whether outcomes differ for women and men after percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains controversial. To compare 1-year outcomes after primary PCI in women and men with STEMI, matched for age and diabetes. Consecutive women with STEMI of<24 hours' duration referred (August 2007 to January 2011) for primary PCI were compared with men matched for age and diabetes. Rates of all-cause mortality, target vessel revascularization (TVR) and major cardiovascular and cerebrovascular events (MACCE) (death/myocardial infarction/stroke) were assessed at 1 year. Among 775 consecutive patients, 182 (23.5%) women were compared with 182 matched men. Mean age was 69±15 years, 18% had diabetes. Patient characteristics were similar, except for lower creatinine clearance (73±41 vs 82±38 μmol/L; P=0.041), more cardiogenic shock (14.8% vs 6.6%; P=0.017) and less radial PCI (81.3% vs 90.1%; P=0.024) in women. Rates of 1-year death (22.7% vs 18.1%), TVR (8.3% vs 6.0%) and MACCE (24.3% vs 20.9%) were not statistically different in women (P>0.05 for all). After exclusion of patients with shock (10.7%) and out-of-hospital cardiac arrest (6.6%), death rates were even more similar (11.3% vs 11.8%; P=0.10). Female sex was not independently associated with death (odds ratio 1.01, 95% confidence interval 0.55-1.87; P=0.97). In our consecutive unselected patient population, women had similar 1-year outcomes to men matched for age and diabetes, after contemporary primary PCI for STEMI, despite having a higher risk profile at baseline. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Additional diagnostic and prognostic value of copeptin ultra-sensitive for diagnosis of non-ST-elevation myocardial infarction in older patients presenting to the emergency department.

PubMed

Bahrmann, Philipp; Bahrmann, Anke; Breithardt, Ole-A; Daniel, Werner G; Christ, Michael; Sieber, Cornel C; Bertsch, Thomas

2013-06-01

Identifying older patients with non-ST- elevation myocardial infarction (NSTEMI) within the very large proportion with elevated high-sensitive cardiac troponin T (hs-cTnT) is a diagnostic challenge because they often present without clear symptoms or electrocardiographic features of acute coronary syndrome to the emergency department (ED). We prospectively investigated the diagnostic and prognostic performance of copeptin ultra-sensitive (copeptin-us) and hs-cTnT compared to hs-cTnT alone for NSTEMI at prespecified cut-offs in unselected older patients. We consecutively enrolled 306 non-surgical patients ≥70 years presenting to the ED. In addition to clinical examination, copeptin-us and hs-cTnT were measured at admission. Two cardiologists independently adjudicated the final diagnosis of NSTEMI after reviewing all available data. All patients were followed up for cardiovascular-related death within the following 12 months. NSTEMI was diagnosed in 38 (12%) patients (age 81±6 years). The combination of copeptin-us ≥14 pmol/L and hs-cTnT ≥0.014 µg/L compared to hs-cTnT ≥0.014 µg/L alone had a positive predictive value of 21% vs. 19% to rule in NSTEMI. The combination of copeptin-us <14 pmol/L and hs-cTnT <0.014 µg/L compared to hs-cTnT <0.014 µg/L alone had a negative predictive value of 100% vs. 99% to rule out NSTEMI. Hs-cTnT ≥0.014 µg/L alone was significantly associated with outcome. When copeptin-us ≥14 pmol/L was added, the net reclassification improvement for outcome was not significant (p=0.809). In unselected older patients presenting to the ED, the additional use of copeptin-us at predefined cut-offs may help to reliably rule out NSTEMI but may not help to increase predicted risk for outcome compared to hs-cTnT alone.

Validation of the GRACE Risk score for hospital mortality in patients with acute coronary syndrome in the Arab Middle East.

PubMed

Yusufali, Afzalhussein; Zubaid, Mohammad; Al-Zakwani, Ibrahim; Alsheikh-Ali, Alawi A; Al-Mallah, Mouaz H; Al Suwaidi, Jassim; AlMahmeed, Wael; Rashed, Wafa; Sulaiman, Kadhim; Amin, Haitham

2011-07-01

Our objective was to validate the Global Registry of Acute Coronary Events (GRACE) risk score for in-hospital mortality in a Middle Eastern acute coronary syndrome (ACS) population enrolled in the Gulf Registry of Acute Coronary Events (Gulf RACE). Out of 8176, unselected, consecutive patients with ACS, during 6 months in 2006 and 2007 from 63 hospitals in 6 Arab countries in the Middle East Gulf region, 7709 (94.3%) with available data were included. The main outcome measures were discriminatory performance (using C-index) and calibration of the GRACE risk score (in-hospital mortality predicted by GRACE risk score versus the actual mortality). In-hospital mortality in the Gulf RACE was 3.09% (n = 238). The discriminatory performance of the GRACE risk scores in the Gulf RACE was good overall (C-index = 0.86). Observed and predicted risk corresponded well in each stratum of risk of in-hospital mortality. This suggests its suitability for clinical use in this patient population.

Does addition of low-level laser therapy (LLLT) in conservative care of knee arthritis successfully postpone the need for joint replacement?

PubMed

Ip, David

2015-12-01

The current study evaluates whether the addition of low-level laser therapy into standard conventional physical therapy in elderly with bilateral symptomatic tri-compartmental knee arthritis can successfully postpone the need for joint replacement surgery. A prospective randomized cohort study of 100 consecutive unselected elderly patients with bilateral symptomatic knee arthritis with each knee randomized to receive either treatment protocol A consisting of conventional physical therapy or protocol B which is the same as protocol A with added low-level laser therapy. The mean follow-up was 6 years. Treatment failure was defined as breakthrough pain which necessitated joint replacement surgery. After a follow-up of 6 years, patients clearly benefited from treatment with protocol B as only one knee needed joint replacement surgery, while nine patients treated with protocol A needed surgery (p < 0.05). We conclude low-level laser therapy should be incorporated into standard conservative treatment protocol for symptomatic knee arthritis.

Short-term clinical outcomes after off-pump coronary artery bypass grafting at a single Veterans Affairs Medical Center.

PubMed

Lushaj, Entela B; Schreiner, Athanasia; Jonuzi, Besa; Badami, Abbasali; DeOliveira, Nilto; Lozonschi, Lucian

2016-05-17

We retrospectively assessed the outcomes after coronary revascularization at a single Veterans Affairs Medical Center when a strategy of assigning higher risk patients to off-pump coronary artery bypass grafting (CABG) was employed. Over a 5 year period all consecutive patients that underwent CABG at our VA Medical Center were assigned to a surgeon who either performs the CABG exclusively off-pump or to one who performed the CABG on-pump. The higher risk patients were assigned preferentially for off-pump revascularization. VASQIP (VA Hospitals Surgical Quality Improvement Program) data between 10/2007 and 12/2012 were retrospectively reviewed at our VA Medical Center and the short term outcomes were assessed. A total of 252 consecutive patients underwent off-pump CABG (n = 170) and on-pump CABG (n = 82). There were significantly more patients with low LVEF (<45 %; p = 0.008) and cerebrovascular disease in the off-pump group (p = 0.024). The number of patients smoking at the time of surgery was significantly higher in the off-pump group (p = 0.002) as well. The 30-day composite morbidity and mortality was 6 % for all CABG patients and significantly lower with off-pump vs. on-pump CABG (3.5 % vs. 11 %; p = 0.019). There were no conversions from off-pump to on-pump surgery. A selective strategy to direct higher risk patients towards an off-pump revascularization yielded favorable outcomes in an unselected veteran population treated at a single VA Medical Center over a 5 year period.

Predisposing cardiac conditions, interventional procedures, and antibiotic prophylaxis among patients with infective endocarditis.

PubMed

Chirillo, Fabio; Faggiano, Pompilio; Cecconi, Moreno; Moreo, Antonella; Squeri, Angelo; Gaddi, Oscar; Cecchi, Enrico

2016-09-01

Efficacy and safety of antibiotic prophylaxis (AP) for prevention of infective endocarditis (IE) in patients with predisposing cardiac condition (PCC) undergoing invasive procedures is still debated. We sought to assess the prevalence of PCC, the type of interventional procedures preceding the onset of symptoms, and the usefulness of AP in a large cohort of consecutive patients with definite IE. We examined 677 (median age 65.34 years; male 492 [73%]) consecutive patients with IE enrolled from July 2007 through 2010 into the Italian Registry of Infective Endocarditis. Predisposing cardiac condition was present in 341 patients (50%).Thirty-two patients (4.7%) underwent dental procedures. Of 20 patients with PCC undergoing dental procedure, 13 had assumed AP. Viridans group streptococci were isolated from blood cultures in 8 of 20 patients with PCC and prior dental procedure. Nondental procedures preceded IE in 139 patients (21%). They were significantly older and had more comordibities compared with patients undergoing dental procedures. Predisposing cardiac condition was identified in 91 patients. Perioperative antimicrobial prophylaxis was administered to 67 patients. Staphylococcus aureus was the most frequent causative agent. Cardiac surgery was necessary in 85 patients (20 with prior dental and 65 with nondental procedure). Surgical mortality (12% vs 0%, P = .03) and hospital mortality (23% vs 3%, P = .001) were significantly larger among patients with nondental procedures. In a large unselected cohort of patients with IE, the incidence of preceding dental procedures was minimal. The number of cases potentially preventable by means of AP was negligible. Nondental procedures were more frequent than dental procedures and were correlated with poorer prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Mast, Mirjam E., E-mail: m.mast@mchaaglanden.nl; Heijenbrok, Mark W.; Petoukhova, Anna L.

Purpose: Breast cancer radiotherapy has been associated with an increased risk of cardiac toxicity. However, no data are available on the probability of developing coronary artery disease (CAD) in breast cancer patients when compared with healthy women. Therefore, baseline coronary artery calcium (CAC) scores, as an accepted tool to predict CAD, were determined and compared with the CAC scores of a healthy, asymptomatic cohort, the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Methods and Materials: Eighty consecutive patients with ductal carcinoma in situ or infiltrative breast cancer referred for radiotherapy after breast-conserving surgery were included in our study. Their cardiovascular riskmore » profile was registered, and a 64 multislice CT scan was performed. The CAC scores of an unselected (Caucasian only) Radiotherapy Centre West (RCWEST) cohort, as well as of those of a selected (comorbidity and race adjusted) RCWEST cohort, were determined. The scores of both cohorts were compared with those of the female (Caucasian only) MESA cohort. Results: For the unselected RCWEST cohort (n = 62) we found significant (p < .01) higher scores for women in the 55-64 age category compared with those of the MESA cohort. In the selected cohort (n = 55) the CAC scores of the women in the age category 55-64 were significantly (p = .02) higher compared with the MESA cohort. No significant differences were noted in the other age categories. Conclusion: Both cohorts revealed that CAC scores in the 55-64 age category were significantly higher than the CAC scores in the asymptomatic (female) MESA population. These data suggest that breast cancer patients bear a higher risk of developing coronary heart disease before the start of radiotherapy. Therefore, measures to decrease cardiac dose further in breast cancer radiotherapy are even more important.« less

Prevalence, awareness, treatment, and control rate of hypertension in HIV-infected patients: the HIV-HY study.

PubMed

De Socio, Giuseppe Vittorio; Ricci, Elena; Maggi, Paolo; Parruti, Giustino; Pucci, Giacomo; Di Biagio, Antonio; Calza, Leonardo; Orofino, Giancarlo; Carenzi, Laura; Cecchini, Enisia; Madeddu, Giordano; Quirino, Tiziana; Schillaci, Giuseppe

2014-02-01

We aimed to assess the prevalence of hypertension in an unselected human immunodeficiency virus (HIV)-infected population and to identify factors associated with hypertension prevalence, treatment, and control. We used a multicenter, cross-sectional, nationwide study that sampled 1,182 unselected, consecutive, HIV-infected patients. Office blood pressure was accurately measured with standard procedures. Patients were 71% men and 92% white, with a median age of 47 years (range = 18-78); 6% were antiretroviral treatment naive. The overall prevalence of hypertension was 29.3%; high-normal pressure accounted for an additional 12.3%. Among hypertensive subjects, 64.9% were aware of their hypertensive condition, 52.9% were treated, and 33.0% were controlled (blood pressure < 140/90 mm Hg). Blood pressure-lowering medications were used in monotherapy in 54.3% of the subjects. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were the most frequently used drugs (76.1%: monotherapy = 39.1%, combination treatment = 37.0%). In multivariable regression models, hypertension was independently predicted by traditional risk factors, including age ≥50 years, male sex, family history of cardiovascular disease, body mass index ≥25 kg/m2, previous cardiovascular events, diabetes, central obesity, and metabolic syndrome, as well as by duration of HIV infection, duration of antiretroviral therapy, and nadir CD4+ T-cell count <200/μl. The choice of protease inhibitors vs. nonnucleoside reverse transcriptase inhibitors as a third antiretroviral drug was irrelevant. Hypertension affects nearly 30% of HIV adult outpatients in Italy. More than one-third of the hypertensive subjects are unaware of their condition, and more than two-thirds are uncontrolled. A higher level of attention to the diagnosis and treatment of hypertension is mandatory in this setting.

Individual polyp detection rate in routine daily endoscopy practice depends on case-mix.

PubMed

Loffeld, R J L F; Liberov, B; Dekkers, P E P

2015-07-01

The adenoma detection rate (ADR), a marker of endoscopic quality, is confounded by selection bias. It is not known what the ADR is in normal daily practice. To study the polyp detection rate (PDR) in different endoscopists in the course of years. All consecutive endoscopies of the colon done in 11 years were included. Endoscopies in the regular surveillance programme after polyp removal and after surgery because of colorectal cancer or diverticular disease were scored separately. The number of yearly procedures per endoscopist and presence of polyps, anastomoses, surveillance and cancer were noted. In the period of 11 years, 14,908 consecutive endoscopies of colon and rectum were done by four endoscopists. Two endoscopists had a significantly lower PDR than the other two (p < 0.001), these two had the longest careers in endoscopy. The two younger endoscopists did significantly less often procedures in patients with anastomoses and because of surveillance (p < 0.001, respectively). One endoscopist detected significantly less colorectal cancers than the other three endoscopists (p < 0.001). This study presents the PDR in normal routine daily endoscopy practice. It can be concluded that the PDR, implicating the ADR, in unselected patients can be lower in individual endoscopists than recommended in the literature. This highly depends on the case-mix of patients presented for endoscopy. This result debates the use of the ADR as quality indicator for individual endoscopists.

Prevalence of Obstructive Sleep Apnea in Patients with Chronic Wounds

PubMed Central

Patt, Brian T.; Jarjoura, David; Lambert, Lynn; Roy, Sashwati; Gordillo, Gayle; Schlanger, Richard; Sen, Chandan K.; Khayat, Rami N.

2010-01-01

Study Objectives: Chronic non-healing wounds are a major human and economic burden. Obstructive sleep apnea (OSA) is prevalent in patients with obesity, diabetes, aging, and cardiovascular disease, all of which are risk factors for chronic wounds. We hypothesized that OSA would have more prevalence in patients of a wound center than the general middle-aged population. Methods: Consecutive patients of the Ohio State University Comprehensive Wound Center (CWC) were surveyed with the Berlin and Epworth questionnaires. In the second stage of the protocol, 50 consecutive unselected CWC patients with lower extremity wounds underwent home sleep studies. Results: In 249 patients of the CWC who underwent the survey study, OSA had been previously diagnosed in only 22%. The prevalence of high-risk status based on questionnaires for OSA was 46% (95% CI 40%, 52%). In the 50 patients who underwent home sleep studies, and using an apnea hypopnea index of 15 events per hour, the prevalence of OSA was 57% (95% CI 42%, 71%). There was no difference between the Berlin questionnaire score and weight between patients with OSA and those without. Conclusions: The prevalence of OSA in patients with chronic wounds exceeds the estimated prevalence of OSA in the general middle aged population. This study identifies a previously unrecognized population with high risk for OSA. Commonly used questionnaires were not sufficiently sensitive for the detection of high risk status for OSA in this patient population. Citation: Patt BT; Jarjoura D; Lambert L; Roy S; Gordillo G; Schlanger R; Sen CK; Khayat RN. Prevalence of obstructive sleep apnea in patients with chronic wounds. J Clin Sleep Med 2010;6(6):541-544. PMID:21206743

Gastro-oesophageal reflux in patients with chronic rhino-sinusitis investigated with multichannel impedance - pH monitoring.

PubMed

Katle, E J; Hatlebakk, J G; Grimstad, T; Kvaløy, J T; Steinsvåg, S K

2017-03-01

The pathophysiology of chronic rhinosinusitis (CRS) is unclear. It has been discussed for decades whether gastro-oesophageal reflux (GOR) may be a contributing factor for some patients. The aim of the present study was to evaluate the level of GOR in an unselected group of patients with CRS using multichannel impedance-pH monitoring. Consecutive patients with CRS diagnosed using the EPOS2012 criteria, completed questionnaires on GOR symptoms and were offered 24-h multichannel intraluminal impedance (MII)-pH monitoring. The results were compared with a group of healthy controls. Forty-six patients completed MII-pH-monitoring and were compared with 45 control subjects, with comparable age and gender distributions. The median number of reflux episodes in the patients was 56.5 compared with 33 in controls, while, the numbers of proximal reflux episodes was 27.5 versus 3, respectively. Thirty nine patients had abnormal pH-impedance recordings compared with five controls. The CRS patients had significantly higher incidences of gastro-oesophageal reflux compared with asymptomatic controls. The results of this study suggest that GOR may be a causative or contributing factor of CRS.

Lyral has been included in the patch test standard series in Germany.

PubMed

Geier, Johannes; Brasch, Jochen; Schnuch, Axel; Lessmann, Holger; Pirker, Claudia; Frosch, Peter J

2002-05-01

Lyral 5% pet. was tested in 3245 consecutive patch test patients in 20 departments of dermatology in order (i) to check the diagnostic quality of this patch test preparation, (ii) to examine concomitant reactions to Lyral and fragrance mix (FM), and (iii) to assess the frequency of contact allergy to Lyral in an unselected patch test population of German dermatological clinics. 62 patients reacted to Lyral, i.e. 1.9%. One third of the positive reactions were + + and + + +. The reaction index was 0.27. Thus, the test preparation can be regarded a good diagnostic tool. Lyral and fragrance mix (FM) were tested in parallel in 3185 patients. Of these, 300 (9.4%) reacted to FM, and 59 (1.9%) to Lyral. In 40 patients, positive reactions to both occurred, which is 13.3% of those reacting to FM, and 67.8% of those reacting to Lyral. So the concordance of positive test reactions to Lyral and FM was only slight. Based on these results, the German Contact Dermatitis Research Group (DKG) decided to add Lyral 5% pet. to the standard series.

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Almstedt, Katrin; Heimes, Anne-Sophie; Makris, Georgios-Marios; Weyer, Veronika; Schmidt, Marcus

2016-09-01

New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.

Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer

PubMed Central

Couch, Fergus J.; Hart, Steven N.; Sharma, Priyanka; Toland, Amanda Ewart; Wang, Xianshu; Miron, Penelope; Olson, Janet E.; Godwin, Andrew K.; Pankratz, V. Shane; Olswold, Curtis; Slettedahl, Seth; Hallberg, Emily; Guidugli, Lucia; Davila, Jaime I.; Beckmann, Matthias W.; Janni, Wolfgang; Rack, Brigitte; Ekici, Arif B.; Slamon, Dennis J.; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Fountzilas, George; Pelttari, Liisa M.; Tapper, William J.; Durcan, Lorraine; Cross, Simon S.; Pilarski, Robert; Shapiro, Charles L.; Klemp, Jennifer; Yao, Song; Garber, Judy; Cox, Angela; Brauch, Hiltrud; Ambrosone, Christine; Nevanlinna, Heli; Yannoukakos, Drakoulis; Slager, Susan L.; Vachon, Celine M.; Eccles, Diana M.; Fasching, Peter A.

2015-01-01

Purpose Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients and Methods Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Results Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations. Conclusion Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives. PMID:25452441

Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.

PubMed

Schuetz, Philipp; Hausfater, Pierre; Amin, Devendra; Amin, Adina; Haubitz, Sebastian; Faessler, Lukas; Kutz, Alexander; Conca, Antoinette; Reutlinger, Barbara; Canavaggio, Pauline; Sauvin, Gabrielle; Bernard, Maguy; Huber, Andreas; Mueller, Beat

2015-10-29

Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer.

PubMed

Couch, Fergus J; Hart, Steven N; Sharma, Priyanka; Toland, Amanda Ewart; Wang, Xianshu; Miron, Penelope; Olson, Janet E; Godwin, Andrew K; Pankratz, V Shane; Olswold, Curtis; Slettedahl, Seth; Hallberg, Emily; Guidugli, Lucia; Davila, Jaime I; Beckmann, Matthias W; Janni, Wolfgang; Rack, Brigitte; Ekici, Arif B; Slamon, Dennis J; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Fountzilas, George; Pelttari, Liisa M; Tapper, William J; Durcan, Lorraine; Cross, Simon S; Pilarski, Robert; Shapiro, Charles L; Klemp, Jennifer; Yao, Song; Garber, Judy; Cox, Angela; Brauch, Hiltrud; Ambrosone, Christine; Nevanlinna, Heli; Yannoukakos, Drakoulis; Slager, Susan L; Vachon, Celine M; Eccles, Diana M; Fasching, Peter A

2015-02-01

Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations. Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives. © 2014 by American Society of Clinical Oncology.

ALCOHOLIC VERSUS NONALCOHOLIC CIRRHOSIS IN A RANDOMIZED CONTROLLED TRIAL OF EMERGENCY THERAPY OF BLEEDING VARICES

PubMed Central

Orloff, Marshall J.; Isenberg, Jon I.; Wheeler, Henry O.; Haynes, Kevin S.; Jinich-Brook, Horacio; Rapier, Roderick; Vaida, Florin; Hye, Robert J.; Orloff, Susan L.

2010-01-01

Background It has been proposed that portal-systemic shunts be avoided in alcoholic cirrhotics because survival rate is allegedly lower in alcoholics than in nonalcoholics. We examined this issue in a randomized controlled trial. Methods 211 unselected, consecutive patients with cirrhosis and bleeding esophageal varices were randomized to endoscopic sclerotherapy (EST) (n=106) or emergency portacaval shunt (EPCS) (105). Treatment was initiated within 8 hours. EST failure was treated by rescue PCS. 10-yr follow-up was 96%. Results Results strongly favored EPCS over EST (p<0.001). Among EPCS patients, 83% were alcoholic and 17% nonalcoholic. Outcomes were (1) permanent control of bleeding 100% vs. 100%; (2) 5-yr survival 71% vs.78%; (3) encephalopathy 14% vs. 19%; (4) yearly charges $38,300 vs. $43,000. Conclusions EPCS results were similar in alcoholic and nonalcoholic cirrhotics. EPCS is an effective first line emergency treatment in all forms of cirrhosis, including alcoholic. PMID:21195430

Trends in survival of multiple myeloma: a thirty-year population-based study in a single institution.

PubMed

Ríos-Tamayo, Rafael; Sánchez, María José; Puerta, José Manuel; Sáinz, Juan; Chang, Daysi-Yoe-Ling; Rodríguez, Teresa; López, Pilar; de Pablos, José María; Navarro, Pilar; de Veas, José Luís García; Romero, Antonio; Garrido, Pilar; Moratalla, Lucía; Alarcón-Payer, Carolina; López-Fernández, Elisa; González, Pedro Antonio; Jiménez-Moleón, José Juan; Calleja-Hernández, Miguel Ángel; Jurado, Manuel

2015-10-01

Despite the progress made in recent years, multiple myeloma is still considered an incurable disease. Most survival data come from clinical trials. Little is known about the outcome in unselected real-life patients. Overall survival was analyzed in a cohort of newly diagnosed symptomatic multiple myeloma patients, over the last three decades, in a single institution population-based study. 582 consecutive myeloma patients were included in the study. Survival increased over time in patients younger than 65 years but did not reach statistical significance in patients with 65 years or older. The prognostic factors associated with overall survival were the International Staging System, the serum lactate dehydrogenase level, the renal impairment, the realization of autologous stem cell transplantation, and the presence of concomitant amyloidosis. Overall survival shows a steady improvement over time. The survival of myeloma is improving progressively in real-life patients, particularly after the widespread use of the novel agents. A comprehensive assessment of comorbidity can help to explain the huge heterogeneity of myeloma outcome. The optimization of current therapeutic resources as well as the incorporation of new drugs will allow further improvement of survival in the coming years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Utility of the CPS+EG staging system in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with neoadjuvant chemotherapy.

PubMed

Marmé, Frederik; Lederer, Bianca; Blohmer, Jens-Uwe; Costa, Serban Dan; Denkert, Carsten; Eidtmann, Holger; Gerber, Bernd; Hanusch, Claus; Hilfrich, Jörn; Huober, Jens; Jackisch, Christian; Kümmel, Sherko; Loibl, Sibylle; Paepke, Stefan; Untch, Michael; von Minckwitz, Gunter; Schneeweiss, Andreas

2016-01-01

Pathologic complete response after neoadjuvant chemotherapy (NACT) correlates with overall survival (OS) in primary breast cancer. A recently described staging system based on pre-treatment clinical stage (CS), final pathological stage (PS), estrogen receptor (ER) status and nuclear grade (NG) leads to a refined estimation of prognosis in unselected patients. Its performance in luminal type breast cancers has not been determined. This study investigates the clinical utility of this CPS+EG score when restricted to hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) patients and compares the results to a cohort of unselected patients. The CPS+EG score was calculated for 6637 unselected patients and 2454 patients with HR+/HER2- tumours who received anthracycline/taxane-based NACT within 8 prospective German trials. Five-year disease-free survival (DFS) and OS were 75.6% and 84.1% for the unselected cohort and 80.6% and 87.8% for the HR+/HER2- subgroup, respectively. The CPS+EG system distinguished different prognostic groups with 5-year DFS ranging from 0% to 91%. The CPS+EG system leads to an improved categorisation of patients by outcome compared to CS, PS, ER or NG alone. When applying the CPS+EG score to the HR+/HER2- subgroup, a shift to lower scores was observed compared to the overall population, but 5-year DFS and OS for the individual scores were identical to that observed in the overall population. In HR+/HER2- patients, the CPS+EG staging system retains its ability to facilitate a refined stratification of patients according to outcome. It can help to select candidates for post-neoadjuvant clinical trials in luminal breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia

PubMed Central

Wen, Wei Xiong; Allen, Jamie; Lai, Kah Nyin; Mariapun, Shivaani; Hasan, Siti Norhidayu; Ng, Pei Sze; Lee, Daphne Shin-Chi; Lee, Sheau Yee; Yoon, Sook-Yee; Lim, Joanna; Lau, Shao Yan; Decker, Brennan; Pooley, Karen; Dorling, Leila; Luccarini, Craig; Baynes, Caroline; Conroy, Don M; Harrington, Patricia; Simard, Jacques; Yip, Cheng Har; Mohd Taib, Nur Aishah; Ho, Weang Kee; Antoniou, Antonis C; Dunning, Alison M; Easton, Douglas F

2018-01-01

Background Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls. Methods Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing. Results Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing. Conclusion Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia. PMID:28993434

Prognosis and guideline-adherent antithrombotic treatment in patients with atrial fibrillation and atrial flutter: implications of undertreatment and overtreatment in real-life clinical practice; the Loire Valley Atrial Fibrillation Project.

PubMed

Gorin, Laurent; Fauchier, Laurent; Nonin, Emilie; Charbonnier, Bernard; Babuty, Dominique; Lip, Gregory Y H

2011-10-01

In patients with atrial fibrillation (AF), adherence to guidelines for antithrombotic treatment is poorly followed, and undertreatment (or nonadherence with guidelines) is associated with a worse prognosis. The study objective was to evaluate whether this was also the case in a large contemporary series of unselected patients with AF in real-world clinical practice. All patients with AF or atrial flutter seen in our institution between 2000 and 2007 were identified in a database and followed up for mortality and stroke. Antithrombotic guideline adherence was assessed according to the 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines. We reviewed outcomes in 3,646 consecutive patients with AF or atrial flutter (aged 71 ± 14 years; mean CHADS(2) [congestive heart failure, hypertension, aged ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score, 1.5 ± 1.1). Antithrombotic treatment was in agreement with the guidelines in 53% of patients, whereas 31% were classified as undertreated and 16% as overtreated. Among other parameters, nonpermanent AF and atrial flutter were independently associated with an increased risk of undertreatment. After a follow-up of 953 ± 767 days (median, 771 days; interquartile range, 1,286 days), guideline adherence was associated with a lower risk of adverse events (death from all causes or stroke) compared with undertreatment (relative risk, 0.47; 95% CI, 0.40-0.55; P < .0001). Overtreatment was associated with a lower risk of adverse events compared with the guideline-adherent population (relative risk, 0.40; 95% CI, 0.28-0.58; P < .0001). Factors independently associated with increased risk of mortality or stroke were antithrombotic undertreatment, older age, heart failure, renal failure, diabetes, male sex, and previous history of stroke. Guideline nonadherence and undertreatment with antithrombotic agents in unselected real-world patients with AF or atrial flutter are independently associated with a high risk of stroke and mortality.

Opportunistic screening of atrial fibrillation by automatic blood pressure measurement in the community.

PubMed

Omboni, Stefano; Verberk, Willem J

2016-04-12

Timely detection of atrial fibrillation (AF) may effectively prevent cardiovascular consequences. However, traditional diagnostic tools are either poorly reliable (pulse palpation) or not readily accessible (ECG) in general practice. We tested whether an automatic oscillometric blood pressure (BP) monitor embedded with an algorithm for AF detection might be effective for opportunistic screening of asymptomatic AF in the community. A community-based screening campaign in an unselected population to verify the feasibility of AF screening with a Microlife WatchBP Office BP monitor with a patented AFIB algorithm. When possible AF was detected (≥2 of 3 BP measurements reporting AF), a doctor immediately performed a single-lead ECG in order to confirm or exclude the presence of the arrhythmia. The main demographic and clinical data were also collected. 220 consecutive participants from an unselected sample of individuals in a small Italian community. Number of patients detected with AF and diagnosed risk factors for AF. In 12 of 220 participants, the device detected possible AF during the BP measurement: in 4 of them (1.8%), the arrhythmia was confirmed by the ECG. Patients with AF were more likely to be older (77.0±1.2 vs 57.2±15.2 years, p=0.010), obese (50.0 vs 14.4%, p=0.048) and to suffer from a cardiovascular disease (50.0 vs 10.6%, p=0.014) than patients without AF. Participants with a positive BP AF reading and non-AF arrhythmias (n=8) did not differ in their general characteristics from participants with a negative BP AF reading and were younger than patients with AF (mean age 56.4±14.8, p=0.027; 5 of 8 participants aged <65 years). Opportunistic screening of AF by BP measurement is feasible to diagnose this arrhythmia in unaware participants, particularly in those older than 65 years, who are the target patient group recommended by current AF screening guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Usefulness of Electrocardiographic QT Interval to Predict Left Ventricular Diastolic Dysfunction

PubMed Central

Wilcox, Jane E.; Rosenberg, Jonathan; Vallakati, Ajay; Gheorghiade, Mihai; Shah, Sanjiv J.

2013-01-01

Whether a normal electrocardiogram excludes left ventricular (LV) diastolic dysfunction (DD) and whether electrocardiographic parameters are associated with DD is unknown. We therefore sought to investigate the relation between electrocardiographic parameters and DD. We first evaluated 75 consecutive patients referred for echocardiography for clinical suspicion of heart failure (phase 1). Electrocardiography and comprehensive echocardiography were performed on all patients and were analyzed separately in a blinded fashion. Receiver operating characteristic curves and multivariate regression analyses were used to determine which electrocardiographic parameters were most closely associated with DD. Next, we prospectively validated our results in 100 consecutive, unselected patients undergoing echocardiography (phase 2). In phase 1 of our study, the mean age was 59 ± 14 years, 41% were women, 31% had coronary disease, 53% had hypertension, and 25% had diabetes. The mean ejection fraction was 54 ± 15%, and 64% had DD. Of all the electrocardiographic parameters, the QTc interval was most closely associated with DD. QTc was inversely associated with E′ velocity (r = −0.54, p <0.0001), and the area under the receiver operating characteristic curve for QTc as a predictor of DD was 0.82. QTc prolongation was independently associated with reduced E′ velocity (p = 0.021 after adjustment for age, gender, medications, QRS duration, and ejection fraction). In phase 2 of our study QTc was the electrocardiographic parameter most associated with reduced E′ velocity (435 ± 31 vs 419 ± 24 ms; p = 0.004), confirming our phase 1 study findings. In conclusion, QTc prolongation was the electrocardiographic marker most predictive of DD and was independently associated with DD. PMID:21907948

Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia.

PubMed

Wen, Wei Xiong; Allen, Jamie; Lai, Kah Nyin; Mariapun, Shivaani; Hasan, Siti Norhidayu; Ng, Pei Sze; Lee, Daphne Shin-Chi; Lee, Sheau Yee; Yoon, Sook-Yee; Lim, Joanna; Lau, Shao Yan; Decker, Brennan; Pooley, Karen; Dorling, Leila; Luccarini, Craig; Baynes, Caroline; Conroy, Don M; Harrington, Patricia; Simard, Jacques; Yip, Cheng Har; Mohd Taib, Nur Aishah; Ho, Weang Kee; Antoniou, Antonis C; Dunning, Alison M; Easton, Douglas F; Teo, Soo Hwang

2018-02-01

Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls. Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing. Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing. Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2 . While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Kidney and urinary tract polyomavirus infection and distribution: molecular biology investigation of 10 consecutive autopsies.

PubMed

Boldorini, Renzo; Veggiani, Claudia; Barco, Diana; Monga, Guido

2005-01-01

Distinct human polyomavirus genotypes cause different diseases in patients with renal transplants: BK virus (BKV) causes tubulointerstitial nephritis and ureteral stenosis, whereas both JC virus (JCV) and BKV are responsible for hemorrhagic cystitis. These findings could result from a selective infection of kidney and urinary tract segments by JCV or BKV. To verify this hypothesis, 10 complete, unselected, consecutive autopsies from 9 immunocompetent patients and 1 patient affected by acquired immunodeficiency syndrome were investigated. Samples from kidneys (n = 80), renal pelvis (n = 20), ureter (n = 40), and urinary bladder (n = 30) obtained from 10 consecutive autopsies were investigated by means of multiplex nested polymerase chain reaction to detect polyomavirus DNA and to distinguish different species of the Polyomavirus genus. In situ hybridization and immunohistochemistry were also carried out to define the viral status of the infected tissues. Polyomavirus DNA was detected in all of the subjects (positive samples ranging from 2 to 7 samples), for a total of 43 of 170 samples (25.3%), distributed as follows: urinary bladder (10/30, 33%), renal pelvis (6/20, 30%), ureter (10/40, 25%), and kidney tissue (17/80, 21%). We found that JCV was most frequently detected overall (23/43 samples, 53.5%) and was also detected most frequently within the kidney (8/17 positive samples, 47%), the renal pelvis (5/6 positive samples, 70%), and the ureter (7/10 positive samples, 70%), whereas BKV was found in 14 samples (32.5%), and it was the prevailing genotype in urinary bladder (6/10 positive samples, 60%). Coinfection of BKV-JCV was found in 6 samples (14%). Immunohistochemistry and in situ hybridization returned negative results. The viruses JCV and BKV latently persist randomly in kidney and urinary tract. Distinct diseases induced by them could be related more closely to molecular viral rearrangements than to the topographic distribution of latent viruses.

Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study.

PubMed

Duruisseaux, Michaël; Besse, Benjamin; Cadranel, Jacques; Pérol, Maurice; Mennecier, Bertrand; Bigay-Game, Laurence; Descourt, Renaud; Dansin, Eric; Audigier-Valette, Clarisse; Moreau, Lionel; Hureaux, José; Veillon, Remi; Otto, Josiane; Madroszyk-Flandin, Anne; Cortot, Alexis; Guichard, François; Boudou-Rouquette, Pascaline; Langlais, Alexandra; Missy, Pascale; Morin, Franck; Moro-Sibilot, Denis

2017-03-28

Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib.At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months.Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

A new pretest probability score for diagnosis of lower limb deep vein thrombosis in unselected population of outpatients and inpatients.

PubMed

Sermsathanasawadi, Nuttawut; Chaivanit, Trakarn; Suparatchatpun, Pinyo; Chinsakchai, Khamin; Wongwanit, Chumpol; Ruangsetakit, Chanean; Mutirangura, Pramook

2017-03-01

Objective To develop a new pretest probability score for deep vein thrombosis (DVT) in unselected population of outpatients and inpatients. Methods The new score was developed using independent factors from 500 patients clinically suspected of leg DVT. The new score was validated in a second group of 315 patients. Results The score consists of four components: unilateral leg pain, confinement to bed, calf enlargement >3 cm compared with the other side, and previous venous thromboembolism. A score ≥2 indicated a high probability while a score <2 indicated low probability. The sensitivity and specificity of the new score were 71.60% and 79.49%, respectively. The area under the receiver operating characteristic curve for the new score was 0.79. The combination of a new score <2 and D-dimer level <500 µg/L had a negative predictive value of 96.43%. Conclusions Our new score was valid in an unselected population of outpatients and inpatients.

Perceived cognitive function in coronary artery disease--an unrecognised predictor of unemployment.

PubMed

Kiessling, Anna; Henriksson, Peter

2005-08-01

We aimed to assess whether perceived cognitive function influences employment and return to work in patients with coronary artery disease (CAD). Prospective longitudinal cohort study. Health care system of Södertälje, Stockholm County, Sweden. We included consecutive unselected patients less than 65 years of age with CAD and followed them during 2 years. Gainful employment and return to work in patients with CAD. We found that perceived cognitive function predicts both prevalence of unemployment [OR 2.06 (95% CI: 1.36-3.13); p = 0.0006] and early retirement and sick leave due to coronary artery disease [OR 1.59 (95% CI: 1.12-2.25)] both at baseline and 2 years later. Furthermore, perceived cognitive function predicted return to work after an acute coronary event [OR 2.28 (95% CI: 1.08-4.84)]. Covariates such as age, sex, prevalence and degree of angina (CCS grade), cardiovascular risk factors and events did not change the predictive power. Perceived cognitive function is a hitherto unrecognised independent predictor of unemployment, sick leave and return to work in patients with coronary artery disease. Perceived cognitive function adds a new perspective on ability to gainful employment in patients with CAD. The findings might have significance both to individual care and to society.

Psychometric properties of the dimensional anxiety scales for DSM-V in an unselected sample of German treatment seeking patients.

PubMed

Beesdo-Baum, Katja; Klotsche, Jens; Knappe, Susanne; Craske, Michelle G; Lebeau, Richard T; Hoyer, Jürgen; Strobel, Anja; Pieper, Lars; Wittchen, Hans-Ulrich

2012-12-01

Dimensional assessments are planned to be included as supplements to categorical diagnoses in DSM-V. The aim of this study was to examine the unidimensionality, reliability, validity, and clinical sensitivity of brief self-rated scales for specific anxiety disorders in an unselected German sample of consecutive attendees to a psychological clinic. These scales use a common template to assess core constructs of fear and anxiety. Dimensional scales for social anxiety disorder, specific phobia, agoraphobia, panic disorder, and generalized anxiety disorder were administered along with established scales to 102 adults seeking treatment for mental health problems at a German university outpatient clinic for psychotherapy. The computer-assisted clinical version of the Munich-Composite International Diagnostic Interview was used to assess mental disorders according to DSM-IV criteria. Dimensionality and scale reliability were examined using confirmatory factor analyses. Convergent and discriminant validity were examined by testing differences in the size of correlations between each dimensional anxiety scale and each of the previously validated scales. Each dimensional scale's ability to correctly differentiate between individuals with versus without an anxiety diagnosis was examined via the area under the curve. Analyses revealed unidimensionality for each scale, high reliability, and convergent and discriminant validity. Classification performance was good to excellent for all scales except for specific phobia. The application of the dimensional anxiety scales may be an effective way to screen for specific anxiety disorders and to supplement categorical diagnoses in DSM-V, although further evaluation and refinement of the scales (particularly the specific phobia scale) is needed. © 2012 Wiley Periodicals, Inc.

Automated point-of-care testing for ABO agglutination test: proof of concept and validation.

PubMed

El Kenz, H; Corazza, F

2015-07-01

ABO-incompatible red blood cell transfusions still represent an important hazard in transfusion medicine. Therefore, some countries have introduced a systematic bedside ABO agglutination test checking that the right blood is given to the right patient. However, this strategy requires an extremely time-consuming learning programme and relies on a subjective interpretation of ABO test cards agglutination. We developed a prototype of a fully automated device performing the bedside agglutination test that could be completed by reading of a barcoded wristband. This POCT checks the ABO compatibility between the patient and the blood bag. Proof of concept and analytical validation of the prototype has been completed on 451 blood samples: 238 donor packed red blood cells, 137 consecutive unselected patients for whom a blood group determination had been ordered and on 76 patient samples selected with pathology that could possibly interfere with or impair performances of the assay. We observed 100% concordance for ABO blood groups between the POCT and the laboratory instrument. These preliminary results demonstrate the feasibility of ABO determination with a simple POCT device eliminating manipulation and subjective interpretation responsible for transfusion errors. This device should be linked to the blood bank system allowing all cross-check of the results. © 2015 International Society of Blood Transfusion.

Real-world clopidogrel utilization in acute coronary syndromes: patients selection and outcomes in a single-center experience.

PubMed

Castini, Diego; Persampieri, Simone; Cazzaniga, Sara; Ferrante, Giulia; Centola, Marco; Lucreziotti, Stefano; Salerno-Uriarte, Diego; Sponzilli, Carlo; Carugo, Stefano

2017-12-01

With this study, we sought to identify patient characteristics associated with clopidogrel prescription and its relationship with in-hospital adverse events in an unselected cohort of ACSs patients. We studied all consecutive patients admitted at our institution for ACSs from 2012 to 2014. Patients were divided into two groups based on clopidogrel or novel P2Y12 inhibitors (prasugrel or ticagrelor) prescription and the relationship between clopidogrel use and patient clinical characteristics and in-hospital adverse events was evaluated using logistic regression analysis. The population median age was 68 years (57-77 year) and clopidogrel was prescribed in 230 patients (46%). Patients characteristics associated with clopidogrel prescription were older age, female sex, non-ST-elevation ACS diagnosis, the presence of diabetes mellitus and anemia, worse renal and left ventricular functions and a higher Killip class. Patients on clopidogrel demonstrated a significantly higher incidence of in-hospital mortality (4.8%) than prasugrel and ticagrelor-treated patients (0.4%), while a nonstatistically significant trend emerged considering bleeding events. However, on multivariable logistic regression analysis female sex, the presence of anemia and Killip class were the only variables independently associated with in-hospital death. Patients treated with clopidogrel showed a higher in-hospital mortality. However, clinical variables associated with its use identify a population at high risk for adverse events and this seems to play a major role for the higher in-hospital mortality observed in clopidogrel-treated patients.

A perspective on the use of an enhanced recovery program in open, non-instrumented day surgery for degenerative lumbar and cervical spinal conditions.

PubMed

Venkata, Hari K; van Dellen, James R

2018-06-01

A means of significantly shortening patients' length of hospital stay, improving their outcome and thereby also reducing costs is to use an enhanced recovery program (ERP) which is increasingly being used in a number of surgical sub-specialties. This paper provides a perspective on its prospective use in a wide-ranging, unselected cohort of patients undergoing open spinal surgery for degenerative lumbar and cervical spinal conditions. Selected spinal cases undergoing day surgery have been increasingly reported. A prospective, unselected, consecutive cohort of 246 cases, over an 18-month period, undergoing open, non-instrumented decompression spinal surgery and using ERP (and the concept of "bundles of care") was analyzed. Nine cases could not be included as they did not fully meet the entry criteria. No routine follow-up was arranged for the study group. The ages ranged widely, from 23-90 years (mean 57). In 187 the surgery for degenerative conditions was lumbar and in 50 cervical. The ASA (American Association of Anesthesiologists) ratings were 108=1; 107=2 and 22=3. Using the United Kingdom (UK) National Health Service (NHS) definitions of length of stay 225 (95%) could be finally classified as "ambulatory" and 12 (5%) were "short stay". A sub-cohort of 126 (53.2%) were "day cases". The follow-up was >1 year for all. There were no wound infections reported; 5 postdischarge cases (2.1%) needed to be seen in the Accident and Emergency (A&E) Department (less than 4 days postsurgery), but none needed re-admission; and there were 7 re-admissions (2.5%), between 4 and 30 days, and of these 6 required a further surgical procedure. There were no long-term instability complications reported in this cohort. ERP can be used for spinal surgery. There were identifiable and correctable medical and social factors found on analysis which could significantly increase the "day cases" number to over 90%.

Comparison of the feasibility and effectiveness of transradial coronary angiography via right versus left radial artery approaches (from the PREVAIL Study).

PubMed

Pelliccia, Francesco; Trani, Carlo; Biondi-Zoccai, Giuseppe G L; Nazzaro, Marco; Berni, Andrea; Patti, Giuseppe; Patrizi, Roberto; Pironi, Bruno; Mazzarotto, Pietro; Gioffrè, Gaetano; Speciale, Giulio; Pristipino, Christian

2012-09-15

It remains undefined if transradial coronary angiography from a right or left radial arterial approach differs in real-world practice. To address this issue, we performed a subanalysis of the PREVAIL study. The PREVAIL study was a prospective, multicenter, observational survey of unselected consecutive patients undergoing invasive cardiovascular procedures over a 1-month observation period, specifically aimed at assessing the outcomes of radial approach in the contemporary real world. The choice of arterial approach was left to the discretion of the operator. Prespecified end points of this subanalysis were procedural characteristics. Of 1,052 patients consecutively enrolled, 509 patients underwent transradial catheterization, 304 with a right radial and 205 with a left radial approach. Procedural success rates were similar between the 2 groups. Compared to the left radial group, the right radial group had longer procedure duration (46 ± 29 vs 33 ± 24 minutes, p <0.0001) and fluoroscopy time (765 ± 787 vs 533 ± 502, p <0.0001). At multivariate analysis, including a parsimonious propensity score for the choice of left radial approach, duration of procedure (beta coefficient 11.38, p <0.001) and total dose-area product (beta coefficient 11.38, p <0.001) were independently associated with the choice of the left radial artery approach. The operator's proficiency in right/left radial approach did not influence study results. In conclusion, right and left radial approaches are feasible and effective to perform percutaneous procedures. In the contemporary real world, however, the left radial route is associated with shorter procedures and lower radiologic exposure than the right radial approach, independently of an operator's proficiency. Copyright © 2012 Elsevier Inc. All rights reserved.

Determinants of quality of life in stroke survivors and their informal caregivers.

PubMed

Jönsson, Ann-Cathrin; Lindgren, Ingrid; Hallström, Björn; Norrving, Bo; Lindgren, Arne

2005-04-01

We examined longitudinal changes of quality of life (QOL) covering physical and mental factors in an unselected group of stroke patients and their informal caregivers. Our hypothesis was that informal caregivers would have better QOL than patients at both follow-ups, and that changes, if any, would be related to the patients' status. QOL of 304 consecutive stroke patients and their 234 informal caregivers from the population-based Lund Stroke Register was assessed 4 months after stroke onset with the Short Form 36 (SF-36) questionnaire. SF-36 was repeated for both groups after 16 months together with Mini Mental State Examination (MMSE) and Geriatric Depression Scale (GDS-20) for patients. The patients' mean QOL scores improved between 4 and 16 months after stroke in the socio-emotional and mental SF-36 domains and decreased in the domain physical function. Multivariate analyses showed that the patients' most important determinants of QOL after 16 months were GDS-20 score, functional status, age, and gender. Informal caregivers had better QOL than patients except for the domain role emotional and the mental component summary. The caregivers' most important determinants of QOL were their own age and the patients' functional status. Our study highlights depressive symptoms in determining QOL of stroke patients. Despite self-perceived deterioration in physical function over time, several other components of QOL improved, suggesting internal adaptation to changes in their life situations. Informal caregivers of stroke patients may be under considerable strain as suggested by their lower emotional-mental scores.

Prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer.

PubMed

Kast, Karin; Dobberschütz, Catharina; Sadowski, Carolin Eva; Pistorius, Steffen; Wimberger, Pauline

2016-11-01

Lynch syndrome is known by healthcare providers mainly for patients with colorectal cancer. Awareness of other associated tumors, such as endometrial or ovarian cancer, is low. This study aimed to analyze the prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer. In addition, the willingness of patients and family members to undergo germline mutation testing was investigated. The medical records of all patients diagnosed with endometrial or ovarian cancer at the Department of Gynecology and Obsterics, University Hospital Dresden, between 1998 and 2012, were screened for a family history of HNPCC-associated cancer. Telephone interviews were used to screen, inform, and enroll patients in this genetic analysis study. Molecular analysis was performed by prescreening of tumor tissue, followed by germline mutation analysis. Two hundred and eighty-three patients were diagnosed with endometrial cancer, 291 with ovarian cancer, and 14 with both. A positive family history for tumors associated with Lynch syndrome was documented for 61 patients. Two pathogenic mutations in the genes MLH1 and MSH2 in nine genetic analyses had already been detected before. After genetic counseling, only 10 of 31 index patients (32.3 %) consented for mutation analysis. However, no additional pathogenic heterozygous mutations were found. In this retrospective cohort study in unselected patients with endometrial or ovarian cancer, only a small number of patients with suspected Lynch syndrome could be identified. Of those, acceptance of germline analyses was moderate, only. As a result, the rate of identified pathogenic germline mutations was lower than expected. Therefore, we are convinced that more information on cancer risks, options for predictive molecular testing and preventive procedures, needs to be provided to patients and gynecologists.

Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis

PubMed Central

Langlois, Vincent; Lesourd, Anais; Girszyn, Nicolas; Ménard, Jean-Francois; Levesque, Hervé; Caron, Francois; Marie, Isabelle

2016-01-01

Abstract To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with infective endocarditis (IE) in internal medicine; and to compare clinical and biochemical features and outcome between patients exhibiting IE with and without ANCA. Fifty consecutive patients with IE underwent ANCA testing. The medical records of these patients were reviewed. Of the 50 patients with IE, 12 exhibited ANCA (24%). ANCA-positive patients with IE exhibited: longer duration between the onset of first symptoms and IE diagnosis (P = 0.02); and more frequently: weight loss (P = 0.017) and renal impairment (P = 0.08), lower levels of C-reactive protein (P = 0.0009) and serum albumin (P = 0.0032), involvement of both aortic and mitral valves (P = 0.009), and longer hospital stay (P = 0.016). Under multivariate analysis, significant factors for ANCA-associated IE were: longer hospital stay (P = 0.004), lower level of serum albumin (P = 0.02), and multiple valve involvement (P = 0.04). Mortality rate was 25% in ANCA patients; death was because of IE complications in all these patients. Our study identifies a high prevalence of ANCA in unselected patients with IE in internal medicine (24%). Our findings further underscore that ANCA may be associated with a subacute form of IE leading to multiple valve involvement and more frequent renal impairment. Because death was due to IE complications in all patients, our data suggest that aggressive therapy may be required to improve such patients’ outcome. PMID:26817911

Lentiviral-mediated genetic correction of hematopoietic and mesenchymal progenitor cells from Fanconi anemia patients.

PubMed

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Lozano, M Luz; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-06-01

Previous clinical trials based on the genetic correction of purified CD34(+) cells with gamma-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34(+) cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34(+) cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34(-) mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs).

Lentiviral-mediated Genetic Correction of Hematopoietic and Mesenchymal Progenitor Cells From Fanconi Anemia Patients

PubMed Central

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Luz Lozano, M; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-01-01

Previous clinical trials based on the genetic correction of purified CD34+ cells with γ-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34+ cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34+ cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34− mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs). PMID:19277017

Strengths and weaknesses of 'real-world' studies involving non-vitamin K antagonist oral anticoagulants.

PubMed

Camm, A John; Fox, Keith A A

2018-01-01

Randomised controlled trials (RCTs) provide the reference standard for comparing the efficacy of one therapy or intervention with another. However, RCTs have restrictive inclusion and exclusion criteria; thus, they are not fully representative of an unselected real-world population. Real-world evidence (RWE) studies encompass a wide range of research methodologies and data sources and can be broadly categorised as non-interventional studies, patient registries, claims database studies, patient surveys and electronic health record studies. If appropriately designed, RWE studies include a patient population that is far more representative of unselected patient populations than those of RCTs, but they do not provide a robust basis for comparing treatment strategies. RWE studies can have very large sample sizes, can provide information on treatments in patient groups that are usually excluded from RCTs, are generally less expensive and quicker than RCTs, and can assess a broad range of outcomes. Limitations of RWE studies can include low internal validity, lack of quality control surrounding data collection and susceptibility to multiple sources of bias for comparing outcomes. RWE studies can complement the findings from RCTs by providing valuable information on treatment practices and patient characteristics among unselected patients. This information is necessary to guide treatment decisions and for reimbursement and payment decisions. RWE studies have been extensively applied in the postmarketing approval assessment of non-vitamin K antagonist oral anticoagulants since 2010. However, the benefits, costs, limitations and methodological challenges associated with the different types of RWE must be considered carefully when interpreting the findings.

Strengths and weaknesses of ‘real-world’ studies involving non-vitamin K antagonist oral anticoagulants

PubMed Central

Camm, A John; Fox, Keith A A

2018-01-01

Randomised controlled trials (RCTs) provide the reference standard for comparing the efficacy of one therapy or intervention with another. However, RCTs have restrictive inclusion and exclusion criteria; thus, they are not fully representative of an unselected real-world population. Real-world evidence (RWE) studies encompass a wide range of research methodologies and data sources and can be broadly categorised as non-interventional studies, patient registries, claims database studies, patient surveys and electronic health record studies. If appropriately designed, RWE studies include a patient population that is far more representative of unselected patient populations than those of RCTs, but they do not provide a robust basis for comparing treatment strategies. RWE studies can have very large sample sizes, can provide information on treatments in patient groups that are usually excluded from RCTs, are generally less expensive and quicker than RCTs, and can assess a broad range of outcomes. Limitations of RWE studies can include low internal validity, lack of quality control surrounding data collection and susceptibility to multiple sources of bias for comparing outcomes. RWE studies can complement the findings from RCTs by providing valuable information on treatment practices and patient characteristics among unselected patients. This information is necessary to guide treatment decisions and for reimbursement and payment decisions. RWE studies have been extensively applied in the postmarketing approval assessment of non-vitamin K antagonist oral anticoagulants since 2010. However, the benefits, costs, limitations and methodological challenges associated with the different types of RWE must be considered carefully when interpreting the findings. PMID:29713485

Body dysmorphic concerns, social adaptation, and motivation for psychotherapeutic support in dermatological outpatients.

PubMed

Ritter, Viktoria; Fluhr, Joachim W; Schliemann-Willers, Sibylle; Elsner, Peter; Strauß, Bernhard; Stangier, Ulrich

2016-09-01

Dermatologists are increasingly confronted with patients affected by body dysmorphic disorder (BDD). BDD is characterized by excessive preoccupation with one or more perceived defect(s) or flaw(s) in physical appearance which are not observable or appear slight to others. So far, there have been only few studies examining the prevalence of BDD in dermatological outpatients. In addition, the need for psychotherapeutic support in dermatological outpatients with body dysmorphic concerns has not yet been systematically examined. The objective of the present study was therefore to investigate the frequency of body dysmorphic concerns as well as social adaptation and the need for psychotherapeutic support in the aforementioned patient group. A total of 252 dermatological outpatients seen at a German university hospital were consecutively enrolled, and examined using the Dysmorphic Concerns Questionnaire, the Social Adaptation Self-Evaluation Scale, and the German version of the University of Rhode Island Change Assessment Scale. 7.9 % of all outpatients (unselected sample) showed positive test results, suggesting clinically relevant body dysmorphic concerns. Patients with clinically relevant body dysmorphic concerns exhibited poor social adaptation. Contrary to expectations, these patients revealed a high motivation for change, indicating the necessity for psychotherapeutic support. Our findings confirm previous prevalence rates of BDD in dermatological outpatients, and highlight the need for providing psychotherapeutic support to dermatological patients. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Systematic follow-up after curative surgery for colorectal cancer in Norway: a population-based audit of effectiveness, costs, and compliance.

PubMed

Körner, Hartwig; Söreide, Kjetil; Stokkeland, Pål J; Söreide, Jon Arne

2005-03-01

In this study, we analyzed the Norwegian guidelines for systematic follow-up after curative colorectal cancer surgery in a large single institution. Three hundred fourteen consecutive unselected patients undergoing curative surgery for colorectal cancer between 1996 and 1999 were studied with regard to asymptomatic curable recurrence, compliance with the program, and cost. Follow-up included carcinoembryonic antigen (CEA) interval measurements, colonoscopy, ultrasonography of the liver, and radiography of the chest. In 194 (62%) of the patients, follow-up was conducted according to the Norwegian guidelines. Twenty-one patients (11%) were operated on for curable recurrence, and 18 patients (9%) were disease free after curative surgery for recurrence at evaluation. Four metachronous tumors (2%) were found. CEA interval measurement had to be made most frequently (534 tests needed) to detect one asymptomatic curable recurrence. Follow-up program did not influence cancer-specific survival. Overall compliance with the surveillance program was 66%, being lowest for colonoscopy (55%) and highest for ultrasonography of the liver (85%). The total program cost was 228,117 euro (US 280,994 dollars), translating into 20,530 euro (US 25,289 dollars) for one surviving patient after surgery for recurrence. The total diagnosis yield with regard to disease-free survival after surgery for recurrence was 9%. Compliance was moderate. Whether the continuing implementation of such program and cost are justified should be debated.

Progression of abnormal MIB-1 staining patterns of reserve cells in cervical smears from women ultimately developing high grade squamous intraepithelial lesions.

PubMed

Siemens, Frederike C; van Haaften, Carolien; Kuijpers, Johan C; Helmerhorst, Theo J M; Boon, Mathilde E

2006-01-01

To assess, in a longitudinal study in women diagnosed with high grade squamous epithelial lesion (HSIL), the progression over time of proliferative activity in reserve cells using population screening cervical cytology specimens. Twenty consecutive, unselected patients with HSIL lesions were part of the national cervical screening program. From the archives, for each patient, the last prior normal population screening smear was included in the study. Concurrent sets of cervical smears from 80 age-matched women without pathology formed the controls. The original slides were stained using MIB-1 monoclonal antibody. The fraction of MIB-1-positive reserve cells was assessed using systematic random sampling and running progressive means assessment to ensure a sufficient sample size. The proliferation fraction in reserve cells of HSIL patients was significantly raised (mean, 65.0%; range, 53.5-94.1%; p < 0.01) as compared with that in concurrent controls (mean, 12.8%; range, 1.9-45.4%). Prior smears from HSIL patients, although without morphologic abnormalities, had abnormally high proliferation fractions (mean, 59.1%; range, 1.0-94.7%), significantly raised over those from concurrent controls (mean, 9.4%; range In population-based cervical smear screening, HSIL patients already have abnormally raised proliferation fractions of reserve cells, even without morphologic changes in squamous cells, 1-5 (mean, 3.6) years prior to diagnosis.

Neglecting the Left Side of a City Square but Not the Left Side of Its Clock: Prevalence and Characteristics of Representational Neglect

PubMed Central

Guariglia, Cecilia; Palermo, Liana; Piccardi, Laura; Iaria, Giuseppe; Incoccia, Chiara

2013-01-01

Representational neglect, which is characterized by the failure to report left-sided details of a mental image from memory, can occur after a right hemisphere lesion. In this study, we set out to verify the hypothesis that two distinct forms of representational neglect exist, one involving object representation and the other environmental representation. As representational neglect is considered rare, we also evaluated the prevalence and frequency of its association with perceptual neglect. We submitted a group of 96 unselected, consecutive, chronic, right brain-damaged patients to an extensive neuropsychological evaluation that included two representational neglect tests: the Familiar Square Description Test and the O'Clock Test. Representational neglect, as well as perceptual neglect, was present in about one-third of the sample. Most patients neglected the left side of imagined familiar squares but not the left side of imagined clocks. The present data show that representational neglect is not a rare disorder and also support the hypothesis that two different types of mental representations (i.e. topological and non-topological images) may be selectively damaged in representational neglect. PMID:23874416

Recovery after uncomplicated laparoscopic cholecystectomy.

PubMed

Bisgaard, Thue; Klarskov, Birthe; Kehlet, Henrik; Rosenberg, Jacob

2002-11-01

After laparoscopic cholecystectomy, the duration of convalescence is 2 to 3 weeks with an unclear pathogenesis. This study was undertaken to analyze postoperative recovery after uncomplicated elective laparoscopic cholecystectomy. Twenty-four consecutive unselected employed patients were followed up prospectively from 1 week before to 1 week after outpatient laparoscopic cholecystectomy. Daily computerized monitoring of physical motor activity and sleep duration and night sleep fragmentation (actigraphy), subjective sleep quality, pulmonary function, pain, and fatigue were registered. Treadmill exercise performance (preoperatively and at postoperative days 2 and 8) and nocturnal pulse oximetry at the patients' homes (preoperatively and postoperative nights 1-3) were completed. Median age was 41 years (range, 21-56). Compared with preoperatively, levels of physical motor activity, fatigue, and pain scores were normalized 2 days after operation. Subjective sleep quality was significantly worsened on the first postoperative night, and sleep duration was significantly increased on the first 2 postoperative nights. There were no significant perioperative changes in actigraphy night sleep fragmentation, incidence of self-reported awakenings or nightmares/distressing dreams, exercise performance, or nocturnal oxygenation. Pulmonary peak flow measurements were normalized the day after operation. After uncomplicated outpatient laparoscopic cholecystectomy, there is no pathophysiologic basis for recommending a postoperative convalescence of more than 2 to 3 days in otherwise healthy younger patients.

Clinical impact of defibrillation testing at the time of implantable cardioverter-defibrillator insertion.

PubMed

Hadid, Claudio; Atienza, Felipe; Strasberg, Boris; Arenal, Ángel; Codner, Pablo; González-Torrecilla, Esteban; Datino, Tomás; Percal, Tamara; Almendral, Jesús; Ortiz, Mercedes; Martins, Raphael; Martinez-Alzamora, Nieves; Fernandez Aviles, Francisco

2015-01-01

Ventricular fibrillation is routinely induced during implantable cardioverter-defibrillator insertion to assess defibrillator performance, but this strategy is experiencing a progressive decline. We aimed to assess the efficacy of defibrillator therapies and long-term outcome in a cohort of patients that underwent defibrillator implantation with and without defibrillation testing. Retrospective observational series of consecutive patients undergoing initial defibrillator insertion or generator replacement. We registered spontaneous ventricular arrhythmias incidence and therapy efficacy, and mortality. A total of 545 patients underwent defibrillator implantation (111 with and 434 without defibrillation testing). After 19 (range 9-31) months of follow-up, the death rate per observation year (4% vs. 4%; p = 0.91) and the rate of patients with defibrillator-treated ventricular arrhythmic events per observation year (with test: 10% vs. without test: 12%; p = 0.46) were similar. The generalized estimating equations-adjusted first shock probability of success in patients with test (95%; CI 88-100%) vs. without test (98%; CI 96-100%; p = 0.42) and the proportion of successful antitachycardia therapies (with test: 87% vs. without test: 80%; p = 0.35) were similar between groups. There was no difference in the annualized rate of failed first shock per patient and per shocked patient between groups (5% vs. 4%; p = 0.94). In this observational study, that included an unselected population of patients with a defibrillator, no difference was found in overall mortality, first shock efficacy and rate of failed shocks regardless of whether defibrillation testing was performed or not.

Medically unexplained conditions considered by patients in general practice.

PubMed

Tschudi-Madsen, Hedda; Kjeldsberg, Mona; Natvig, Bård; Ihlebaek, Camilla; Straand, Jørund; Bruusgaard, Dag

2014-04-01

Patients frequently present with multiple and 'unexplained' symptoms, often resulting in complex consultations. To better understand these patients is a challenge to health care professionals, in general, and GPs, in particular. In our research on symptom reporting, we wanted to explore whether patients consider that they may suffer from conditions commonly regarded as unexplained, and we explored associations between these concerns and symptom load, life stressors and socio-demographic factors. Consecutive, unselected patients in general practice completed questionnaires addressing eight conditions commonly regarded as unexplained (amalgam poisoning, Candida syndrome, fibromyalgia, food intolerance, electromagnetic hypersensitivity, burnout syndrome, chronic fatigue syndrome and irritable bowel syndrome). With logistic regression, we analysed associations with symptom load, burden of life stressors with negative impact on present health and socio-demographic variables. Out of the 909 respondents (response rate = 88.8%), 863 had complete data. In total, 39.6% of patients had considered that they may suffer from one or more unexplained conditions (UCs). These concerns were strongly and positively associated with recent symptom load and number of life stressors. If we excluded burnout and food intolerance, corresponding associations were found. Patients frequently considered that they may suffer from UCs. The likelihood of such concerns strongly increased with an increasing symptom load and with the number of life stressors with negative impact on present health. Hence, the number of symptoms may be a strong indicator of whether patients consider their symptoms part of such often controversial multisymptom conditions.

Characteristics and care pathways of advanced cancer patients in a palliative-supportive care unit and an oncological ward.

PubMed

Mercadante, Sebastiano; Marchetti, Paolo; Adile, Claudio; Caruselli, Amanda; Ferrera, Patrizia; Costanzi, Andrea; Casuccio, Alessandra

2018-06-01

A supportive palliative care unit (SPCU) may have a positive impact on patients' care. The aim of this study was to compare the pattern of patients admitted to a specialized SPCU and to a traditional oncologic ward (OW) in a consecutive sample of advanced cancer patients. Data on patients demographics, reasons for and kind of admission, care-giver, anticancer treatments, being on/off treatment or uncertain, origin setting, who proposed hospital admission, the use of opioids, and hospitalization were gathered. The same parameters were recorded at discharge. A follow-up was performed by phone 1 month after discharge. Two-hundred patients were surveyed. Awareness of disease was more complete in OW patients (P = 0.001). Uncontrolled pain and symptoms were the prevalent reasons for admission to SPCU (P < 0.0005). Toxicity from chemotherapy was more frequently reported by OW patients (P = 0.001). SPCU patients received higher doses of opioids (P = 0.004). More SPCU patients were referred from home and were discharged home (P < 0.0005 and P = 0.018, respectively). Emergency admissions were more frequently reported in OW patients (P < 0.0005). One month after, more SPCU patients were at home and were still on active treatment (P = 0.002, and P = 0.05, respectively). More OW patients died within 1 month (P = 0.001). SPCU allows a better planning admission to hospital and a better care trajectory in advanced cancer patients in comparison to a busy OW, where unselected emergencies more frequently occur.

Clinical and financial burden of active lupus in Greece: a nationwide study.

PubMed

Bertsias, G; Karampli, E; Sidiropoulos, P; Gergianaki, I; Drosos, A; Sakkas, L; Garyfallos, A; Tzioufas, A; Vassilopoulos, D; Tsalapaki, C; Sfikakis, P; Panopoulos, S; Athanasakis, K; Perna, A; Psomali, D; Kyriopoulos, J; Boumpas, D

2016-10-01

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need. © The Author(s) 2016.

Alcohol septal ablation in obstructive hypertrophic cardiomyopathy: four years of experience at a reference center.

PubMed

Fiarresga, António; Cacela, Duarte; Galrinho, Ana; Ramos, Ruben; de Sousa, Lídia; Bernardes, Luís; Patrício, Lino; Cruz Ferreira, Rui

2014-01-01

We describe our center's initial experience with alcohol septal ablation (ASA) for the treatment of obstructive hypertrophic cardiomyopathy. The procedure, its indications, results and clinical outcomes will be addressed, as will its current position compared to surgical myectomy. To assess the results of ASA in all patients treated in the first four years of activity at our center. We retrospectively studied all consecutive and unselected patients treated by ASA between January 2009 and February 2013. In the first four years of experience 40 patients were treated in our center. In three patients (7.5%) the intervention was repeated. Procedural success was 84%. Minor complications occurred in 7.5%. Two patients received a permanent pacemaker for atrioventricular block (6% of those without previous pacemaker). The major complication rate was 5%. There were no in-hospital deaths; during clinical follow-up (22 ± 14 months) cardiovascular mortality was 2.5% and overall mortality was 5%. The results presented reflect the initial experience of our center with ASA. The success rate was high and in line with published results, but with room to improve with better patient selection. ASA was shown to be safe, with a low complication rate and no procedure-related mortality. Our experience confirms ASA as a percutaneous alternative to myectomy for the treatment of symptomatic patients with obstructive hypertrophic cardiomyopathy refractory to medical treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

PubMed

Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

2015-11-01

On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation

PubMed Central

2012-01-01

Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning. PMID:22770365

Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation.

PubMed

Voga, Gorazd

2012-07-06

Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning.

Critical Dysphagia is Common in Parkinson Disease and Occurs Even in Early Stages: A Prospective Cohort Study.

PubMed

Pflug, Christina; Bihler, Moritz; Emich, Katharina; Niessen, Almut; Nienstedt, Julie Cläre; Flügel, Till; Koseki, Jana-Christiane; Plaetke, Rosemarie; Hidding, Ute; Gerloff, Christian; Buhmann, Carsten

2018-02-01

To assess the prevalence of dysphagia and its typical findings in unselected "real-world" Parkinson patients using an objective gold-standard method. This was a prospective, controlled, cross-sectional study conducted in 119 consecutive Parkinson patients of all stages independent of subjective dysphagia. Patients and 32 controls were clinically and endoscopically examined by flexible endoscopic evaluation of swallowing (FEES) to evaluate the deglutition with regard to three consistencies (water, biscuit, and bread). Typical findings of dysphagia like penetration and aspiration, residues, and leakage were assessed. Dysphagia was common in Parkinson patients and occurred in all, even early, disease stages. Only 5% (6/119) of patients showed a completely unremarkable deglutition. Aspiration was seen in 25% (30/119) of patients and always related to water. Residues occurred in 93% (111/119), most commonly for bread. Leakage was much less frequent and was found in only 3-18%, depending on consistency. In a significant fraction of patients, objective dysphagia was not subjectively perceived. A total of 16% of asymptomatic patients suffered from critical aspiration. Significant swallowing deficiencies already occurred in early disease. Aspiration was found in 4 of 20 (20%) patients with disease duration of less than 2 years. Seven of 57 patients (12%) with Hoehn and Yahr stage 2 suffered from severe aspiration. Given the high frequency of critical aspiration in Parkinson disease, these patients should be evaluated early for dysphagia to avoid complications and recommend an adequate therapy. FEES is a simple, cost efficient, minimally invasive method that is ideally suited for this purpose.

Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II).

PubMed

Westra, Jelmer; Tu, Shengxian; Winther, Simon; Nissen, Louise; Vestergaard, Mai-Britt; Andersen, Birgitte Krogsgaard; Holck, Emil Nielsen; Fox Maule, Camilla; Johansen, Jane Kirk; Andreasen, Lene Nyhus; Simonsen, Jo Krogsgaard; Zhang, Yimin; Kristensen, Steen Dalby; Maeng, Michael; Kaltoft, Anne; Terkelsen, Christian Juhl; Krusell, Lars Romer; Jakobsen, Lars; Reiber, Johan H C; Lassen, Jens Flensted; Bøttcher, Morten; Bøtker, Hans Erik; Christiansen, Evald Høj; Holm, Niels Ramsing

2018-03-01

Quantitative flow ratio (QFR) is a novel diagnostic modality for functional testing of coronary artery stenosis without the use of pressure wires and induction of hyperemia. QFR is based on computation of standard invasive coronary angiographic imaging. The purpose of WIFI II (Wire-Free Functional Imaging II) was to evaluate the feasibility and diagnostic performance of QFR in unselected consecutive patients. WIFI II was a predefined substudy to the Dan-NICAD study (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease), referring 362 consecutive patients with suspected coronary artery disease on coronary computed tomographic angiography for diagnostic invasive coronary angiography. Fractional flow reserve (FFR) was measured in all segments with 30% to 90% diameter stenosis. Blinded observers calculated QFR (Medis Medical Imaging bv, The Netherlands) for comparison with FFR. FFR was measured in 292 lesions from 191 patients. Ten (5%) and 9 patients (5%) were excluded because of FFR and angiographic core laboratory criteria, respectively. QFR was successfully computed in 240 out of 255 lesions (94%) with a mean diameter stenosis of 50±12%. Mean difference between FFR and QFR was 0.01±0.08. QFR correctly classified 83% of the lesions using FFR with cutoff at 0.80 as reference standard. The area under the receiver operating characteristic curve was 0.86 (95% confidence interval, 0.81-0.91) with a sensitivity, specificity, negative predictive value, and positive predictive value of 77%, 86%, 75%, and 87%, respectively. A QFR-FFR hybrid approach based on the present results enables wire-free and adenosine-free procedures in 68% of cases. Functional lesion evaluation by QFR assessment showed good agreement and diagnostic accuracy compared with FFR. Studies comparing clinical outcome after QFR- and FFR-based diagnostic strategies are required. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717. © 2018 The Authors.

Enhanced care for primary hip arthroplasty: factors affecting length of hospital stay.

PubMed

Panteli, Michalis; Habeeb, Shayma'u; McRoberts, John; Porteous, Matthew J

2014-04-01

Enhanced care in joint replacement requires identification and correction of the causes of delay in discharge while ensuring practice remains safe. We conducted prospective studies of factors delaying discharge following hip replacement in 2006 and 2010. Daily data were twice collected prospectively in 100 consecutive unselected primary cemented THR, by an independent observer. Reasons for delays in discharge and variation from the patient pathway were identified and addressed. The mean length of stay (LOS) in 2006 was 4.3 days and in 2010, 3.56 days (target for discharge 4 days). In 2006, 31 patients had a stay of more than 4 days, 17 due to inadequate physiotherapy provision, 10 for medical and 4 for other reasons. In 2010, 15 patients had a stay of more than 4 days, 1 patient had inadequate physiotherapy provision, in 7 cases discharge was delayed because of need for blood transfusion and 7 because of need for catheterisation. Women aged more than 70 with preoperative haemoglobin of <12 g/dL were at particularly high risk of requiring transfusion. Catheterisation was also identified as a factor causing significant increase in LOS. Patients going home in less than 4 days were more likely to have had their operation in the morning. Patient LOS is multifactorial and can be reduced by regular review of the care pathway to effect incremental changes that have a significant impact on reducing stay.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

2014-07-01

The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

Pacemaker diagnostics in atrial fibrillation: limited usefulness for therapy initiation in a pacemaker practice.

PubMed

Yedlapati, Neeraja; Fisher, John D

2014-09-01

We aimed to determine the practical value of pacemaker diagnostics for atrial fibrillation (AF) in an unselected general pacemaker practice, specifically workflow and initiation of anticoagulation or antiarrhythmic drug (AAD) therapy. We prospectively followed consecutive pacemaker interrogations over a period of 1 year to identify patients with AF (burden from 1% to 99%). We contacted referring physicians with AF details, and then determined whether the information resulted in therapeutic changes. Of the 1,100 pacemakers interrogated, 728 were dual chamber (DDDs) with AF diagnostic capability. AF was recorded in 73 (10%) but seven had limited information, leaving 66 patients; of these, 42 (63%) patients were already anticoagulated and in five (7%) patients, anticoagulation had been stopped because of complications. Initial diagnosis of AF was made by the pacemaker in 17 patients (26% of 66; 2% of 728); four (6% of 66) patients were newly initiated on anticoagulation. Of the 66 patients, 17 patients were already on AADs; 49 (74%) had satisfactory rate control or had other issues; only two (3% of 66; 0.3% of 728) received new AADs. Of 728 patients with DDD pacemakers, only 17 were newly discovered to have AF, and six (0.8%) had changes in medications based on the pacemaker data. Adding pacemaker-derived data to existing clinical information had little therapeutic impact, due to a combination of cumbersome workflow, and because AF was usually known to practitioners. Developments in automated monitoring systems may provide more accessible and therapeutically useful information. ©2014 Wiley Periodicals, Inc.

Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing

PubMed Central

Klemp, Jennifer R.; Kimler, Bruce F.; Mahnken, Jonathan D.; Geier, Larry J.; Khan, Qamar J.; Elia, Manana; Connor, Carol S.; McGinness, Marilee K.; Mammen, Joshua M. W.; Wagner, Jamie L.; Ward, Claire; Ranallo, Lori; Knight, Catherine J.; Stecklein, Shane R.; Jensen, Roy A.; Fabian, Carol J.; Godwin, Andrew K.

2014-01-01

NCCN guidelines recommend genetic testing for all triple-negative breast cancer (TNBC) patients aged ≤60 years. However, due to the lack of prospective information in unselected patients, these guidelines are not uniformly adopted by clinicians and insurance carriers. The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population. Stage I–IV TNBC patients were enrolled on a prospective registry at academic and community practices. All patients underwent BRCA1/2 testing. Significant family history (SFH) was defined >1 relative with breast cancer at age ≤50 or ≥1 relative with ovarian cancer. Mutation prevalence in the entire cohort and subgroups was calculated. 207 TNBC patients were enrolled between 2011 and 2013. Racial/ethnic distribution: Caucasian (80 %), African–American (14 %), Ashkenazi (1 %). Deleterious BRCA1/2 mutations were identified in 15.4 % (32/207) of patients (BRCA1:11.1 %, BRCA2:4.3 %). SFH reported by 36 % of patients. Mutation prevalence in patients with and without SFH was 31.6 and 6.1 %, respectively. When assessed by age at TNBC diagnosis, the mutation prevalences were 27.6 % (≤50 years), 11.4 % (51–60 years), and 4.9 % (≥61 years). Using SFH or age ≤50 as criteria, 25 and 34 % of mutations, respectively, were missed. Mutation prevalence in patients meeting NCCN guidelines was 18.3 % (32/175) and 0 % (0/32) in patients who did not meet guidelines (p = .0059). In this unselected academic and community population with negligible Ashkenazi representation, we observed an overall BRCA mutation prevalence rate of 15.4 %. BRCA testing based on NCCN guidelines identified all carriers supporting its routine application in clinical practice for TNBC. PMID:24807107

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study

PubMed Central

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, Sarah; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy; Jimenez-Linan, Mercedes; Sagoo, Gurdeep S; Abbs, Stephen; Hulbert-Williams, Nicholas; Pharoah, Paul; Crawford, Robin; Brenton, James D; Tischkowitz, Marc

2016-01-01

Background Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. Objective To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Methods Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. Results 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. Conclusions The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice. PMID:27208206

Variability of Sorafenib Toxicity and Exposure over Time: A Pharmacokinetic/Pharmacodynamic Analysis

PubMed Central

Ropert, Stanislas; Mir, Olivier; Coriat, Romain; Billemont, Bertrand; Tod, Michel; Cabanes, Laure; Franck, Nathalie; Blanchet, Benoit; Goldwasser, François

2012-01-01

Background. Sorafenib displays major interpatient pharmacokinetic variability. It is unknown whether the pharmacokinetics of sorafenib influence its toxicity. Methods. We analyzed the severity and kinetics of sorafenib-induced toxicities in unselected consecutive patients with cancer, as well as their relationship with biological, clinical, and pharmacokinetic parameters. Toxicity was recorded bimonthly. Sorafenib plasma concentrations were assessed by liquid chromatography. Results. For 83 patients (median age, 62 years; range, 21–84 years), median sorafenib 12-hour area under the curve (AUC0–12) was 52.8 mg · h/L (range: 11.8–199.6). A total of 51 patients (61%) experienced grade 3–4 toxicities, including hand-foot skin reactions (23%), asthenia (18%), and diarrhea (11%). Sorafenib AUC0–12 preceding grade 3–4 toxicities was significantly higher than that observed in the remaining population (61.9 mg · h/L vs. 53 mg · h/L). In 25 patients treated with fixed doses of sorafenib for the first 4 months, median dose-normalized AUC0–12 on day 120 was significantly lower than on day 15 (63 vs. 102 mg · h/L). The incidence of hypertension and hand-foot skin reactions significantly decreased over time. Conclusion. Sorafenib AUC0–12 decreases over time, similarly to the incidence of hypertension and hand-foot skin reactions. Monitoring of sorafenib plasma concentrations may help to prevent acute severe toxicities and detect patients with suboptimal exposure at disease progression. PMID:22752067

Challenging the wisdom of puncture at the calyceal fornix in percutaneous nephrolithotripsy: feasibility and safety study with 137 patients operated via a non-calyceal percutaneous track.

PubMed

Kyriazis, Iason; Kallidonis, Panagiotis; Vasilas, Marinos; Panagopoulos, Vasilios; Kamal, Wissam; Liatsikos, Evangelos

2017-05-01

To present our experience with a central, non-calyceal puncture protocol for percutaneous nephrolithotripsy (PCNL) in an attempt to challenge the opinion of worldwide adopted calyceal puncture as the less traumatic site of percutaneous entrance into the collecting system. During 2012, a total of 137 consecutive, unselected patients were subjected to PCNL in our department. Non-calyceal punctures were performed to all cases and followed by subsequent track dilations up to 30 Fr. Perioperative and postoperative data were prospectively collected and analyzed. Mean operative time (from skin puncture to nephrostomy tube placement) was 48 min. Patients with single, multiple and staghorn stones had primary stone-free rates of 89.2, 80.4 and 66.7 % after PCNL, respectively. The overall complication rate was 10.2 %, while bleeding complications were minimal. Only 4 patients (2.9 %) required blood transfusion. Five patients (3.6 %) had Clavien Grade IIIa complications requiring an intervention for their management and none Grade IV or V. Despite the absence of evidence that non-calyceal percutaneous tracts could be a risk factor for complications, the concept of calyceal puncture has been worldwide adopted by PCNL surgeons as the sole safe percutaneous entrance into the collective system. Based on our experience, other pathways than the worldwide recognized rule, calyceal puncture, are possible and probably not as dangerous as has been previously stated.

Significance of off-hours in centralized primary percutaneous coronary intervention network.

PubMed

Becker, David; Soos, Pal; Berta, Balazs; Nagy, Andrea; Fulop, Gabor; Szabo, Gyorgy; Barczi, Gyorgy; Belicza, Eva; Martai, Istvan; Merkely, Béla

2009-10-01

To analyze the efficacy of a regionally organized primary percutaneous coronary intervention (PCI) network at the Heart Center, Semmelweis University Budapest, part of the "Budapest model," and the factors that influence it. In order to investigate the differences between regular and off-hours patient care in a 24-hour myocardial infarction primary care system, we included 1890 consecutive, unselected patients with ST-segment elevation myocardial infarction and followed them until at least one year. The follow-up was complete for all participants. The difference between regular hours and off-hours mortality was not significant either after 30 days (8.6% vs 8.8%, respectively) or after 1 year (15.3% vs 14.7%, respectively). The rate of patients with re-infarction, frequency of re-intervention, and major adverse cardiac events, including death, re-infarction, re-intervention, and coronary artery bypass graft surgery, were similar in both patient groups. The time delay between the onset of chest pain and arrival to the clinic was 5.9+/-5.8 hours (mean+/- standard deviation) during regular hours and 5.2+/-4.6 hours during off-hours (P=0.235). Direct transport caused significant decrease in the 30-day and 1-year mortality independent of duty time (7.2% vs 9.9%, P=0.027; 12.6% vs 16.7%, P=0.028; respectively). Centralized primary PCI network of the "Budapest model" achieved the same level of patient care during both off-hours and regular hours.

Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa.

PubMed

Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; van Wyk, Gavin; Vogt, Monica; Pahlana, Pearl; Nicol, Mark P; Meintjes, Graeme

2015-08-14

Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34-64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert). To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission. Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1-37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001). The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain.

The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: a randomized controlled trial.

PubMed

Yeung, Tracy Wing Yee; Chai, Joyce; Li, Raymond Hang Wun; Lee, Vivian Chi Yan; Ho, Pak Chung; Ng, Ernest Hung Yu

2014-11-01

Does endometrial injury in the cycle preceding ovarian stimulation for in vitro fertilization (IVF) improve the ongoing pregnancy rate in unselected subfertile women? Endometrial injury induced by endometrial aspiration in the preceding cycle does not improve the ongoing pregnancy rate in unselected subfertile women undergoing IVF. Implantation failure remains one of the major limiting factors for IVF success. Mechanical endometrial injury in the cycle preceding ovarian stimulation of IVF treatment has been shown to improve implantation and pregnancy rates in women with repeated implantation failures. There is limited data on unselected subfertile women, especially those undergoing their first IVF treatment. This randomized controlled trial recruited 300 unselected subfertile women scheduled for IVF/ICSI treatment between March 2011 and August 2013. Subjects were randomized into endometrial aspiration (EA) (n = 150) and non-EA (n = 150) groups according to a computer-generated randomization list. Subjects were recruited and randomized in the assisted reproductive unit at the University of Hong Kong. In the preceding cycle, women in the EA group underwent endometrial aspiration using a Pipelle catheter in mid-luteal phase. All women were treated with a cycle of IVF/ICSI. Pregnancy outcomes were compared. There were no significant differences in baseline or cycle characteristics between the groups. There were 209 subjects (69.7%) who were undergoing their first IVF cycle and 91 (30.3%) subjects who had repeated cycles. There was no significant difference in ongoing pregnancy rates [26.7% (40/150) versus 32.0% (48/150); RR 0.833 (95% CI 0.585-1.187), P = 0.375] in the EA and non-EA groups. The implantation rates [32.8% (67/204) versus 29.7% (68/229); RR 1.080 (95% CI 0.804-1.450), P = 0.120], clinical pregnancy rates [34.0% (51/150) versus 38.0 (57/150); RR 0.895 (95% CI 0.661-1.211), P = 0.548], miscarriage rates [30.3% (17/56) versus 18.6% (11/59), RR 1.628 (95% CI 0.838-3.164), P = 0.150] and multiple pregnancy rates [31.3% (16/51) versus 19.3% (11/57), RR 1.626 (95% CI 0.833-3.172), P = 0.154] were all comparable between the EA and non-EA groups. Subgroup analysis in women having first embryo transfer (n = 209) also demonstrated no significant difference in ongoing pregnancy rates, but for women undergoing repeated cycles (n = 91), the on-going pregnancy rate was significantly lower in the EA group than in the non-EA group. The study aimed at assessing an unselected population of subfertile women by recruiting consecutive women attending our fertility clinic. However, since the majority of the recruited women (69.7%) were having their first IVF treatments, the results may not be generalizable to all women undergoing IVF. Previous RCTs and meta-analyses have suggested improved pregnancy rates after pretreatment endometrial injury in women with repeated implantation failure. A recent RCT also showed increased pregnancy rates in unselected subfertile women after endometrial injury, although that study was terminated early and thus underpowered. Our study showed with adequate power that no significant improvement in pregnancy rates was observed after endometrial injury in unselected women undergoing IVF treatment. The study was supported by the Small Project Funding 201309176012 of the Committee on Research and Conference Grants, University of Hong Kong. The authors have nothing to disclose. HKCTR-1646 and NCT 01977976. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population.

PubMed

Nacu, Aliona; Kvistad, Christopher E; Naess, Halvor; Øygarden, Halvor; Logallo, Nicola; Assmus, Jörg; Waje-Andreassen, Ulrike; Kurz, Kathinka D; Neckelmann, Gesche; Thomassen, Lars

2017-02-01

The NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study) aimed to assess effect and safety of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population. Patients treated with intravenous thrombolysis within 4.5 hours after symptom onset were randomized 1:1 to either contrast-enhanced sonothrombolysis (CEST) or sham CEST. A visible arterial occlusion on baseline computed tomography angiography was not a prerequisite for inclusion. Pulse-wave 2 MHz ultrasound was given for 1 hour and contrast (SonoVue) as an infusion for ≈30 minutes. Magnetic resonance imaging and angiography were performed after 24 to 36 hours. Primary study end points were neurological improvement at 24 hours defined as National Institutes of Health Stroke Scale score 0 or reduction of ≥4 National Institutes of Health Stroke Scale points compared with baseline National Institutes of Health Stroke Scale and favorable functional outcome at 90 days defined as modified Rankin scale score 0 to 1. A total of 183 patients were randomly assigned to either CEST (93 patient) or sham CEST (90 patients). The rates of symptomatic intracerebral hemorrhage, asymptomatic intracerebral hemorrhage, or mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days was similar in the 2 groups both in the intention-to-treat analysis and in the per-protocol analysis. CEST is safe among unselected ischemic stroke patients with or without a visible occlusion on computed tomography angiography and with varying grades of clinical severity. There was, however, statistically no significant clinical effect of sonothrombolysis in this prematurely stopped trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01949961. © 2016 The Authors.

High prevalence of Anisakis simplex hypersensitivity and allergy in Sicily, Italy.

PubMed

Heffler, Enrico; Sberna, Maria Eva; Sichili, Stefania; Intravaia, Rossella; Nicolosi, Giuliana; Porto, Morena; Liuzzo, Maria Teresa; Picardi, Giuseppe; Fichera, Silvia; Crimi, Nunzio

2016-02-01

Anisakis simplex can elicit allergic reactions when ingested in raw or marinated fish. The prevalence of A simplex hypersensitivity and allergy in Sicily (Italy), an area where the consumption of raw or marinated fish is very common, has not been investigated thus far. To investigate the prevalence of A simplex sensitization and its clinical relevance in a large group of unselected patients. All consecutive patients referred to the authors' allergy clinic during a 22 month-period were included in the study, evaluated for sensitization to A simplex and other allergens depending on their clinical history, and investigated for allergic symptoms after the ingestion of raw or marinated fish. Of 3,419 patients screened, 527 (15.4%) were sensitized to A simplex and 29 of these (5.5% of sensitized patients) had a history of A simplex allergy. Approximately 30% of patients had mono-sensitization to A simplex. Co-sensitization to house dust mites or molds yielded an odds ratio of 1.98 or 3.18, respectively, for allergy to A simplex. A high prevalence of A simplex sensitization in a large proportion of patients with mono-sensitization was found, confirming that eating habits influence sensitization to this nematode. Allergic symptoms from A simplex ingestion in raw or marinated fish were quite frequent, with symptoms ranging from oral allergy syndrome to anaphylaxis. Patients sensitized to A simplex were more prone to have allergic symptoms when they had co-sensitization to house dust mites or molds, suggesting possible cross-reactive but clinically relevant allergens between these allergenic sources. Copyright © 2016. Published by Elsevier Inc.

Diagnosis of unstable angina pectoris has declined markedly with the advent of more sensitive troponin assays.

PubMed

D'Souza, Maria; Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S; Gerke, Oke; Larsen, Torben B; Diederichsen, Axel C P; Jangaard, Nikolaj; Diederichsen, Søren Z; Hosbond, Susanne; Hove, Jens; Thygesen, Kristian; Mickley, Hans

2015-08-01

Since the arrival of the universal definition of myocardial infarction more sensitive troponin assays have been developed. How these occurrences have influenced the proportions and clinical features of the components of acute coronary syndrome have not been studied prospectively in unselected hospital patients. During 2010 we evaluated all patients in whom cardiac troponin I had been measured at a single university hospital. The diagnosis of acute myocardial infarction (ST-elevation myocardial infarction [STEMI] or non-ST-elevation myocardial infarction [NSTEMI]) was established in cases of a rise and/or fall of cardiac troponin I together with cardiac ischemic features. Patients with unstable chest discomfort and cardiac troponin I values below the decision limit of myocardial infarction were diagnosed as having unstable angina pectoris. The definition of acute coronary syndrome included unstable angina pectoris, NSTEMI, and STEMI. Mortality data were obtained from the Danish Civil Personal Registration System. Of 3762 consecutive patients, 516 had acute coronary syndrome. Unstable angina pectoris was present in 7%, NSTEMI in 67%, and STEMI in 26%. The NSTEMI patients were older, more frequently women, and had more comorbidities than patients with unstable angina pectoris and STEMI. At median follow-up of 3.2 years 195 patients had died: 14% of unstable angina pectoris, 45% of NSTEMI, and 25% of STEMI patients. Age-adjusted log-rank statistics revealed differences in mortality: NSTEMI vs unstable angina pectoris (P = .0091) and NSTEMI vs STEMI (P = .0045). The application of the universal definition together with the use of a contemporary troponin assay seems to have reduced the proportion of patients with unstable angina pectoris to the benefit of patients with NSTEMI. Despite this, NSTEMI patients have a sustained higher mortality than patients with STEMI. Copyright © 2015 Elsevier Inc. All rights reserved.

Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy.

PubMed

Chen, Xin; Bernemann, Christof; Tolkach, Yuri; Heller, Martina; Nientiedt, Cathleen; Falkenstein, Michael; Herpel, Esther; Jenzer, Maximilian; Grüllich, Carsten; Jäger, Dirk; Sültmann, Holger; Duensing, Anette; Perner, Sven; Cronauer, Marcus V; Stephan, Carsten; Debus, Jürgen; Schrader, Andres Jan; Kristiansen, Glen; Hohenfellner, Markus; Duensing, Stefan

2018-04-01

Overexpression of the androgen receptor (AR) splice variant 7 (AR-V7) has recently been reported to be associated with resistance to antihormonal therapy. Herein, we address the question whether tumor cells with AR-V7 expression can be detected at the time of radical prostatectomy, that is, before long-term hormonal manipulation and castration resistance, and what the potential prognostic impact on the biochemical recurrence (BCR)-free survival may be. An anti-AR-V7 antibody was first validated in a training set of prostate cancer specimens by a comparison of AR-V7 protein to AR-V7 mRNA expression. We then analyzed nuclear AR-V7 protein expression in the primary tumors and lymph node metastases from 163 predominantly high-risk patients (cohort I) as well as the primary tumors from patients of a second, consecutive patient cohort (n = 238, cohort II) not selected for any clinicopathological features. Staining results were correlated to patient characteristics and BCR-free patient survival. High nuclear AR-V7 protein expression was detected in approximately 30%-40% of patients in cohort I and II at the time of radical prostatectomy. High baseline expression of nuclear AR-V7 protein was associated with an unfavorable BCR-free survival in the high-risk patient cohort I but not in the unselected consecutive cohort II. Remarkably, AR-V7 was an independent negative prognostic factor in high-risk prostate cancer patients of cohort I who were selected to receive adjuvant treatment. Prostate cancer cells with high nuclear AR-V7 protein expression can be detected in a substantial proportion of tumors at the time of radical prostatectomy. The presence of AR-V7-positive tumor cells is associated with an unfavorable prognosis for BCR-free survival in a high-risk patient cohort including a subgroup of patients selected to receive adjuvant therapy, in which AR-V7 was an independent negative prognosticator. Overexpression of nuclear AR-V7 protein hence identifies a subset of tumors with remarkably aggressive growth characteristics among clinically and histologically high-risk patients at the time of radical prostatectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

Submillisievert median radiation dose for coronary angiography with a second-generation 320-detector row CT scanner in 107 consecutive patients.

PubMed

Chen, Marcus Y; Shanbhag, Sujata M; Arai, Andrew E

2013-04-01

To (a) use a new second-generation wide-volume 320-detector row computed tomographic (CT) scanner to explore optimization of radiation exposure in coronary CT angiography in an unselected and consecutive cohort of patients referred for clinical purposes and (b) compare estimated radiation exposure and image quality with that from a cohort of similar patients who underwent imaging with a previous first-generation CT system. The study was approved by the institutional review board, and all subjects provided written consent. Coronary CT angiography was performed in 107 consecutive patients with a new second-generation 320-detector row unit. Estimated radiation exposure and image quality were compared with those from 100 consecutive patients who underwent imaging with a previous first-generation scanner. Effective radiation dose was estimated by multiplying the dose-length product by an effective dose conversion factor of 0.014 mSv/mGy ⋅ cm and reported with size-specific dose estimates (SSDEs). Image quality was evaluated by two independent readers. The mean age of the 107 patients was 55.4 years ± 12.0 (standard deviation); 57 patients (53.3%) were men. The median body mass index was 27.3 kg/m(2) (range, 18.1-47.2 kg/m(2)); however, 71 patients (66.4%) were overweight, obese, or morbidly obese. A tube potential of 100 kV was used in 97 patients (90.6%), single-volume acquisition was used in 104 (97.2%), and prospective electrocardiographic gating was used in 106 (99.1%). The mean heart rate was 57.1 beats per minute ± 11.2 (range, 34-96 beats per minute), which enabled single-heartbeat scans in 100 patients (93.4%). The median radiation dose was 0.93 mSv (interquartile range [IQR], 0.58-1.74 mSv) with the second-generation unit and 2.67 mSv (IQR, 1.68-4.00 mSv) with the first-generation unit (P < .0001). The median SSDE was 6.0 mGy (IQR, 4.1-10.0 mGy) with the second-generation unit and 13.2 mGy (IQR, 10.2-18.6 mGy) with the first-generation unit (P < .0001). Overall, the radiation dose was less than 0.5 mSv for 23 of the 107 CT angiography examinations (21.5%), less than 1 mSv for 58 (54.2%), and less than 4 mSv for 103 (96.3%). All studies were of diagnostic quality, with most having excellent image quality. Three of four image quality indexes were significantly better with the second-generation unit compared with the first-generation unit. The combination of a gantry rotation time of 275 msec, wide volume coverage, iterative reconstruction, automated exposure control, and larger x-ray power generator of the second-generation CT scanner provides excellent image quality over a wide range of body sizes and heart rates at low radiation doses. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122621/-/DC1. RSNA, 2013

Phase II trial of everolimus in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma.

PubMed

Geiger, Jessica L; Bauman, Julie E; Gibson, Michael K; Gooding, William E; Varadarajan, Prakash; Kotsakis, Athanasios; Martin, Daniel; Gutkind, Jorge Silvio; Hedberg, Matthew L; Grandis, Jennifer R; Argiris, Athanassios

2016-12-01

Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway. Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue. Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759-1764, 2016. © 2016 Wiley Periodicals, Inc.

Optimal electrocardiographic limb lead set for rapid emphysema screening

PubMed Central

Bajaj, Rishi; Chhabra, Lovely; Basheer, Zainab; Spodick, David H

2013-01-01

Background Pulmonary emphysema of any etiology has been shown to be strongly and quasidiagnostically associated with a vertical frontal P wave axis. A vertical P wave axis (>60 degrees) during sinus rhythm can be easily determined by a P wave in lead III greater than the P wave in lead I (bipolar lead set) or a dominantly negative P wave in aVL (unipolar lead set). The purpose of this investigation was to determine which set of limb leads may be better for identifying the vertical P vector of emphysema in adults. Methods Unselected consecutive electrocardiograms from 100 patients with a diagnosis of emphysema were analyzed to determine the P wave axis. Patients aged younger than 45 years, those not in sinus rhythm, and those with poor quality tracings were excluded. The electrocardiographic data were divided into three categories depending on the frontal P wave axis, ie, >60 degrees, 60 degrees, or <60 degrees, by each criterion (P amplitude lead III > lead I and a negative P wave in aVL). Results Sixty-six percent of patients had a P wave axis > 60 degrees based on aVL, and 88% of patients had a P wave axis > 60 degrees based on the P wave in lead III being greater than in lead I. Conclusion A P wave in lead III greater than that in lead I is a more sensitive marker than a negative P wave in aVL for diagnosing emphysema and is recommended for rapid routine screening. PMID:23378754

Feasibility and efficacy of the 2.5 L and 3.8 L impella percutaneous left ventricular support device during high-risk, percutaneous coronary intervention in patients with severe aortic stenosis.

PubMed

Spiro, Jon; Venugopal, Vinod; Raja, Yogesh; Ludman, Peter F; Townend, Jonathan N; Doshi, Sagar N

2015-05-01

Assessment of the feasibility and outcomes of the 2.5 L and 3.8 L Impella cardiac pump in patients with severe aortic stenosis (AS) and left ventricular impairment undergoing percutaneous revascularization (PCI) with or without balloon aortic valvuloplasty (BAV). We reviewed the clinical and procedural findings from a consecutive series of unselected patients with severe AS who underwent PCI during Impella support. In addition, we describe novel "balloon-assist" techniques that allowed implantation of Impella into the left ventricle (LV) when initial unassisted attempts failed. Five patients with severe AS were identified (four males, age 78.2 years, aortic valve area (AVA) 0.6 cm(2) , left ventricular ejection fraction (LVEF) 24 ± 5%, mean Society of Thoracic Surgeons (STS) mortality 11% (range 3-17%)). The Impella catheter traversed the aortic valve (AV) unassisted in only one patient, with four cases requiring balloon-assist techniques. All patients underwent planned revascularisation; mean procedure time 177 min (range 135-252 min), mean number of stents 3.4 (range 1-8), with three patients requiring rotational atherectomy. All procedures were well tolerated, with absence of arrhythmia, hypotension, pulmonary edema, stroke, or myocardial infarction. One patient died 48 hr post-PCI of multi-organ failure. The four remaining patients were well at 30 days. Implantation of the 2.5 and 3.8 L Impella appears feasible in patients with severe AS and left ventricle (LV) impairment. A balloon-assist technique may be used to facilitate device implantation when initial unassisted attempts fail. Improved hemodynamic stability may enhance the tolerability of lengthy and complex procedures. © 2014 Wiley Periodicals, Inc.

Prevalence of organic disease at colonoscopy in patients with symptoms compatible with irritable bowel syndrome: cross-sectional survey.

PubMed

Patel, Purav; Bercik, Premysl; Morgan, David G; Bolino, Carolina; Pintos-Sanchez, Maria Ines; Moayyedi, Paul; Ford, Alexander C

2015-07-01

Guidelines for the management of irritable bowel syndrome (IBS) encourage a positive diagnosis, but some evidence suggests organic disease may be missed unless investigations are performed. We examined yield of colonoscopy in a cohort of secondary care patients meeting criteria for IBS. Demographic data, symptoms and findings at colonoscopy were recorded prospectively in consecutive, unselected adults with gastrointestinal (GI) symptoms compatible with IBS according to the Rome III criteria. Prevalence of organic GI disease was compared between those meeting criteria for IBS, according to the presence or absence of co-existent alarm features, and by IBS subtype. A total of 559 patients met Rome III criteria for IBS, of whom 423 reported ≥1 alarm feature and 136 none. There was a significantly higher prevalence of organic GI disease among those reporting alarm features (117 [27.7%]), compared with those without (21 [15.4%]) (p = 0.002). In the latter group of 136 patients, Crohn's disease was the commonest finding (10 [7.4%] subjects), followed by coeliac disease (4 [2.9%] subjects), and microscopic colitis (3 [2.2%] subjects). Regardless of presence or absence of alarm features, patients with constipation-predominant IBS were less likely to exhibit organic GI disease than those with diarrhea-predominant or mixed IBS (12.7% vs. 32.1% and 23.8%, p = 0.006). One in six patients with symptoms compatible with IBS without alarm features in this selected group exhibited organic GI disease following investigation. Assessment of alarm features in a comprehensive history is vital to reduce diagnostic uncertainty that can surround IBS.

Pulmonary involvement in long-term mixed connective tissue disease: functional trends and image findings after 10 years.

PubMed

Kawano-Dourado, Leticia; Baldi, Bruno G; Kay, Fernando U; Dias, Olivia M; Gripp, Thais E H; Gomes, Paula S; Fuller, Ricardo; Caleiro, Maria T C; Kairalla, Ronaldo A; Carvalho, Carlos R R

2015-01-01

Interstitial lung disease (ILD) is highly prevalent in patients with mixed connective tissue disease (MCTD). However, little is known about the long-term progression of ILD in MCTD. The aims of this study were to describe pulmonary function test (PFT) and high-resolution computed tomography (HRCT) results in long-term MCTD patients, to measure changes in PFT and HRCT results over a 10-year period, and to ascertain correlations in functional and imaging data. In this retrospective cohort study, comparison between baseline and follow-up PFT and HRCT data was performed for 39 unselected consecutive MCTD patients. At baseline, 51% of the patients had abnormal PFTs. Forced vital capacity (FVC) was slightly reduced at baseline (77% of predicted), but remained stable after 10 years. A relative decrease of 15% in the diffusion capacity for carbon monoxide (DLCO) was detected (from 84% to 71% of predicted, p<0.001). The median lower lobes ILD-HRCT score progressed from 7.5% at baseline to 11.2% at follow-up (p=0.02), and findings of traction bronchiolectasis and honeycombing increased (p<0.05). A moderate negative correlation was observed between functional parameters and quantification of image findings. Functional and radiologic alterations suggestive of ILD in long-term MCTD patients are prevalent, mild, and progressed slightly over time. The most sensitive parameters for detecting subtle progression of ILD in MCTD patients are trends in DLCO, quantification of lower-lobes disease by HRCT (lower-lobes %ILD-HRCT score), and qualitative analysis of HRCT imaging.

External validity of the ARISTOTLE trial in real-life atrial fibrillation patients.

PubMed

Hägg, Lovisa; Johansson, Cecilia; Jansson, Jan-Håkan; Johansson, Lars

2014-10-01

Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility. We performed a cross-sectional study of an unselected population including 2274 patients in Skellefteå, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population. Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria. Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life. © 2014 John Wiley & Sons Ltd.

Comparison of beta blocker and digoxin alone and in combination for management of patients with atrial fibrillation and heart failure.

PubMed

Fauchier, Laurent; Grimard, Caroline; Pierre, Bertrand; Nonin, Emilie; Gorin, Laurent; Rauzy, Bruno; Cosnay, Pierre; Babuty, Dominique; Charbonnier, Bernard

2009-01-15

In patients with atrial fibrillation (AF) and heart failure (HF), beta blockers and digoxin reduce the ventricular rate, but controversy exists concerning how these drugs affect prognosis in this setting. This study compared the effects of beta blocker and digoxin on mortality in patients with both AF and HF. In a single-center institution, patients with AF and HF seen between January 2000 and January 2004 were identified and followed until September 2007. Of 1,269 consecutive patients with both AF and HF, 260 were treated with a beta blocker alone, 189 with beta blocker plus digoxin, 402 with digoxin alone, and 418 without beta blocker or digoxin (control group). During a follow-up of 881+/-859 days, 247 patients died. Compared with the control group, treatment with beta blocker was associated with a decreased mortality (relative risk=0.58, 95% confidence interval 0.40 to 0.85, p=0.005 for beta blocker alone and 0.59, 95% confidence interval 0.40 to 0.87, p=0.008 for beta blocker plus digoxin). By contrast, treatment with digoxin alone was not associated with a better survival (relative risk=0.97, 95% confidence interval 0.73 to 1.30, p=NS). Results remained significant after adjustment for potential confounders and similar when we considered, separately, HF with permanent or nonpermanent AF, presence or absence of coronary disease, and patients with decreased or preserved systolic function. In conclusion, in unselected patients with AF and HF, treatments with beta blocker alone or with beta blocker plus digoxin are associated with a similar decrease in the risk of death. Digoxin alone is associated with a worse survival chance, similar to that of patients without any rate control treatment.

Procalcitonin as a marker of micro-inflammation in hemodialysis.

PubMed

Conti, Giovanni; Amore, Alessandro; Chiesa, Monica; Mancuso, Domenico; Cirina, Paola; Mengozzi, Giulio; Santoro, Antonio; Coppo, Rosanna

2005-01-01

In searching for a rapid and sensitive test to detect micro-inflammation in patients on hemodialysis (HD), we measured serum procalcitonin (PCT) levels and made a comparison with other traditional markers such as C-reactive protein (CRP), serum amyloid (SAA) and homocysteine, considered related to vascular damage. We investigated 51 HD patients, without signs of infection, in basal conditions (during standard bicarbonate dialysis and unselected filters: X) and after 4 months of possibly more biocompatible treatments (on-line hemofiltration (HF) or HD with ultra-pure dialysate and biocompatible membranes: Y). Serum PCT (measured by immunoluminometric assay), CRP and SAA (nephelometric assay) and plasma homocysteine (measured by high performance liquid chromatography) concentrations were assessed at the beginning of dialysis (T0) and after 4 hr (T4). Patients on unselected dialysis displayed mean PCT values significantly increased after 4 hr of dialysis in comparison to those at the start of the sessions (XT4 1.56 +/- 3.93 vs. XT0 0.4 +/- 0.34 ng/mL; p < 0.05). The PCT levels detected after 4 hr of biocompatible treatments were significantly lower than those detected after 4 hr of unselected treatments (YT4 0.78 +/- 0.34 ng/mL; p < 0.05), even though the percentage of patients with positive PCT values (> 0.5 ng/mL) remained almost unchanged. No significant modification in mean levels or in the frequency of positive values was observed for CRP, SAA and homocysteine. After 4 months of highly biocompatible treatments, a reduction in intradialytic enhancements of all inflammation markers was detected. Our data support the conclusion that PCT is a more precise marker than other traditional tests to evaluate micro-inflammation and biocompatibility in HD.

Clinical outcomes in heart failure: report from a community hospital-based registry.

PubMed

Philbin, E F; Rocco, T A; Lindenmuth, N W; Ulrich, K; Jenkins, P L

1999-12-01

Most of the recent information on the prognosis of patients with heart failure has come from large clinical trials or tertiary care centers. This study reports current information from a community hospital-based heart failure registry. We compiled data from 2,906 unselected consecutive patients with heart failure who were admitted to 10 acute care community hospitals in New York State between 1995 and 1997. Patients were followed prospectively for 6 months after hospital discharge or until their death. The mean (+/- SI)) age of the sample was 76 +/- 11 years. The majority of the patients were women (56%) and most were white (95%). Hospital length of stay averaged 7.4 +/- 7.6 days; hospital charges averaged $7,460 +/- $6,114. Mortality during the index admission was 5%. Among the 2,508 patients for whom mortality or follow-up data were available, an additional 411 died during follow-up, for a cumulative 6-month mortality of 23%. Progressive pump failure was the predominant cause of death in the hospital and after discharge. Although mean functional class (on a 1 to 4 scale) improved from 3.4 +/- 0.7 at hospital admission to 2.3 +/- 0.9 at 1 month after discharge, 43% of patients had at least one hospital readmission during follow-up and 25% had at least one recurrent admission for heart failure. The mean time from index discharge to first rehospitalization was 60 +/- 56 days. In all, 55% of patients (1,370 of 2,508) were rehospitalized or died during the study period. Despite advances in the management of heart failure, patients recently hospitalized for this disorder remain at high risk of death, hospital readmission, and poor clinical outcome. Discovery or implementation of new or existing methods of prevention and treatment remain a high priority.

Application of the National Early Warning Score (NEWS) as a stratification tool on admission in an Italian acute medical ward: A perspective study.

PubMed

Spagnolli, Walter; Rigoni, Marta; Torri, Emanuele; Cozzio, Susanna; Vettorato, Elisa; Nollo, Giandomenico

2017-03-01

We aimed to assess the performance of the National Early Warning Score (NEWS) as tool for patient risk stratification at admission in an acute Internal Medicine ward and to ensure patient placement in ward areas with the required and most appropriate intensity of care. As secondary objective, we considered NEWS performance in two subgroups of patients: sudden cardiac events (acute coronary syndromes and arrhythmic events), and chronic respiratory insufficiency. We conducted a perspective cohort single centre study on 2,677 unselected patients consecutively admitted from July 2013 to March 2015 in the Internal Medicine ward of the hospital of Trento, Italy. The NEWS was mandatory collected on ward admission. We defined three risk categories for clinical deterioration: low score (NEWS 0-4), medium score (NEWS 5-6), and high score (NEWS≥7). Following adverse outcomes were considered: total and early (<72 hours) in-hospital mortality, urgent transfers to a higher intensity of care. A logistic regression model quantified the association between outcomes and NEWS. For patients with NEWS >4 vs patients with NEWS <4, the risk of early death increased from 12 to 36 times, total mortality from 3.5 to 9, and urgent transfers from 3.5 to 7. In patients with sudden cardiac events, lower scores were significantly associated with higher risk of transfer to a higher intensity of care. In patients affected by chronic hypoxaemia, adverse outcomes occurred less in medium and high score categories of NEWS. National Early Warning Score assessed on ward admission may enable risk stratification of clinical deterioration and can be a good predictor of in-hospital serious adverse outcomes, although sudden cardiac events and chronic hypoxaemia could constitute some limits. © 2017 John Wiley & Sons Ltd.

(1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies.

PubMed

Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

2016-04-19

Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1-3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77-510) vs. 50 (30-125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68-0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe.

(1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies

PubMed Central

Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

2016-01-01

Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1–3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77–510) vs. 50 (30–125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68–0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe. PMID:26910891

Time-Course Reduction in Patient Exposure to Radiation From Coronary Interventional Procedures: The Greater Paris Area Percutaneous Coronary Intervention Registry.

PubMed

Georges, Jean-Louis; Karam, Nicole; Tafflet, Muriel; Livarek, Bernard; Bataille, Sophie; Loyeau, Aurélie; Mapouata, Mireille; Benamer, Hakim; Caussin, Christophe; Garot, Philippe; Varenne, Olivier; Barbou, Franck; Teiger, Emmanuel; Funck, François; Karrillon, Gaëtan; Lambert, Yves; Spaulding, Christian; Jouven, Xavier

2017-08-01

The frequency of complex percutaneous coronary interventions (PCIs) has increased in the last few years, with a growing concern on the radiation dose received by the patients. Multicenter data from large unselected populations on patients' radiation doses during coronary angiography (CA) and PCI and temporal trends are lacking. This study sought to evaluate the temporal trends in patients' exposure to radiation from CA and PCI. Data were taken from the CARDIO-ARSIF registry that prospectively collects data on all CAs and PCIs performed in the 36 catheterization laboratories in the Greater Paris Area, the most populated regions in France with about 12 million inhabitants. Kerma area product and Fluoroscopy time from 152 684 consecutive CAs and 103 177 PCIs performed between 2009 and 2013 were analyzed. A continuous trend for a decrease in median [interquartile range] Kerma area product was observed, from 33 [19-55] Gy cm 2 in 2009 to 27 [16-44] Gy cm 2 in 2013 for CA ( P <0.0001), and from 73 [41-125] to 55 [31-91] Gy cm 2 for PCI ( P <0.0001). Time-course differences in Kerma area product remained highly significant after adjustment on Fluoroscopy time, PCI procedure complexity, change of x-ray equipment, and other patient- and procedure-related covariates. In a large patient population, a steady temporal decrease in patient radiation exposure during CA and PCI was noted between 2009 and 2013. Kerma area product reduction was consistent in all types of procedure and was independent of patient-related factors and PCI procedure complexity. © 2017 American Heart Association, Inc.

Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib.

PubMed

Seifert, Heike; Fisher, Rosalie; Martin-Liberal, Juan; Edmonds, Kim; Hughes, Peta; Khabra, Komel; Gore, Martin; Larkin, James

2016-04-01

The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials.

Ex-vivo expansion of CFU-GM and BFU-E in unselected PBMC cultures with Flt3L is enhanced by autologous plasma.

PubMed

Guo, M; Miller, W M; Papoutsakis, E T; Patel, S; James, C; Goolsby, C; Winter, J N

1999-01-01

Previous ex-vivo expansion studies in our laboratory, comparing unselected and CD34(+)-selected PBMC, have shown no advantage for CD34(+) cell selection, in terms of the expansion achieved. Our goal was to develop procedures for consistent generation of large numbers of hematopoietic progenitor and post-progenitor cells from unselected PBMC. Unselected PBMC, collected from cancer patients undergoing apheresis prior to high-dose chemotherapy and autologous stem cell rescue, were expanded ex vivo in static cultures, without a stromal layer, in the presence of Flt3 ligand (Flt3L), a recombinant GM-CSF/IL-3 fusion protein (PIXY321), G-CSF and GM-CSF for 10 days. The addition of 2% autologous plasma to this cytokine combination enhanced expansion of total cell numbers (3.2 fold versus 1.9 fold; p < 0.01), colony-forming units granulocyte-macrophage (CFU-GM) (22.0 fold versus 8.1 fold, p < 0.01) and burst-forming units erythroid (BFU-E) (17.6 fold versus 7.0 fold, 0.01 < p < 0.02). The optimal seeding density for a given specimen was inversely related to the frequency of CD34(+) cells in the sample. CFU-GM expansion with the Flt3L-containing cytokine cocktail was equivalent to that obtained with IL-3, IL-6, G-CSF and SCF, whether or not the cultures were supplemented with autologous plasma. In plasma-free cultures, BFU-E expansion was significantly higher with IL-3, IL-6, G-CSF and SCF than with Flt3L, PIXY321, G-CSF and GM-CSF. In the presence of autologous plasma, however BFU-E expansion was higher in the Flt3L-containing media. In comparison studies, autologous plasma suppressed BFU-E expansion in SCF-containing cultures. Consistent with our colony assay results, dual-parameter flow cytometric analysis of the expanded cell population revealed that supplementation with autologous plasma yielded a significant increase in the numbers of myeloid progenitors in Flt3L-containing cultures. Unselected PBMC from cancer patients can be effectively expanded ex vivo in Flt3L, PIXY321, G-CSF and GM-CSF, supplemented with autologous plasma, yielding high numbers of myeloid and erythroid progenitors.

Outcomes after cryoablation vs. radiofrequency in patients with paroxysmal atrial fibrillation: impact of pulmonary veins anatomy.

PubMed

Khoueiry, Z; Albenque, J-P; Providencia, R; Combes, S; Combes, N; Jourda, F; Sousa, P A; Cardin, C; Pasquie, J-L; Cung, T T; Massin, F; Marijon, E; Boveda, S

2016-09-01

Pulmonary vein isolation is the mainstay of treatment in catheter ablation of paroxysmal atrial fibrillation (AF). Cryoballoon ablation has been introduced more recently than radiofrequency ablation, the standard technique in most centres. Pulmonary veins frequently display anatomical variants, which may compromise the results of cryoballoon ablation. We aimed to evaluate the mid-term outcomes of cryoballoon ablation in an unselected population with paroxysmal AF from an anatomical viewpoint. Consecutive patients with paroxysmal AF who underwent a first procedure of cryoballoon ablation or radiofrequency were enrolled in this single-centre study. All patients underwent systematic standardized follow-up. Comparisons between radiofrequency and cryoballoon ablation (Arctic Front™ or Arctic Front Advance™) were performed regarding safety and efficacy endpoints, according to pulmonary vein (PV) anatomical variants. A total of 687 patients were enrolled (376 radiofrequency and 311 cryoballoon ablation). Baseline characteristics and distribution of PV anatomical variants were generally similar in the groups. After a mean follow-up of 14 ± 8 months, there was no difference in the incidence of relapse (17.0% cryoballoon ablation vs. 14.1% radiofrequency, P = 0.25). We observed no interaction of PV anatomical variants on mid-term procedural success. Our findings suggest that mid-term outcomes of cryoballoon ablation for paroxysmal AF ablation are similar to those of radiofrequency, regardless of PV anatomy. The presence of anatomical variants of PVs should not discourage the referral of patients with paroxysmal AF for cryoballoon ablation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Epidemiology of coeliac disease in a single centre in Southern Derbyshire 1958–2014

PubMed Central

Holmes, Geoffrey K T; Muirhead, A

2017-01-01

Objective To determine trends in diagnosis of coeliac disease (CD) in patients attending a single centre 1958–2014 and provide figures for prevalence and incidence in those born in Derby city over 4 decades. To explore a link between deprivation and prevalence and characteristics of CD in Asians. Design An unselected, consecutive series of 2410 adult patients with CD diagnosed in the catchment area of the Derby hospitals was identified. 1077 born within Derby city identified by postcodes was used to determine changes in prevalence and incidence over 4 decades. 191 patients were Asian. Population numbers were obtained from National Census information. Results In the quinquennium 2010–2014, 20 times more patients were diagnosed than during 1975–1979. 27% were diagnosed at ≥60 years. A paucity of diagnoses in young men was observed. Women were diagnosed most often in age band ≥35<45, 15 years earlier than men. The largest increase in diagnosis rates occurred in young women and the elderly. In 2014, overall prevalence was 1:188; women 1:138. 4.6% of the variation was attributed to deprivation. Diagnosis rates in Asians increased markedly although only 5% were diagnosed at ≥60 years, much lower than for whites. Conclusions The dramatic increase in number of patients with CD presents challenges for follow-up and new models of care need to be explored. Healthcare workers should be alert to the diagnosis in young men and elderly Asians. A dedicated coeliac clinic is an excellent facility to increase diagnosis rates. PMID:28761688

Higher prevalence of wheezing and lower FEV1 and FVC percent predicted in adults with sickle cell anaemia: A cross-sectional study.

PubMed

Musa, Baba M; Galadanci, Najibah A; Rodeghier, Mark; Debaun, Michael R

2017-02-01

Respiratory symptoms including wheezing are common in adults with sickle cell anaemia (SCA), even in the absence of asthma. However, the prevalence of spirometry changes and respiratory symptoms in adults with SCA is unknown. Using a cross-sectional study design, we tested the hypothesis that adults with SCA (cases) would have higher rates of lower airway obstruction and wheezing than those without SCA (controls) using the American Thoracic Society Division of Lung Diseases' questionnaire. Patients were adults with SCA aged between 18 and 65 years. Controls were consecutive unselected individuals without SCA who presented to an outpatient general medicine clinic. We enrolled 150 adults with SCA and 287 consecutive controls without SCA. The median age was 23.0 and 27.0 years for adults with and without SCA, respectively. Cases were more likely to report cough without a cold (35.0% vs 18.6%, P < 0.001), lower forced expiratory volume in 1 s (FEV 1 ) % predicted (70.1% vs 82.1%, P = 0.001) and lower forced vital capacity (FVC) % predicted (67.4% vs 74.9%, P = 0.001) than controls. In the multivariable model, wheezing was significantly associated with SCA status (OR = 1.69, 95% CI = 1.08-2.65, P = 0.024). Similarly, FEV 1 % predicted was significantly associated with SCA status and wheezing (P = 0.001 for both). Adults with SCA experience a higher rate of wheezing and impaired respiratory functions compared with controls from the same region. © 2016 Asian Pacific Society of Respirology.

Written pretest information and germline BRCA1/2 pathogenic variant testing in unselected breast cancer patients: predictors of testing uptake.

PubMed

Nilsson, Martin P; Nilsson, Erik D; Silfverberg, Barbro; Borg, Åke; Loman, Niklas

2018-06-06

This study aimed to evaluate predictors of testing uptake among unselected breast cancer patients who were offered germline BRCA1/2 testing in a prospective study. Pretest information was provided by a standardized invitation letter instead of in-person counseling. Data was abstracted from medical records. Using multivariate logistic regressions, predictors of testing uptake were analyzed. The overall uptake of testing was 67% (539 of 805 patients). Low uptake rates were found for patients aged ≥80 years (33%), and patients born outside of Europe (37%). In adjusted analysis, age ≥80 years (odds ratio [OR] 0.10; P = 0.002), psychiatric disorders (OR 0.46; P = 0.006), occupation requiring at least 3 years of university or college education (OR 2.03; P = 0.003), and breast cancer or ovarian cancer in first-degree or second-degree relatives (OR 1.66; P = 0.02) were independently associated with uptake of BRCA1/2 testing. Somatic comorbidity in patients aged <70 years was associated with lower testing uptake. Testing uptake varies across different subgroups according to patient-related factors that are readily available in the medical records. Knowledge about these factors enables health care professionals to identify patients who are less likely to pursue genetic testing.

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study.

PubMed

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, Sarah; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy; Jimenez-Linan, Mercedes; Sagoo, Gurdeep S; Abbs, Stephen; Hulbert-Williams, Nicholas; Pharoah, Paul; Crawford, Robin; Brenton, James D; Tischkowitz, Marc

2016-10-01

Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Reduced length of hospital stay after the introduction of a rapid recovery protocol for primary THA procedures.

PubMed

den Hartog, Yvon M; Mathijssen, Nina M C; Vehmeijer, Stephan B W

2013-10-01

Rapid recovery protocols after total hip arthroplasty (THA) have been introduced worldwide in the last few years and they have reduced the length of hospital stay. We show the results of the introduction of a rapid recovery protocol for primary THA for unselected patients in our large teaching hospital. In a retrospective cohort study, we included all 1,180 patients who underwent a primary THA between July 1, 2008 and June 30, 2012. These patients were divided into 3 groups: patients operated before, during, and after the introduction of the rapid recovery protocol. There were no exclusion criteria. All complications, re-admissions, and reoperations were registered and analyzed. The mean length of hospital stay decreased from 4.6 to 2.9 nights after the introduction of the rapid recovery protocol. There were no statistically significant differences in the rate of complications, re-admissions, or reoperations between the 3 groups. In a large teaching hospital, the length of hospital stay decreased after introduction of our protocol for rapid recovery after THA in unselected patients, without any increase in complications, re-admissions, or reoperation rate.

Acoustic (loudspeaker) facial EMG monitoring: II. Use of evoked EMG activity during acoustic neuroma resection.

PubMed

Prass, R L; Kinney, S E; Hardy, R W; Hahn, J F; Lüders, H

1987-12-01

Facial electromyographic (EMG) activity was continuously monitored via loudspeaker during eleven translabyrinthine and nine suboccipital consecutive unselected acoustic neuroma resections. Ipsilateral facial EMG activity was synchronously recorded on the audio channels of operative videotapes, which were retrospectively reviewed in order to allow detailed evaluation of the potential benefit of various acoustic EMG patterns in the performance of specific aspects of acoustic neuroma resection. The use of evoked facial EMG activity was classified and described. Direct local mechanical (surgical) stimulation and direct electrical stimulation were of benefit in the localization and/or delineation of the facial nerve contour. Burst and train acoustic patterns of EMG activity appeared to indicate surgical trauma to the facial nerve that would not have been appreciated otherwise. Early results of postoperative facial function of monitored patients are presented, and the possible value of burst and train acoustic EMG activity patterns in the intraoperative assessment of facial nerve function is discussed. Acoustic facial EMG monitoring appears to provide a potentially powerful surgical tool for delineation of the facial nerve contour, the ongoing use of which may lead to continued improvement in facial nerve function preservation through modification of dissection strategy.

Analysis of the Use of Extracorporeal Circulation on the In-Hospital Outcomes of Dialytic Patients Who Underwent Myocardial Revascularization Surgery.

PubMed

Miranda, Matheus; Branco, João Nelson Rodrigues; Vargas, Guilherme Flora; Hossne, Nelson Americo; Yoshimoto, Michele Costa; Fonseca, José Honorio de Almeida Palma da; Pestana, José Osmar Medina de Abreu; Buffolo, Enio

2016-12-01

Myocardial revascularization surgery is the best treatment for dyalitic patients with multivessel coronary disease. However, the procedure still has high morbidity and mortality. The use of extracorporeal circulation (ECC) can have a negative impact on the in-hospital outcomes of these patients. To evaluate the differences between the techniques with ECC and without ECC during the in-hospital course of dialytic patients who underwent surgical myocardial revascularization. Unicentric study on 102 consecutive, unselected dialytic patients, who underwent myocardial revascularization surgery in a tertiary university hospital from 2007 to 2014. Sixty-three patients underwent surgery with ECC and 39 without ECC. A high prevalence of cardiovascular risk factors was found in both groups, without statistically significant difference between them. The group "without ECC" had greater number of revascularizations (2.4 vs. 1.7; p <0.0001) and increased need for blood components (77.7% vs. 25.6%; p <0.0001) and inotropic support (82.5% vs 35.8%; p <0.0001). In the postoperative course, the group "without ECC" required less vasoactive drugs, (61.5% vs. 82.5%; p = 0.0340) and shorter time of mechanical ventilation (13.0 hours vs. 36,3 hours, p = 0.0217), had higher extubation rates in the operating room (58.9% vs. 23.8%, p = 0.0006), lower infection rates (7.6% vs. 28.5%; p = 0.0120), and shorter ICU stay (5.2 days vs. 8.1 days; p = 0.0054) as compared with the group with ECC surgery. No difference in mortality was found between the groups. Myocardial revascularization with ECC in patients on dialysis resulted in higher morbidity in the perioperative period in comparison with the procedure without ECC, with no difference in mortality though.

Laparoscopic Cholecystectomy and Incidental Carcinoma of the Extrahepatic Biliary Tree

PubMed Central

Raparelli, Luigi; Jover Navalon, Jose' Maria; Gomez, Ana Serantes; Azcoita, Mariano Moreno; Materia, Alberto; Basso, Nicola

2002-01-01

Background and Objectives: Gallbladder carcinoma is found in 0.2 % to 5% of patients undergoing cholecystectomy, and gallstones are found in 70% to 98% of patients with gallbladder carcinoma. Early diagnosis of carcinoma is difficult because of the absence of specific symptoms and the frequent association with chronic cholecystitis and gallstones. At present, laparoscopic cholecystectomy is the gold standard for the surgical treatment of symptomatic cholelithiasis and other benign gallbladder diseases. The aims of this study were to evaluate retrospectively the incidence of occasional and occult gallbladder carcinomas to ascertain the effect of laparoscopy on diagnosis and treatment of unexpected extrahepatic biliary tree carcinomas and to assess possible guidelines that can be taken into consideration when the problem is encountered. Methods: Clinical records of 3900 patients undergoing laparoscopic cholecystectomy were reviewed. Patients with occasional (intraoperative = Group A) or occult (postoperative = Group B) diagnosis of gallbladder or common bile duct carcinoma entered the study group. Follow-up data were obtained in June 2000. Results: A total of 14 patients (0.35%), 3 men and 11 women, mean age 60.8 years (range 37 to 73) with extra-hepatic biliary tree carcinoma were found. Occasional carcinomas occurred in 8 patients, occult carcinomas in 6. No deaths occurred in either group. The overall survival at mean follow-up of 30.5 months is 50%. Five patients are disease free, and 2 are alive with evidence of recurrence. Discussion: In 2 large series of unselected consecutive laparoscopic cholecystectomy, only 14 unsuspected malignant tumors of the extrahepatic biliary tree were found (0.35%). The limits of the preoperative workup and the difficult diagnosis of biliary tract carcinoma during laparoscopic cholecystectomy, has led to the present retrospective study and several significant recommendations. PMID:12500833

Temporal trends in critical events complicating HIV infection: 1999-2010 multicentre cohort study in France.

PubMed

Barbier, François; Roux, Antoine; Canet, Emmanuel; Martel-Samb, Patricia; Aegerter, Philippe; Wolff, Michel; Guidet, Bertrand; Azoulay, Elie

2014-12-01

Multicentre data are limited to appraise the management and prognosis of critically ill human immunodeficiency virus (HIV)-infected patients. We sought to describe temporal trends in demographic and clinical characteristics, indications for intensive care and outcome in this patient population. We conducted a cohort study of unselected HIV-infected patients admitted between 1999 and 2010 to 34 French ICUs contributing to the CUB-Réa prospective database. We included 6,373 consecutive patients. Over the 12-year period, increases occurred in median age (39 years in 1999-2001; 47 years in 2008-2010, p < 0.0001) and prevalence of comorbidities (notably malignancies, from 6.7 to 16.4%, p < 0.0001). Admissions for respiratory failure (39.8% overall), shock (8.1%) and coma (22.7%) decreased (p < 0.0001), while those for sepsis (19.3%) remained stable. The main final diagnoses were bacterial sepsis (24.6%) and non-bacterial acquired immune deficiency syndrome (AIDS)-defining diseases (steady decline from 26.0 to 17.5%, p < 0.0001). Patients increasingly received mechanical ventilation (from 42.9 to 54.0%) and renal replacement therapy (from 9.6 to 16.8%) (p < 0.0001), whereas vasopressor use remained stable (27.4%). ICU readmissions increased after 2004 (p < 0.0001). ICU and hospital mortality (17.6 and 26.9%, respectively) dropped markedly in the most severely ill patients requiring multiple life-sustaining therapies. Malignancies and chronic liver disease were heavily associated with hospital mortality by multivariate analysis, while the most common AIDS-defining complications (Pneumocystis jirovecii pneumonia, cerebral toxoplasmosis and tuberculosis) had no independent impact. Progressive ageing, increasing prevalence of comorbidities (mainly malignancies), a steady decline in AIDS-related illnesses and improved benefits from life-sustaining therapies were the main temporal trends in HIV-infected patients requiring ICU admission.

Location, sidedness, and sex distribution of intracranial arachnoid cysts in a population-based sample.

PubMed

Helland, Christian A; Lund-Johansen, Morten; Wester, Knut

2010-11-01

The aim of this study was to examine the distribution of intracranial arachnoid cysts in a large and unselected patient population with special emphasis on sidedness and sex distribution. In total, 299 patients with 305 arachnoid cysts were studied. These patients were consecutively referred to our department during a 20-year period from a well-defined geographical area with a stable population. There was a strong predilection (198 patients [66.2%]) for intracranial arachnoid cysts in the temporal fossa. Forty-two patients had cysts overlying the frontal convexity, 36 had cysts in the posterior fossa, and 23 patients had cysts in other, different locations. Of 269 cysts with clearly unilateral distribution, 163 were located on the left side and 106 on the right side. This difference resulted from the marked preponderance of temporal fossa cysts on the left side (left-to-right ratio 2.5:1; p < 0.0001 [adjusted < 0.0005]). For cysts in the cerebellopontine angle (CPA), there was preponderance on the right side (p = 0.001 [adjusted = 0.005]). Significantly more males than females had cysts in the temporal fossa (p = 0.002 [adjusted = 0.004]), whereas in the CPA a significant female preponderance was found (p = 0.016 [adjusted = 0.032]). For all other cyst locations, there was no difference between the 2 sexes. Arachnoid cysts have a strong predilection for the temporal fossa. There is a sex dependency for some intracranial locations of arachnoid cysts, with temporal cysts occurring more frequently in men, and CPA cysts found more frequently in women. Furthermore, there is a strong location-related sidedness for arachnoid cysts, independent of patient sex. These findings and reports from the literature suggest a possible genetic component in the development of some arachnoid cysts.

Influence of manual thrombus aspiration on left ventricular diastolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Ilić, Ivan; Stanković, Ivan; Vidaković, Radosav; Janićijević, Aleksandra; Cerović, Milivoje; Jovanović, Vladimir; Aleksić, Aleksandar; Obradović, Gojko; Nikolajević, Ivica; Kafedzić, Srdjan; Milicević, Dusan; Kusić, Jovana; Putniković, Biljana; Nesković, Aleksandar N

2016-01-01

Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients'status was assessed by an office visit or telephone interview. Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n = 217). Groups had similar total ischemic time (319 ± 276 vs. 333 ± 372 min; p = 0.665), but TA+ group had higher maximum values of troponin I (39.5 ± 30.5 vs. 27.6 ± 26.9 ng/ml; p < 0.001). The echocardiography revealed similar left ventricular volumes and systolic function, but TA+ group had significantly higher incidence of E/e' > 15, as a marker of severe diastolic dysfunction' (TA+ 23.1% vs. TA- 15.2%; p = 0.050). During average follow-up of 14 ± 5 months, major adverse cardiac/cerebral events occurred at the similar rate (log rank p = 0.867). Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn't influence the incidence of major adverse cardiovascular events.

The evolution of analgesia in an 'accelerated' recovery programme for resectional laparoscopic colorectal surgery with anastomosis.

PubMed

Zafar, N; Davies, R; Greenslade, G L; Dixon, A R

2010-02-01

The study set out to analyse the outcomes of an evolving accelerated recovery programme after laparoscopic colorectal resection (LCR). The results of a prospective electronic database (March 2000 - April 2008) were analysed. There were 353 consecutive patients undergoing 'three port' high anterior resection (AR) (237 without covering stoma) and 166 a right hemicolectomy (RHC). One hundred thirty-eight had postoperative analgesia using paracetamol IV and oral analgesia (IVP); 27 (16.3%) received additional parenteral morphine and were excluded. Patient controlled morphine analgesia (PCA) was used in 138. Transversus abdominis plane (TAP) blocks, supplemented by IV paracetamol and oral analgesia were used in the last 50 patients. The time to the resumption of diet was significantly reduced with TAP analgesia (median 12 h) and IVP (median 12 h) compared with PCA median (36 h) (chi(2) = 143; 4df: P < 0.001). The postoperative hospital stay was significantly reduced with TAP analgesia (median 2 days) and IVP (median 3 days) compared with PCA (median 5 days); chi(2) = 73; 2df: P < 0.001. Seventeen (34%) TAP and nine (6.5%) IVP patients were discharged within 24 h of surgery compared with no patient in the PCA group. Ninety-three per cent of PCA, 35% IVP and 10% TAP patients were discharged in more than 3 days. The movement towards 'accelerated recovery' was not associated with any increased risk of urinary retention, return to theatre, readmission and/or 30 day mortality. Laparoscopic surgery utilizing IV paracetamol and TAP blocks for postoperative analgesia aids safe effective 'accelerated recovery' in an unselected patient population undergoing right hemicolectomy and high anterior resection. Routine epidural anaesthesia is unnecessary for LCR. Morphine PCA is associated with delayed recovery.

Developmental differences according to age at onset in juvenile bipolar disorder.

PubMed

Masi, Gabriele; Perugi, Giulio; Millepiedi, Stefania; Mucci, Maria; Toni, Cristina; Bertini, Nicoletta; Pfanner, Chiara; Berloffa, Stefano; Pari, Cinzia

2006-12-01

This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome. A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study. Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups. Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.

Can combined use of low-level lasers and hyaluronic acid injections prolong the longevity of degenerative knee joints?

PubMed Central

Ip, David; Fu, Nga Yue

2015-01-01

Background This study evaluated whether half-yearly hyaluronic acid injection together with low-level laser therapy in addition to standard conventional physical therapy can successfully postpone the need for joint replacement surgery in elderly patients with bilateral symptomatic tricompartmental knee arthritis. Methods In this prospective, double-blind, placebo-controlled study, 70 consecutive unselected elderly patients with bilateral tricompartmental knee arthritis were assigned at random to either one of two conservative treatment protocols to either one of the painful knees. Protocol A consisted of conventional physical therapy plus a sham light source plus saline injection, and protocol B consisted of protocol A with addition of half-yearly hyaluronic acid injection as well as low-level laser treatment instead of using saline and a sham light source. Treatment failure was defined as breakthrough pain necessitating joint replacement. Results Among the 140 painful knees treated with either protocol A or protocol B, only one of the 70 painful knees treated by protocol B required joint replacement, whereas 15 of the 70 painful knees treated by protocol A needed joint replacement surgery (P<0.05). Conclusion We conclude that half-yearly hyaluronic acid injections together with low-level laser therapy should be incorporated into the standard conservative treatment protocol for symptomatic knee arthritis, because it may prolong the longevity of the knee joint without the need for joint replacement. PMID:26346122

Refined 4-group classification of left ventricular hypertrophy based on ventricular concentricity and volume dilatation outlines distinct noninvasive hemodynamic profiles in a large contemporary echocardiographic population.

PubMed

Barbieri, Andrea; Rossi, Andrea; Gaibazzi, Nicola; Erlicher, Andrea; Mureddu, Gian Francesco; Frattini, Silvia; Faden, Giacomo; Manicardi, Marcella; Beraldi, Monica; Agostini, Francesco; Lazzarini, Valentina; Moreo, Antonella; Temporelli, Pier Luigi; Faggiano, Pompilio

2018-05-23

Left ventricular hypertrophy (LVH) may reflect a wide variety of physiologic and pathologic conditions. Thus, it can be misleading to consider all LVH to be homogenous or similar. Refined 4-group classification of LVH based on ventricular concentricity and dilatation may be identified. To determine whether the 4-group classification of LVH identified distinct phenotypes, we compared their association with various noninvasive markers of cardiac stress. Cohort of unselected adult outpatients referred to a seven tertiary care echocardiographic laboratory for any indication in a 2-week period. We evaluated the LV geometric patterns using validated echocardiographic indexation methods and partition values. Standard echocardiography was performed in 1137 consecutive subjects, and LVH was found in 42%. The newly proposed 4-group classification of LVH was applicable in 88% of patients. The most common pattern resulted in concentric LVH (19%). The worst functional and hemodynamic profile was associated with eccentric LVH and those with mixed LVH had a higher prevalence of reduced EF than those with concentric LVH (P < .001 for all). The new 4-group classification of LVH system showed distinct differences in cardiac function and noninvasive hemodynamics allowing clinicians to distinguish different LV hemodynamic stress adaptations in patients with LVH. © 2018 Wiley Periodicals, Inc.

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru.

PubMed

Abugattas, J; Llacuachaqui, M; Allende, Y Sullcahuaman; Velásquez, A Arias; Velarde, R; Cotrina, J; Garcés, M; León, M; Calderón, G; de la Cruz, M; Mora, P; Royer, R; Herzog, J; Weitzel, J N; Narod, S A

2015-10-01

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation-positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic-related mutations in BRCA1 associated with an increased risk of ovarian cancer.

PubMed

Shi, Tingyan; Wang, Pan; Xie, Caixia; Yin, Sheng; Shi, Di; Wei, Congchong; Tang, Wenbin; Jiang, Rong; Cheng, Xi; Wei, Qingyi; Wang, Qing; Zang, Rongyu

2017-05-01

BRCA1/2 are cancer predisposition genes involved in hereditary breast and ovarian cancer (HBOC). Mutation carriers display an increased sensitivity to inhibitors of poly(ADP-ribose) polymerase (PARP). Despite a number of small-size hospital-based studies being previously reported, there is not yet, to our knowledge, precise data of BRCA1/2 mutations among Chinese ovarian cancer patients. We performed a multicenter cohort study including 916 unselected consecutive epithelial ovarian cancer (EOC) patients from eastern China to screen for BRCA1/2 mutations using the next-generation sequencing approach. A total of 153 EOC patients were found to carry pathogenic germline mutations in BRCA1/2, accounting for an overall mutation incidence of 16.7% with the predominance in BRCA1 (13.1%) compared with BRCA2 (3.9%). We identified 53 novel pathogenic mutations, among which the c.283_286delCTTG and the c.4573C > T of BRCA1 were both found in two unrelated patients. More importantly, the most common mutation found in this study, c.5470_5477del8 was most likely to be Chinese population-related without an apparent founder origin. This hot-spot mutation was presumably associated with an increased risk of ovarian cancer. Taken together, germline BRCA1/2 mutations were common in Chinese EOC patients with distinct mutational spectrum compared to Western populations. Our study contributes to the current understanding of BRCA1/2 mutation prevalence worldwide. We recommend BRCA1/2 genetic testing to all Chinese women diagnosed with EOC to identify HBOC families, to provide genetic counseling and clinical management for at-risk relatives. Mutation carriers may also benefit from PARP-targeted therapies. © 2017 UICC.

High prevalence of insomnia and hypnotic use in patients visiting their general practitioner.

PubMed

Bjorvatn, Bjørn; Meland, Eivind; Flo, Elisabeth; Mildestvedt, Thomas

2017-02-01

Sleep problems are common in the general population, but there are few prevalence studies among patients visiting their GP. Since sleep problems frequently co-occur with existing psychological and somatic conditions, the prevalence is likely to be higher in patients visiting their GPs compared to the prevalence in the general population. To estimate the prevalence of insomnia [based on the Diagnostic and Statistical Manual for Mental disorders (DSM)-version IV] and hypnotic use among patients in general practice and to evaluate whether the prevalence depended on sex and age. Questionnaire data were collected by 66 medical students while deployed in different general practices during their last year of school. A total of 1346 (response rate 74%) consecutive and unselected patients visiting their GPs answered the validated Bergen Insomnia Scale (BIS) and single questions on self-reported sleep problems and hypnotic use. The prevalence of insomnia according to BIS was 53.6%. Sleep problems (based on the single question) were self-reported by 55.8%, with 18.0% reporting to experience sleep problems a lot/very much. Hypnotic use was reported by 16.2% (daily use by 5.5%). Insomnia and hypnotic use were all more prevalent in females compared with males. Hypnotic use increased with age, whereas the prevalence of insomnia was highest in the younger age groups. Insomnia and hypnotic use were very prevalent among patients visiting their GPs. As insomnia can be effectively treated, we maintain that the diagnosis has a high pay-off and should earn greater awareness in GP's diagnostic evaluation and management. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients.

PubMed

Adlbrecht, Christopher; Hülsmann, Martin; Strunk, Guido; Berger, Rudolf; Mörtl, Deddo; Struck, Joachim; Morgenthaler, Nils G; Bergmann, Andreas; Jakowitsch, Johannes; Maurer, Gerald; Lang, Irene M; Pacher, Richard

2009-04-01

The identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or non-ischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional-pro-adrenomedullin (MR-proADM) and C-terminal-pro-endothelin-1 (CT-proET-1) in outpatients with CHF. We measured plasma MR-proADM and CT-proET-1 levels in 786 consecutive CHF outpatients and compared them with B-type natriuretic peptide (BNP) levels. At 24-month follow-up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA > II, left ventricular ejection fraction (LVEF), MR-proADM, CT-proET-1, and BNP as possible predictors revealed that MR-proADM levels [hazard ratio (HR) = 1.77, P < 0.001] in addition to age (HR = 1.02, P = 0.004), ejection fraction (HR = 0.98, P = 0.004), and NYHA > II (HR = 1.86, P < 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA-stage, MR-proADM (HR = 2.12, P < 0.001) and LVEF (HR = 0.96, P = 0.006) were significant markers, but only in patients with mild/moderate CHF. Our data suggest that MR-proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non-ischaemic CHF patients.

Weight gain following treatment of hyperthyroidism.

PubMed

Dale, J; Daykin, J; Holder, R; Sheppard, M C; Franklyn, J A

2001-08-01

Patients frequently express concern that treating hyperthyroidism will lead to excessive weight gain. This study aimed to determine the extent of, and risk factors for, weight gain in an unselected group of hyperthyroid patients. We investigated 162 consecutive hyperthyroid patients followed for at least 6 months. Height, weight, clinical features, biochemistry and management were recorded at each clinic visit. Documented weight gain was 5.42 +/- 0.46 kg (mean +/- SE) and increase in BMI was 8.49 +/- 0.71%, over a mean 24.2 +/- 1.6 months. Pre-existing obesity, Graves' disease causing hyperthyroidism, weight loss before presentation and length of follow-up each independently predicted weight gain. Patients treated with thionamides or radioiodine gained a similar amount of weight (thionamides, n = 87, 5.16 +/- 0.63 kg vs. radioiodine, n = 62, 4.75 +/- 0.57 kg, P = 0.645), but patients who underwent thyroidectomy (n = 13) gained more weight (10.27 +/- 2.56 kg vs. others, P = 0.007). Development of hypothyroidism (even transiently) was associated with weight gain (never hypothyroid, n = 102, 4.57 +/- 0.52 kg, transiently hypothyroid, n = 29, 5.37 +/- 0.85 kg, on T4, n = 31, 8.06 +/- 1.42 kg, P = 0.014). This difference remained after correcting for length of follow-up. In the whole cohort, weight increased by 3.95 +/- 0.40 kg at 1 year (n = 144) to 9.91 +/- 1.62 kg after 4 years (n = 27) (P = 0.008), representing a mean weight gain of 3.66 +/- 0.44 kg/year. We have demonstrated marked weight gain after treatment of hyperthyroidism. Pre-existing obesity, a diagnosis of Graves' disease and prior weight loss independently predicted weight gain and weight continued to rise with time. Patients who became hypothyroid, despite T4 replacement, gained most weight.

Coronary angioplasty with second generation Monorail catheters.

PubMed

Pande, A K; Meier, B; Urban, P; Villavicencio, R; de la Serna, F; Moles, V

1991-07-01

The Monorail system (Schneider) consists of a balloon catheter in which the guidewire passes through the balloon itself, exits the catheter proximal to the balloon, and runs alongside its small shaft (3 French) through the length of the guiding catheter. It offers distinct advantages over conventional systems of coronary angioplasty. It facilitates contrast injections and permits rapid balloon exchanges. This system was used for coronary angioplasty in 273 unselected consecutive patients (age 59 +/- 10, mean 35 to 73 years). There were 216 patients (84%) undergoing single-vessel and 57 patients (16%) with multi-vessel coronary angioplasty. A total of 335 coronary stenoses were dilated, which included 35 total occlusions. The size of balloon used ranged from 2.0 to 4.25 mm (3.0 +/- 0.5 mm) and the severity of stenosis was 85 +/- 11%. Technical success was defined as a residual stenosis of less than 50% as determined angiographically. Clinical success was defined as technical success, and absence of a major inhospital complication defined as absence of myocardial infarction, lack of need for coronary arterial bypass surgery, and survival. The Monorail system was technically successful in 294/300 stenotic lesions (98%). It was clinically successful for 281 lesions (94%). Of the 35 total occlusions, technical success was obtained in 25 (71%). The residual stenosis of successful cases was 26 +/- 21%. The Monorail system was also successful in 5 patients with stenosis of more than 90% in whom conventional systems failed. The complications included acute occlusion causing acute myocardial infarction in 13 cases (5%), emergency coronary arterial bypass surgery in 1 patient (0.4%), and death in 4 patients (1.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Epidermal growth factor receptor in non-small cell lung cancer

PubMed Central

2015-01-01

Following the identification of a group of patients in the initial tyrosine kinase inhibitor (TKI) trials for lung cancer, there has been detailed focus on which patients may benefit from inhibitor therapy. This article reviews the background, genetics and prevalence of epidermal growth factor mutations in non-small cell lung cancer (NSCLC). Additionally, the prevalence in unselected patients is compared against various other reviews. PMID:25870793

Management of patients during hunger strike and refeeding phase.

PubMed

Eichelberger, M; Joray, M L; Perrig, M; Bodmer, M; Stanga, Z

2014-01-01

Hunger strikers resuming nutritional intake may develop a life-threatening refeeding syndrome (RFS). Consequently, hunger strikers represent a core challenge for the medical staff. The objective of the study was to test the effectiveness and safety of evidence-based recommendations for prevention and management of RFS during the refeeding phase. This was a retrospective, observational data analysis of 37 consecutive, unselected cases of prisoners on a hunger strike during a 5-y period. The sample consisted of 37 cases representing 33 individual patients. In seven cases (18.9%), the hunger strike was continued during the hospital stay, in 16 episodes (43.2%) cessation of the hunger strike occurred immediately after admission to the security ward, and in 14 episodes (37.9%) during hospital stay. In the refeed cases (n = 30), nutritional replenishment occurred orally, and in 25 (83.3%) micronutrients substitutions were made based on the recommendations. The gradual refeeding with fluid restriction occurred over 10 d. Uncomplicated dyselectrolytemia was documented in 12 cases (40%) within the refeeding phase. One case (3.3%) presented bilateral ankle edemas as a clinical manifestation of moderate RFS. Intensive medical treatment was not necessary and none of the patients died. Seven episodes of continued hunger strike were observed during the entire hospital stay without medical complications. Our data suggested that seriousness and rate of medical complications during the refeeding phase can be kept at a minimum in a hunger strike population. This study supported use of recommendations to optimize risk management and to improve treatment quality and patient safety in this vulnerable population. Copyright © 2014 Elsevier Inc. All rights reserved.

Inductive learning of thyroid functional states using the ID3 algorithm. The effect of poor examples on the learning result.

PubMed

Forsström, J

1992-01-01

The ID3 algorithm for inductive learning was tested using preclassified material for patients suspected to have a thyroid illness. Classification followed a rule-based expert system for the diagnosis of thyroid function. Thus, the knowledge to be learned was limited to the rules existing in the knowledge base of that expert system. The learning capability of the ID3 algorithm was tested with an unselected learning material (with some inherent missing data) and with a selected learning material (no missing data). The selected learning material was a subgroup which formed a part of the unselected learning material. When the number of learning cases was increased, the accuracy of the program improved. When the learning material was large enough, an increase in the learning material did not improve the results further. A better learning result was achieved with the selected learning material not including missing data as compared to unselected learning material. With this material we demonstrate a weakness in the ID3 algorithm: it can not find available information from good example cases if we add poor examples to the data.

Absence of Bacteria on Coronary Angioplasty Balloons from Unselected Patients: Results with Use of a High Sensitivity Polymerase Chain Reaction Assay

PubMed Central

Hansen, Gorm Mørk; Nilsson, Martin; Nielsen, Claus Henrik; Holmstrup, Palle; Helqvist, Steffen; Tolker-Nielsen, Tim; Givskov, Michael; Hansen, Peter Riis

2015-01-01

Periodontitis is a chronic, bacterially-induced inflammatory disease of the tooth-supporting tissues, which may result in transient bacteremia and a systemic inflammatory response. Periodontitis is associated with coronary artery disease independently of established cardiovascular risk factors, and translocation of bacteria from the oral cavity to the coronary arteries may play a role in the development of coronary artery disease. Very few studies have used angioplasty balloons for in vivo sampling from diseased coronary arteries, and with varying results. Therefore, the aim of this study was to assess if bacterial DNA from primarily oral bacteria could be detected on coronary angioplasty balloons by use of an optimized sampling process combined with an internally validated sensitive polymerase chain reaction (PCR) assay. Coronary angioplasty balloons and control samples from a total of 45 unselected patients with stable angina, unstable angina/non-ST elevation myocardial infarction, and ST-elevation myocardial infarction (n = 15 in each group) were collected and analyzed using a PCR assay with high sensitivity and specificity for 16S rRNA genes of the oral microbiome. Despite elimination of extraction and purification steps, and demonstration of sensitivity levels of 25–125 colony forming units (CFU), we did not detect bacterial DNA from any of the coronary angioplasty balloons. A subsequent questionnaire indicated that the prevalence of periodontitis in the study cohort was at least 39.5%. Although coronary angioplasty balloons are unlikely to be useful for detection of bacteria with current PCR techniques in unselected patients with coronary artery disease, more studies are warranted to determine the extent to which bacteria contribute to atherosclerosis and its clinical manifestations and whether the presence of bacteria in the arteries is a transient phenomenon. PMID:26695491

Subclinical Early Post-Traumatic Seizures Detected by Continuous EEG Monitoring in a Consecutive Pediatric Cohort

PubMed Central

Arndt, Daniel H; Lerner, Jason T; Matsumoto, Joyce H; Madikians, Andranik; Yudovin, Sue; Valino, Heather; McArthur, David L; Wu, Joyce Y; Leung, Michelle; Buxley, Farzad; Szeliga, Conrad; Van Hirtum-Das, Michele; Sankar, Raman; Brooks-Kayal, Amy; Giza, Christopher C

2015-01-01

Summary Purpose Traumatic brain injury (TBI) is an important cause of morbidity and mortality in children and early post-traumatic seizures (EPTS) are a contributing factor to ongoing acute damage. Continuous video EEG monitoring (cEEG) was utilized to assess the burden of clinical and electrographic EPTS. Methods Eighty-seven consecutive, unselected (mild – severe), acute TBI patients requiring pediatric intensive care unit (PICU) admission at 2 academic centers were prospectively monitored with cEEG per established clinical TBI protocols. Clinical and subclinical seizures and status epilepticus (SE, clinical and subclinical) were assessed for their relation to clinical risk factors and short-term outcome measures. Key findings Of all patients, 42.5% (37/87) had seizures. Younger age (p=0.002) and mechanism (abusive head trauma - AHT, p<0.001) were significant risk factors. Subclinical seizures occurred in 16.1% (14/87), 6 of whom had only subclinical seizures. Risk factors for subclinical seizures included: younger age (p<0.001), AHT (p<0.001) and intraaxial bleed (p<0.001). Status Epilepticus (SE) occurred in 18.4% (16/87) with risk factors including: younger age (p<0.001), AHT (p<0.001), and intraaxial bleed (p=0.002). Subclinical SE was detected in 13.8% (12/87) with significant risk factors including: younger age (p<0.001), AHT (p=0.001), and intraaxial bleed (p=0.004). Subclinical seizures were associated with lower discharge KOSCHI score (p=0.002). SE and subclinical SE were associated with increased hospital length of stay (p=0.017 and p=0.041 respectively) and lower hospital discharge KOSCHI (p=0.007 and p=0.040 respectively). Significance cEEG monitoring significantly improves detection of seizures/SE and is the only way to detect subclinical seizures/SE. cEEG may be indicated after pediatric TBI, particularly in younger children, AHT cases, and those with intraaxial blood on CT. PMID:24032982

Using Serum α-Fetoprotein for Prognostic Prediction in Patients with Hepatocellular Carcinoma: What is the Most Optimal Cutoff?

PubMed Central

Hsu, Chia-Yang; Liu, Po-Hong; Lee, Yun-Hsuan; Hsia, Cheng-Yuan; Huang, Yi-Hsiang; Lin, Han-Chieh; Chiou, Yi-You; Lee, Fa-Yauh; Huo, Teh-Ia

2015-01-01

Background and Aims The prognostic ability of α-fetoprotein (AFP) for patients with hepatocellular carcinoma (HCC) was examined by using different cutoff values. The optimal AFP cutoff level is still unclear. Methods A total of 2579 HCC patients were consecutively enrolled in Taiwan, where hepatitis B is the major etiology of chronic liver disease. Four frequently used AFP cutoff levels, 20, 200, 400, 1000 ng/mL, were investigated. One-to-one matched pairs between patients having AFP higher and lower than the cutoffs were selected by using the propensity model. The adjusted hazard ratios of survival difference were calculated with Cox proportional hazards model. Results Patients with a higher AFP level were associated with more severe cirrhosis, more frequent vascular invasion, higher tumor burden and poorer performance status (all p<0.0001). In the propensity model, 4 groups of paired patients were selected, and there was no difference found in the comparison of baseline characteristics (all p>0.05). Patients with AFP <20 ng/mL had significantly better long-term survival than patients with AFP ≧20 ng/mL (p<0.0001), and patients with AFP <400 ng/mL had significantly better overall outcome than patients with AFP ≧400 ng/mL (p = 0.0186). There was no difference of long-term survival between patients divided by AFP levels of 200 and 1000 ng/mL. The adjusted hazard ratios of AFP ≧20 ng/mL and AFP ≧400 ng/mL were 1.545 and 1.471 (95% confidence interval: 1.3–1.838 and 1.178–1.837), respectively. Conclusions This study shows the independently predictive ability of baseline serum AFP level in HCC patients. AFP levels of 20 and 400 ng/mL are considered feasible cutoffs to predict long-term outcome in unselected HCC patients. PMID:25738614

Benefits of pre-emptive analgesia by local infiltration at day-case general anaesthetic open inguinal hernioplasty.

PubMed

Radwan, R W; Gardner, A; Jayamanne, H; Stephenson, B M

2018-03-15

Introduction The open prosthetic repair of inguinal hernias under local anaesthesia (LA) is well established, with the concept of intraoperative 'pre-emptive analgesia' evolving so that patients are as comfortable as possible. We used a peri-incisional LA solution in patients undergoing day-case inguinal hernioplasty under general anaesthesia (GA) and recorded use of analgesia in the immediate postoperative period. Methods In this observational cohort study, 100 consecutive unselected men underwent open inguinal hernia repair as a day case. Of these, 75 underwent repair under GA and 25 with peri-incisional LA solution (equal mixture of 0.5% bupivacaine and 1% lignocaine with 1:200,000 adrenaline). Analgesia prescribed at induction, for maintenance and after cessation of anaesthesia was scored in accordance with the World Health Organization (WHO) analgesic ladder. Results The median age in the GA group was 59 years (range: 25-89 years) and in the GA+LA group, it was 62 years (range: 27-88 years). Of the 100 patients, 82 underwent a mesh plug repair by seven surgeons whereas 18 underwent a flat (Lichtenstein) mesh repair by two surgeons. WHO analgesic induction and postoperative scores were significantly lower in the GA+LA group (p=0.034 and p<0.001 respectively). There was also a significant difference in use of postoperative antiemetics (23% vs 0% in the GA only and GA+LA cohorts respectively, p=0.020). Six patients (8%) in the GA group failed day-case discharge criteria. Conclusions Patients undergoing contemporary day-case GA inguinal hernioplasty with pre-emptive LA solution infiltration require lower levels of postoperative opioid analgesia and antiemetics. These cases are less likely to fail discharge criteria for planned day surgery.

Use of systemic antifungals in daily clinical practice in the haematology and oncology setting: results of a prospective observational analysis.

PubMed

Metzke, Barbara; Neubauer, Werner Christian; Hieke, Stefanie; Jung, Manfred; Wäsch, Ralph; Engelhardt, Monika

2012-09-01

To assess the role of systemic antifungal drugs as well as the frequency of potential drug interactions and adverse drug events of commonly used antifungals in an unselected haematology/oncology patient cohort. A prospective analysis was performed in our haematology/oncology department between October 2006 and September 2009. Data were obtained from 250 consecutive patients who received treatment and/or prophylaxis with fluconazole (n = 191), liposomal amphotericin B (n = 105), voriconazole (n = 62), caspofungin (n = 27) and/or posaconazole (n = 22). We performed detailed reviews of patient charts and laboratory values in close cooperation with treating physicians and nursing staff and participated regularly in ward and chart rounds. Potential drug interactions were assessed using the electronic database Micromedex® 1.0 (Healthcare Series). In terms of adverse drug events, caspofungin (56%) and voriconazole (58%) revealed a slightly more favourable safety profile than liposomal amphotericin B (66%) and posaconazole (64%). We confirmed frequent nephrotoxic effects with the use of liposomal amphotericin B (20%). Regarding potential drug interactions, 97 (66%) of 147 evaluated patients were exposed to at least 1 of 22 different potentially interacting drug combinations involving systemic antifungal agents. Cyclosporine was the most prevalent potentially interacting drug in our cohort. Systemic antifungal drugs are widely used in the haematology/oncology setting and exhibit numerous potential drug interactions and adverse events in cancer patients. Our results highlight the challenges related to antifungal drugs and should valuably contribute to a safe and efficient application of this increasingly important class of drugs. Copyright © 2012 John Wiley & Sons, Ltd.

Effectiveness of two-year clopidogrel + aspirin in abolishing the risk of very late thrombosis after drug-eluting stent implantation (from the TYCOON [two-year ClOpidOgrel need] study).

PubMed

Tanzilli, Gaetano; Greco, Cesare; Pelliccia, Francesco; Pasceri, Vincenzo; Barillà, Francesco; Paravati, Vincenzo; Pannitteri, Gaetano; Gaudio, Carlo; Mangieri, Enrico

2009-11-15

It remains unclear whether dual antiplatelet therapy >12 months might carry a better prognosis after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). To address the hypothesis that in the real world the risk of very late thrombosis after PCI with DESs can be decreased by an extended use of clopidogrel, we set up the Two-Year ClOpidOgrel Need (TYCOON) registry and prospectively investigated the impact on very late thrombosis of 12- versus 24-month dual antiplatelet regimens in an unselected population. The registry enrolled 897 consecutive patients who underwent PCI with stenting from January 1, 2003, to December 31, 2004, and had dual antiplatelet therapy. All patients had a 4-year clinical follow-up. In the 447 patients with DES implantation, the dual antiplatelet regimen after PCI was given for 12 months in the 173 patients treated in 2003 (12-month group) and for 24 months in the 274 patients treated in 2004 (24-month group). Comparison between groups did not reveal any significant difference in baseline clinical characteristics, angiographic and procedural features, and major adverse cardiac events. During follow-up, there were 5 cases of stent thrombosis after PCI in the 12-month DES group and 1 case in the 24-month DES group (p = 0.02). Specifically, there were 2 cases of subacute thrombosis (1 in each group), no case of late thrombosis, and 4 cases of very late thrombosis occurring at 13, 15, 17, and 23 months after DES implantation in the 12-month group only. In conclusion, a 2-year dual antiplatelet regimen with aspirin and clopidogrel can prevent the occurrence of very late stent thrombosis after PCI with DESs.

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T exhibit additive prognostic value for the outcome of critically ill patients.

PubMed

Lenz, Max; Krychtiuk, Konstantin A; Goliasch, Georg; Distelmaier, Klaus; Wojta, Johann; Heinz, Gottfried; Speidl, Walter S

2018-04-01

Patients treated at medical intensive care units suffer from various pathologies and often present with elevated troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Both markers may reflect different forms of cardiac involvement in critical illness. Therefore, the aim of our study was to examine the synergistic prognostic potential of NT-proBNP and high-sensitivity TnT (hs)TnT in unselected critically ill patients. We included all consecutive patients admitted to our intensive care unit within one year, excluding those suffering from acute myocardial infarction or undergoing cardiac surgery and measured NT-proBNP and TnT plasma levels on the day of admission and 72 hours thereafter. Of the included 148 patients, 52% were male, mean age was of 64.2 ± 16.8 years and 30-day mortality was 33.2%. Non-survivors showed significantly higher NT-proBNP and TnT plasma levels as compared with survivors ( p<0.01). An elevation of both markers exhibited an additive effect on mortality, as those with both NT-proBNP and TnT levels above the median had a 30-day mortality rate of 51.0%, while those with both markers below the median had a 16.7% mortality rate (hazard ratio 3.7). These findings were independent of demographic and clinical parameters ( p<0.05). Our findings regarding the individual predictive properties of NT-proBNP and TnT are in line with literature. However, we were able to highlight that they exhibit additive prognostic potential which exceeds their individual value. This might be attributed to a difference in underlying pathomechanisms and an assessment of synergistic risk factors.

Prevalent involvement of thenar motor fibres in vineyard workers with carpal tunnel syndrome.

PubMed

Mondelli, M; Baldasseroni, A; Aretini, A; Ginanneschi, F; Padua, L

2010-08-01

Carpal tunnel syndrome (CTS) has a high prevalence in agricultural workers, especially those engaged in vineyards. We postulated that vineyard CTS was electrophysiologically different from CTS of other subjects. We performed a retrospective cross-sectional electrophysiological study of two cohorts of consecutive patients with CTS, the first consisting of vineyard workers and the second, of other unselected types of workers, housewives and pensioners. Thirty-three vineyard workers (mean age 46.8years, 42% women) and 205 patients with other occupations (mean age 53.7years; 66% women) were enrolled. All patients underwent sensory and motor neurography of the median and ulnar nerves. Differences in demographic and electrophysiological findings between groups were calculated and multiple linear regression analysis was performed to eliminate the influence of potential confounding factors (age, sex, BMI, clinical severity of CTS) on the results of univariate difference analysis. Univariate analysis showed that DML was longer and compound muscle action potential amplitude of the median nerve, recorded from the abductor pollicis brevis muscle, was smaller in vineyard workers than in the other CTS patients. These differences remained significant after adjusting the results for confounding factors. The vineyard workers showed a different pattern of CTS than the other patients: thenar motor fibres were more affected, presumably due to chronic compression on the thenar branch. This suggests an association between "common" CTS and thenar mononeuropathy. Occupational physiologists should clarify the mechanisms of neuromuscular engagement in particular jobs and ergonomists design suitable working tools, because many "individual" risk factors are difficult to change, but workplace-related risk factors can be modified. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The use of metabolic balance studies in the objective discrimination between intestinal insufficiency and intestinal failure.

PubMed

Prahm, August P; Brandt, Christopher F; Askov-Hansen, Carsten; Mortensen, Per B; Jeppesen, Palle B

2017-09-01

Background : In research settings that use metabolic balance studies (MBSs) of stable adult patients with short bowel syndrome, intestinal failure (IF) and dependence on parenteral support (PS) have been defined objectively as energy absorption <84% of calculated basal metabolic rate (BMR), wet weight (WW) absorption <23 g · kg body weight -1 · d -1 , or both. Objective: This study aimed to explore and validate these borderlines in the clinical setting. Design: Intestinal absorption was measured from April 2003 to March 2015 in 175 consecutive patients with intestinal insufficiency (INS) in 96-h MBSs. They had not received PS 3 mo before referral. Results: To avoid the need for PS, the minimum absorptive requirements were energy absorption of ≥81% of BMR and WW absorption of ≥21 g · kg body weight -1 · d -1 , which were equivalent to findings in research settings (differences of 3.6% and 8.7%; P = 0.65 and 0.60, respectively). Oral failure defined as energy intake <130% of calculated BMR or WW intake <40 g · kg body weight -1 · d -1 was seen in 71% and 82% of the 10% of patients with the lowest energy absorption and WW absorption, respectively. Conclusions: In clinical settings, the borderlines between INS and IF were not significantly different from those in research settings, even in an unselected patient population in which oral failure was also a predominant cause of nutritional dyshomeostasis. MBSs may be recommended to identify the individual patient in the spectrum from INS to IF, to objectivize the cause of nutritional dyshomeostasis (oral failure, malabsorption, or both), and to quantify the effects of treatment. © 2017 American Society for Nutrition.

Quality of Life Outcomes after Transcatheter Aortic Valve Replacement in an Unselected Population. A Report from the STS/ACC TVT Registry™

PubMed Central

Arnold, Suzanne V.; Spertus, John A.; Vemulapalli, Sreekanth; Li, Zhuokai; Matsouaka, Roland A.; Baron, Suzanne J.; Vora, Amit N.; Mack, Michael J.; Reynolds, Matthew R.; Rumsfeld, John S.; Cohen, David J.

2017-01-01

Importance In clinical trials, transcatheter aortic valve replacement (TAVR) has been shown to improve symptoms and quality of life. As this technology moves into general clinical practice, it is critical to evaluate the health status outcomes among unselected patients treated with TAVR. Design/Participants Observational study of patients with severe aortic stenosis treated with TAVR in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry. Main Outcomes Disease-specific health status was assessed at baseline and at 30 days (n=31,636) and 1 year after TAVR (n=7,014) with the Kansas City Cardiomyopathy Questionnaire-overall summary score (KCCQ-OS; range 0–100 points). We examined factors associated with health status at 1 year after TAVR using multivariable linear regression, with adjustment for baseline health status and accounting for clustering of patients within sites. Results Mean baseline KCCQ-OS was 42.3±23.7, indicating substantial health status impairment. Surviving patients had, on average, large improvements in health status at 30 days that persisted to 1 year, with a mean improvement in the KCCQ-OS of 27.6 points at 30 days and 31.9 points at 1 year. Worse baseline health status, older age, higher ejection fraction, lung disease, home oxygen, lower mean aortic valve gradient, prior stroke, diabetes, pacemaker, atrial fibrillation, slower gait speed, and non-femoral access were associated with worse health status at 1 year. Overall, 62.3% of patients had a favorable outcome at 1 year (alive with reasonable quality of life [KCCQ-OS ≥60] and no significant decline [≥10 points] from baseline) with the lowest rates seen among patients with severe lung disease (51.4%), on dialysis (47.7%), or with very poor baseline health status (49.2%). Conclusion In a national, contemporary clinical practice cohort of unselected patients, we found that improvement in health status following TAVR was similar to that seen in the pivotal clinical trials. While the health status results were favorable for the majority of patients, ~1 in 3 patients still had a poor outcome 1 year after TAVR. Continued efforts are needed to improve patient selection and procedural/post-procedural care in order to maximize health status outcomes of this evolving therapy. PMID:28146260

The Effects and Costs of a Group-Based Education Programme for Self-Management of Patients with Type 2 Diabetes. A Community-Based Study

ERIC Educational Resources Information Center

Molsted, Stig; Tribler, Jane; Poulsen, Peter B.; Snorgaard, Ole

2012-01-01

The worldwide epidemic of Type 2 diabetes necessitates evidence-based self-management education programmes. The purpose of this study was to investigate the effects and costs of an empowerment-based structured diabetes self-management education programme in an unselected group of patients with Type 2 diabetes. Seven hundred and two patients…

Safe refeeding management of anorexia nervosa inpatients: an evidence-based protocol.

PubMed

Hofer, Michael; Pozzi, Antonio; Joray, Maya; Ott, Rebecca; Hähni, Florence; Leuenberger, Michéle; von Känel, Roland; Stanga, Zeno

2014-05-01

Anorexia nervosa is associated with several serious medical complications related to malnutrition, severe weight loss, and low levels of micronutrients. The refeeding phase of these high-risk patients bears a further threat to health and potentially fatal complications. The objective of this study was to examine complications due to refeeding of patients with anorexia nervosa, as well as their mortality rate after the implementation of guidelines from the European Society of Clinical Nutrition and Metabolism. We analyzed retrospective, observational data of a consecutive, unselected anorexia nervosa cohort during a 5-y period. The sample consisted of 65 inpatients, 14 were admitted more than once within the study period, resulting in 86 analyzed cases. Minor complications associated with refeeding during the first 10 d (replenishing phase) were recorded in nine cases (10.5%), four with transient pretibial edemas and three with organ dysfunction. In two cases, a severe hypokalemia occurred. During the observational phase of 30 d, 16 minor complications occurred in 14 cases (16.3%). Six infectious and 10 non-infectious complications occurred. None of the patients with anorexia nervosa died within a follow-up period of 3 mo. Our data demonstrate that the seriousness and rate of complications during the replenishment phase in this high-risk population can be kept to a minimum. The findings indicate that evidence-based refeeding regimens, such as our guidelines are able to reduce complications and prevent mortality. Despite anorexia nervosa, our sample were affected by serious comorbidities, no case met the full diagnostic criteria for refeeding syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

Aortic valve calcification - a commonly observed but frequently ignored finding during CT scanning of the chest.

PubMed

Raju, Prashanth; Sallomi, David; George, Bindu; Patel, Hitesh; Patel, Nikhil; Lloyd, Guy

2012-06-01

To describe the frequency and severity of Aortic valve calcification (AVC) in an unselected cohort of patients undergoing chest CT scanning and to assess the frequency with which AVC was being reported in the radiology reports. Consecutive CT scan images of the chest and the radiological reports (December 2009 to May 2010) were reviewed at the district general hospital (DGH). AVC on CT scan was visually graded on a scale ranging from 0 to IV (0 = no calcification, IV = severe calcification). Total of 416 (232 male; 184 female) CT chest scans [Contrast enhanced 302 (72%), unenhanced 114 (28%)] were reviewed. Mean age was 70.55 ± 11.48 years. AVC in CT scans was identified in 95 of the 416 patients (22.83%). AVC classification was as follows: Grade I: 60 (63.15%), Grade II: 22 (23.15%), Grade III: 9 (9.47%), Grade IV: 4 (4.21%). Only one CT report mentioned AVC. Only 31 of 95 AVC had Transthoracic echocardiogram (TTE). The interval time between CT scan and TTE was variable.   Aortic valve calcification in CT chest scans is a common finding and studies have shown that it is strongly related to the presence and severity of aortic valve disease. As CT scans are considered as a valuable additional screening tool for detection of aortic stenosis, AVC should always be commented upon in the radiology reports. Furthermore, patients with at least Grade III and IV AVC should be sent for TTE. © 2012 Blackwell Publishing Ltd.

Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?

PubMed

Otten, Henny G; Brummelhuis, Walter J; Fritsch-Stork, Ruth; Leavis, Helen L; Wisse, Bram W; van Laar, Jacob M; Derksen, Ronald H W M

2017-01-01

The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients. In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes). Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation. We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

High-Frequency Oscillations and Seizure Generation in Neocortical Epilepsy

ERIC Educational Resources Information Center

Worrell, Greg A.; Parish, Landi; Cranstoun, Stephen D.; Jonas, Rachel; Baltuch, Gordon; Litt, Brian

2004-01-01

Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60--100 Hz) epileptiform oscillations…

Mutation Analysis of IDH1/2 Genes in Unselected De novo Acute Myeloid Leukaemia Patients in India - Identification of A Novel IDH2 Mutation.

PubMed

Raveendran, Sureshkumar; Sarojam, Santhi; Vijay, Sangeetha; Geetha, Aswathy Chandran; Sreedharan, Jayadevan; Narayanan, Geetha; Sreedharan, Hariharan

2015-01-01

IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2 c.515_516GG>AA mutation, all the other identified mutations were reported mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA mutation replaces 172nd arginine to lysine in the active site of the enzyme. Even though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed significant higher platelet count and NPM1 mutations. IDH2 mutated patients displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations in the IDH1/2 mutated cases showed type A mutation. The present data suggest that IDH1/2 mutations are associated with normal cytogenetics and type A NPM1 mutations in adult Indian AML patients.

Therapeutic effect of immunoadsorption and subsequent immunoglobulin substitution in patients with dilated cardiomyopathy: Results from the observational prospective Bad Berka Registry.

PubMed

Ohlow, Marc-Alexander; Brunelli, Michele; Schreiber, Matthias; Lauer, Bernward

2017-02-01

Elimination of cardiac autoantibodies, frequently detected in patients with dilated cardiomyopathy (DCM), with immunoadsorption (IA) improves functional capacity and left ventricular (LV) function. This study aimed to prospectively address this issue in a large cohort of unselected patients. Consecutive patients undergoing IA followed by IgG substitution were included. Clinical and echocardiographic parameters were assessed at baseline (BL) and 12-month follow-up (FU). Patients were classified as IA responders when ≥2 of the following criteria were achieved: improvement in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) ≥5 points, symptoms [≥1 New York Heart Association (NYHA) class], LV ejection fraction (EF) ≥10% or decrease in LV end-diastolic diameter (EDD) ≥10%, or N-terminal pro B-type natriuretic peptide (NT-pro-BNP) ≥50%. 93 patients (median age 61 years, LVEF 30%, duration of symptoms 14 months, 87% in NYHA class III/IV, >90% treated with β-blocker/angiotensin-converting enzyme inhibitor) were included. When the entire cohort was analyzed, a significant improvement in MLHFQ (50 vs. 26 points), NYHA-class (median 3.0 vs. 2.0), LVEF (30% vs. 38%), LVEDD (62 vs. 59mm), NT-pro-BNP (892 vs. 523pg/ml) was observed at FU (p<0.05 for all). 48% (n=43) were classified as responders. Those were characterized by a shorter disease duration (11 vs. 22 months), larger BL LVEDD (64 vs. 60mm), presence of >1 viral genome, and higher values of mononuclear inflammatory cells at endomyocardial biopsy. Sixteen (17.2%) patients experienced IA related complications. A positive response is observed in 48% of inflammatory DCM patients undergoing IA, and this translates into a significant improvement in clinical and echocardiographic parameters. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Non-optic glioma in adults and children with neurofibromatosis 1.

PubMed

Sellmer, Laura; Farschtschi, Said; Marangoni, Marco; Heran, Manraj K S; Birch, Patricia; Wenzel, Ralph; Friedman, Jan M; Mautner, Victor-Felix

2017-02-15

Non-optic gliomas occur in 5% of children with NF1, but little is known about these tumours in adults. We aimed to investigate progression, spontaneous regression and the natural history of non-optic gliomas in adults and compare these findings to the results found in children. One thousand seven hundred twenty-two brain MRI scans of 562 unselected individuals with NF1 were collected at the NF outpatient department of the University Hospital Hamburg-Eppendorf between 2003 and 2015. The number of scans per patient ranged from one to 12; patients were followed for a median of 3.7 years. We identified 24 patients (4.3%) with non-optic gliomas. Median age at first scan with glioma was 21.2 years, much higher than in previous publications. Only seven of the 24 non-optic glioma patients were symptomatic. Five of 24 patients had multiple non-optic gliomas. Four individuals developed a new tumour, and 4 cases showed progression. The risk of new tumour development was 0.19% (95% confidence interval 0.06% to 0.52%) per patient year of follow-up for patients over 10 years. The rate of progressing non-optic gliomas per patient year of follow-up in the first 5 years after tumour diagnosis was 4.7% (95% confidence interval 1.5% to 12%). Non-optic gliomas are twice as common in an unselected cohort of NF1 patients as previously reported. This is likely due to increased frequency of diagnosis of asymptomatic tumours when routine MRIs are performed and a higher prevalence in older individuals.

Nature and prognostic importance of abnormal glucose tolerance and diabetes in acute heart failure.

PubMed

Berry, C; Brett, M; Stevenson, K; McMurray, J J V; Norrie, J

2008-03-01

To investigate the nature and importance of blood glucose abnormalities in an unselected heart failure (HF) population. Cohort study. Urban University hospital. All index emergency HF admissions to one University hospital during the year 2000 were studied. 454 consecutive index admissions had blood chemistry, diabetic status and follow-up information recorded. 390 (86%) patients had an echocardiogram, of whom 117 (30%) had preserved left ventricular systolic function and 110 (24%) had diabetes. Sixty (13%) patients had abnormal glucose tolerance (8.0-10.99 mmol/l), and 284 (63%) patients had a normal admission blood glucose (<8 mmol/l). 51 (11.2%) patients died in hospital. After adjustment for other prognostic attributes, abnormal glucose tolerance (Cox hazard ratio HR, 95% CI: 5.920, 1.03 to 34.00; p = 0.046) but not diabetes (HR 3.46, 0.75 to 16.02; p = 0.112) predicted in-hospital mortality. During follow-up (median 812 (range 632-978) days), 104 (36.6%), 30 (50.0%) and 55 (50%) patients with a normal admission blood glucose concentration, abnormal glucose tolerance and diabetes, respectively, died (log rank test p = 0.0037, adjusted p = 0.075). Compared with patients with normal admission blood glucose, abnormal glucose tolerance (adjusted HR: 1.41 (0.92 to 2.16); p = 0.12) and diabetes (adjusted HR: 2.02 (1.41 to 2.88); p = 0.0001) predicted mortality. Considering glucose on admission as a continuous covariate, a 2 mmol/l increase was associated with a HR of 1.08 (1.03 to 1.13), p = 0.0010, which after adjustment for the above covariates became 1.08 (1.03 to 1.13), p = 0.0023. Admission blood glucose concentration and diabetes are prognostically important in HF and could help target some patients for more intensive therapy.

Single-site Laparoscopic Colorectal Surgery Provides Similar Clinical Outcomes Compared to Standard Laparoscopic Surgery: An Analysis of 626 Patients

PubMed Central

Sangster, William; Messaris, Evangelos; Berg, Arthur S.; Stewart, David B.

2015-01-01

BACKGROUND Compared to standard laparoscopy, single-site laparoscopic colorectal surgerymay potentially offer advantages by creating fewer surgical incisions and providing a multi-functional trocar. Previous comparisons, however, have been limited by small sample sizes and selection bias. OBJECTIVE To compare 60-day outcomes between standard laparoscopic and single-site laparoscopic colorectal surgery patients undergoing elective and urgent surgeries. DESIGN This was an unselected retrospective cohort study comparing patients who underwent elective and unplanned standard laparoscopic or single-site laparoscopic colorectal resections for benign and malignant disease between 2008 and 2014. Outcomes were compared using univariate analyses. SETTING This study was conducted at a single institution. PATIENTS A total of 626 consecutive patients undergoing laparoscopic colorectal surgery were included. MAIN OUTCOME MEASURES Morbidity and mortality within 60 postoperative days. RESULTS 318 (51%) and 308 (49%) patients underwent standard laparoscopic and single-site laparoscopic procedures, respectively. No significant difference was noted in mean operative time (Standard laparoscopy 182.1 ± 81.3 vs. Single-site laparoscopy 177±86.5, p=0.30) and postoperative length of stay (Standard laparoscopy 4.8±3.4 vs. Single-site laparoscopy 5.5 ± 6.9, p=0.14). Conversions to laparotomy and 60-day readmissions were also similar for both cohorts across all procedures performed. A significant difference was identified in the number of patients who developed postoperative complications (Standard laparoscopy 19.2% vs. Single-site laparoscopy 10.7%, p=0.004), especially with respect to surgical-site infections (Standard laparoscopy 11.3% vs. Single-site laparoscopy 5.8%, p=0.02). LIMITATIONS This was a retrospective, single institution study. CONCLUSIONS Single-site laparoscopic colorectal surgery demonstrates similar results to standard laparoscopic colorectal surgery in regards to operative time, length of stay and readmissions. Single-site laparoscopic colorectal surgery may provide advantages in limiting the development of certain complications such as superficial surgical-site infections. PMID:26252848

Can intractable discogenic back pain be managed by low-level laser therapy without recourse to operative intervention?

PubMed Central

Ip, David; Fu, Nga-Yue

2015-01-01

Objective The aim of the study reported here was to investigate the possible clinical role of low-level laser therapy (LLLT) in discogenic back pain patients who failed to respond to a conventional physical therapy program to avoid recourse to operative intervention. Methods The paper reports on the long-term mean 5-year prospective follow-up of a patient cohort of 50 unselected patients visiting our tertiary referral pain center for discogenic back pain who had had a single-level lesion documented by magnetic resonance imaging followed by subsequent discography to confirm the affected disc being the pain generator. All of the patients who entered the study had failed response to a combination of nonsteroidal anti-inflammatory agents and had had not less than 3 months of conventional physical therapy. LLLT, at a wavelength of 810 nm wavelength emitted from a GaAIAs semiconductor laser device with 5.4 J per point and a power density of 20 mW/cm2, was employed. The treatment regimen consisted of three sessions of treatment per week for 12 consecutive weeks. Results All but one patient had significant improvement in their Oswestry Disability Index score, from a mean of 50% score to a mean of 10% score, at the end of treatment at 12 weeks. In addition, surprisingly, the improvement was found maintained at follow-up assessments 1 year and 5 years later. The one patient among the 50 patients who failed to respond eventually required surgery, while the others did not require surgery. Conclusion We conclude that LLLT is a viable option in the conservative treatment of discogenic back pain, with a positive clinical result of more than 90% efficacy, not only in the short-term but also in the long-term, with lasting benefits. PMID:26064065

Intrinsic Limitations to Unilateral Parathyroid Exploration

PubMed Central

Moore, Francis D.; Mannting, Finn; Tanasijevic, Milenko

1999-01-01

Objective To evaluate a method of limited parathyroid exploration for primary hyperparathyroidism. Summary Background Data Although preoperative localization of parathyroid adenomas has become sensitive enough for clinical practice, it has not achieved success as the basis for limited parathyroid exploration, because multiglandular disease is routinely underdiagnosed. The rapid intraoperative parathyroid hormone assay is sensitive for multiglandular disease, because hormone levels will not fall within 10 minutes of adenoma removal if additional abnormal tissue is present. A combination technique in which the exploration is limited according to the localization studies and the success is confirmed with the parathyroid hormone assay has promise for producing a high rate of curative limited parathyroid explorations. Methods Forty-eight consecutive patients with primary hyperparathyroidism and indications for surgery underwent preoperative localization. After tests, 45 patients underwent unilateral parathyroid exploration and confirmation of the success of unilateral exploration during surgery using the rapid parathyroid hormone assay. The intraoperative management of these patients and their follow-up to 3 months was recorded. Results Thirty-two of the 48 patients (67%) had successful unilateral exploration as gauged by a marked drop in parathyroid hormone levels during the procedure and by 3-month clinical follow-up. Of the 16 patients who ultimately underwent bilateral exploration, 7 had parathyroid hormone levels that did not fall after adenoma removal. Of these seven, five were found to have a second adenoma and two had slow metabolism of hormone with no additional abnormal tissue found. In 5 of the 16 patients, bilateral exploration was performed for erroneous localization. Four additional patients underwent bilateral exploration for improved exposure or negative results on localization tests. Conclusions These results show that unilateral parathyroid exploration is limited by the intrinsic 15% rate of multiglandular primary hyperparathyroidism, combined with the imperfections of preoperative localizing techniques. Although an 85% rate of unilateral exploration can theoretically be obtained for unselected cases, the other vagaries of the technique make a 70% rate a more reasonable expectation. PMID:10493485

Lack of nephrotoxicity of gadodiamide in unselected hospitalized patients.

PubMed

Trivedi, Hariprasad; Raman, Lakshmi; Benjamin, Heather; Batwara, Ruchika

2009-09-01

The nephrotoxicity of gadolinium-based magnetic resonance contrast media has not been adequately studied. We evaluated the nephrotoxicity of gadolinium-based contrast media in hospitalized patients who underwent magnetic resonance imaging (MRI) as part of routine clinical care. Subjects who had a serum creatinine measurement during the 7 days before MRI and at least 1 other measurement 2 to 3 days after MRI were included. Patients who underwent noncontrasted MRI served as controls. There were 162 subjects (mean age, 57.8 +/- 16.9 years; 91 men and 71 women) and 125 controls (mean age, 64.6 +/- 18 years; 62 men and 63 women). All contrast-enhanced MRI studies utilized gadodiamide (Omniscan; GE Healthcare, Waukesha, WI). Subjects who received gadodiamide showed no difference in the incidence of acute renal insufficiency compared with controls (increase in serum creatinine >or= 25%, 11.1% vs 12.9%, respectively; P = 0.6; increase in serum creatinine by 0.5 mg/dL, 5.6% vs 3.2%, respectively; P = 0.4). There was no significant increase in serum creatinine baseline versus 48 hours in either the subjects who received gadodiamide (0.95 +/- 0.58 vs 0.96 +/- 0.65 mg/dL; P = 0.7) or controls (0.96 +/- 0.65 vs 0.88 +/- 0.43 mg/dL; P = 0.7). Our findings showed a lack of significant nephrotoxicity of gadodiamide in unselected hospitalized patients.

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

PubMed Central

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-01-01

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing. PMID:29348823

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

PubMed

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-12-22

Pathogenic germline BRCA1 , BRCA2 ( BRCA1/2 ), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1 ), 8 (3.5%; BRCA2 ), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D ), 2 (0.9%; ATM ), 1 (0.4%; MRE11A ), 1 ( FANCC ), and 1 ( GABRA6 ). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2 . Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

Rome Foundation-Asian working team report: Asian functional gastrointestinal disorder symptom clusters.

PubMed

Siah, Kewin Tien Ho; Gong, Xiaorong; Yang, Xi Jessie; Whitehead, William E; Chen, Minhu; Hou, Xiaohua; Pratap, Nitesh; Ghoshal, Uday C; Syam, Ari F; Abdullah, Murdani; Choi, Myung-Gyu; Bak, Young-Tae; Lu, Ching-Liang; Gonlachanvit, Sutep; Boon, Chua Seng; Fang, Fan; Cheong, Pui Kuan; Wu, Justin C Y; Gwee, Kok-Ann

2018-06-01

Functional gastrointestinal disorders (FGIDs) are diagnosed by the presence of a characteristic set of symptoms. However, the current criteria-based diagnostic approach is to some extent subjective and largely derived from observations in English-speaking Western patients. We aimed to identify latent symptom clusters in Asian patients with FGID. 1805 consecutive unselected patients with FGID who presented for primary or secondary care to 11 centres across Asia completed a cultural and linguistic adaptation of the Rome III Diagnostic Questionnaire that was translated to the local languages. Principal components factor analysis with varimax rotation was used to identify symptom clusters. Nine symptom clusters were identified, consisting of two oesophageal factors (F6: globus, odynophagia and dysphagia; F9: chest pain and heartburn), two gastroduodenal factors (F5: bloating, fullness, belching and flatulence; F8 regurgitation, nausea and vomiting), three bowel factors (F2: abdominal pain and diarrhoea; F3: meal-related bowel symptoms; F7: upper abdominal pain and constipation) and two anorectal factors (F1: anorectal pain and constipation; F4: diarrhoea, urgency and incontinence). We found that the broad categorisation used both in clinical practice and in the Rome system, that is, broad anatomical divisions, and certain diagnoses with long historical records, that is, IBS with diarrhoea, and chronic constipation, are still valid in our Asian societies. In addition, we found a bowel symptom cluster with meal trigger and a gas cluster that suggests a different emphasis in our populations. Future studies to compare a non-Asian cohort and to match to putative pathophysiology will help to verify our findings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Measurement Properties of the Persian Translated Version of Graves Orbitopathy Quality of Life Questionnaire: A Validation Study.

PubMed

Kashkouli, Mohsen Bahmani; Karimi, Nasser; Aghamirsalim, Mohamadreza; Abtahi, Mohammad Bagher; Nojomi, Marzieh; Shahrad-Bejestani, Hadi; Salehi, Masoud

2017-02-01

To determine the measurement properties of the Persian language version of the Graves orbitopathy quality of life questionnaire (GO-QOL). Following a systematic translation and cultural adaptation process, 141 consecutive unselected thyroid eye disease (TED) patients answered the Persian GO-QOL and underwent complete ophthalmic examination. The questionnaire was again completed by 60 patients on the second visit, 2-4 weeks later. Construct validity (cross-cultural validity, structural validity and hypotheses testing), reliability (internal consistency and test-retest reliability), and floor and ceiling effects of the Persian version of the GO-QOL were evaluated. Furthermore, Rasch analysis was used to assess its psychometric properties. Cross-cultural validity was established by back-translation techniques, committee review and pretesting techniques. Bi-dimensionality of the questionnaire was confirmed by factor analysis. Construct validity was also supported through confirmation of 6 out of 8 predefined hypotheses. Cronbach's α and intraclass correlation coefficient (ICC) were 0.650 and 0.859 for visual functioning and 0.875 and 0.896 for appearance subscale, respectively. Mean quality of life (QOL) scores for visual functioning and appearance were 78.18 (standard deviation, SD, 21.57) and 56.25 (SD 26.87), respectively. Person reliabilities from the Rasch rating scale model for both visual functioning and appearance revealed an acceptable internal consistency for the Persian GO-QOL. The Persian GO-QOL questionnaire is a valid and reliable tool with good psychometric properties in evaluation of Persian-speaking patients with TED. Applying Rasch analysis to future versions of the GO-QOL is recommended in order to perform tests for linearity between the estimated item measures in different versions.

Nocturnal hypoventilation in neuromuscular disease: prevalence according to different definitions issued from the literature.

PubMed

Ogna, Adam; Quera Salva, Maria-Antonia; Prigent, Helene; Mroue, Ghassane; Vaugier, Isabelle; Annane, Djillali; Lofaso, Frederic; Orlikowski, David

2016-05-01

Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscular diseases (NMD). Home mechanical ventilation (HMV) is used to treat hypoventilation, identified by daytime hypercapnia or nocturnal desaturation. Recently, transcutaneous measure of CO2 (TcCO2) has been increasingly used to detect hypoventilation, using different cut-offs. We aimed to compare the prevalence of hypoventilation in an unselected adult NMD population according to different definitions issued from the literature. All consecutive nocturnal capno-oximetries performed between 2010 and 2014 in unventilated adult NMD patients were analysed retrospectively. Concomitant blood gas analysis and lung function data were collected. Patients on oxygen therapy were excluded. Hypoventilation was defined according to eight criteria, based on daytime PaCO2, daytime base excess, nocturnal SpO2 or TcCO2. Data from 232 patients were analysed (mean age 43.1 ± 15.4 years; 50.0 % women; vital capacity 59.2 ± 24.2 % of predicted). The hypoventilation prevalence was 10.3 to 61.2 %, depending on the used definition. The different definitions showed 49.1 to 94.8 % concordance (Cohen's kappa for agreement 0.115 to 0.763). Overall agreement between the eight definitions was poor (Light's kappa 0.267), and agreement between definitions based on nocturnal SpO2 and those based on TcCO2 was even lower (Light's kappa 0.204). We found large differences in hypoventilation prevalence according to the used definition. This has practical consequences, as HMV indication relies upon hypoventilation detection. We believe that capno-oximetry should be included in the diagnostic tools used to detect hypoventilation but this requires an update of consensus guidelines to agree upon the best definition.

Two-year follow-up of low-level laser therapy for elderly with painful adhesive capsulitis of the shoulder

PubMed Central

Ip, David; Fu, Nga-Yue

2015-01-01

Introduction This paper reports on the medium-term mean 2-year prospective follow-up of a patient cohort of 35 unselected elderly patients with mean age of 65 years who visited our tertiary referral pain center for painful adhesive capsulitis of the shoulder managed with low-level laser therapy (LLLT). Materials and methods All patients in this prospective cohort study had documentation of the diagnosis by contrast-enhanced magnetic resonance imaging before study entry and all had failed to respond to a combination of conventional physical therapy and nonsteroidal anti-inflammatory medications for not fewer than 4 weeks. LLLT, at a wavelength of 810 nm emitted from a GaAIAs semiconductor laser device with 5.4 J per point and a power density of 20 mW/cm2, was employed to irradiate six predetermined anatomic points and two acupuncture points. The treatment regimen consisted of three sessions of treatment per week for 8 consecutive weeks. Each treatment session lasted 180 seconds. Serial clinical assessment was undertaken using the Constant–Murley shoulder score. Results A total of 50 painful shoulder joints were treated, as a number of elderly presented with bilateral symptoms. All but four painful shoulders showed significant improvement in Constant–Murley shoulder score at the end of 8-weeks’ LLLT treatment and, surprisingly, the improvement was found maintained at follow-up assessments at 1 year and 2 years. Conclusion We conclude that LLLT is a viable option in the conservative treatment of shoulder pain arising from adhesive capsulitis of the shoulder in the elderly, with a positive clinical result of more than 90% and with clinical efficacy both in the short-term and the medium-term. PMID:26045677

Clinicopathologic implications of DNA mismatch repair status in endometrial carcinomas.

PubMed

Shikama, Ayumi; Minaguchi, Takeo; Matsumoto, Koji; Akiyama-Abe, Azusa; Nakamura, Yuko; Michikami, Hiroo; Nakao, Sari; Sakurai, Manabu; Ochi, Hiroyuki; Onuki, Mamiko; Satoh, Toyomi; Oki, Akinori; Yoshikawa, Hiroyuki

2016-02-01

Endometrial carcinoma is the most common malignancy in women with Lynch syndrome caused by mismatch repair (MMR) deficiency. We investigated the clinicopathologic significance of deficient MMR and Lynch syndrome presumed by MMR analyses in unselected endometrial carcinomas. We analyzed immunohistochemistry of MMR proteins (MLH1/MSH2/MSH6/PMS2) and MLH1 promoter methylation in primary endometrial carcinomas from 221 consecutive patients. Based on these results, tumors were categorized as sporadic or probable Lynch syndrome (PLS). Clinicopathologic variables and prognosis were compared according to MMR status and sporadic/PLS classification. Deficient MMR showed only trends towards favorable overall survival (OS) compared with intact MMR (p=0.13), whereas PLS showed significantly better OS than sporadic (p=0.038). Sporadic was significantly associated with older age, obesity, deep myometrial invasion, and advanced stage (p=0.008, 0.01, 0.02 and 0.03), while PLS was significantly associated with early stage and Lynch syndrome-associated multiple cancer (p=0.04 and 0.001). The trend towards favorable OS of PLS was stronger in advanced stage than in early stage (hazard ratio, 0.044 [95% CI 0-25.6] vs. 0.49 [0.063-3.8]). In the subset receiving adjuvant therapies, PLS showed trends towards favorable disease-free survival compared to sporadic by contrast with patients receiving no adjuvant therapies showing no such trend (hazard ratio, 0.045 [95% CI 0-20.3] vs. 0.81 [0.095-7.0]). The current findings suggest that analyzing MMR status and searching for Lynch syndrome may identify a subset of patients with favorable survival and high sensitivity to adjuvant therapies, providing novel and useful implications for formulating the precision medicine in endometrial carcinoma. Copyright © 2015 Elsevier Inc. All rights reserved.

The clonal distribution and diversity of extraintestinal Escherichia coli isolates vary according to patient characteristics.

PubMed

Banerjee, Ritu; Johnston, Brian; Lohse, Christine; Chattopadhyay, Sujay; Tchesnokova, Veronika; Sokurenko, Evgeni V; Johnson, James R

2013-12-01

The clonal distribution of Escherichia coli across an unselected population in the current era of widespread antimicrobial resistance is incompletely defined. In this study, we used a newly described clonal typing strategy based on sequencing of fumC and fimH (i.e., CH typing) to infer multilocus sequence types (STs) for 299 consecutive, nonduplicate extraintestinal E. coli isolates from all cultures submitted to Olmsted County, MN, laboratories in February and March 2011 and then compared STs with epidemiological data. Forty-seven different STs were identified, most commonly ST131 (27%), ST95 (11%), ST73 (8%), ST127 (6%), and ST69 (5%). Isolates from these five STs comprised two-thirds of health care-associated (HA) isolates but only half of community-associated (CA) isolates. ST131 was represented overwhelmingly (88%) by a single recently expanded H30 subclone, which was the most extensively antimicrobial-resistant subclone overall and was especially predominant in HA infections and among adults >50 years old. In contrast, among patients 11 to 50 years old, ST69, -95, and -73 were more common. Because of the preponderance of the H30 subclone of ST131, ST diversity was lower among HA than CA isolates, and among antimicrobial-resistant than antimicrobial-susceptible isolates, which otherwise had similar ST distributions. In conclusion, in this U.S. Midwest region, the distribution and diversity of STs among extraintestinal E. coli clinical isolates vary by patient age, type of infection, and resistance phenotype. ST131 predominates among young children and the elderly, HA infections, and antimicrobial-resistant isolates, whereas other well-known pathogenic lineages are more common among adolescents and young adults, CA infections, and antimicrobial-susceptible isolates.

Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.

PubMed

Lowery, Maeve A; Wong, Winston; Jordan, Emmet J; Lee, Jonathan W; Kemel, Yelena; Vijai, Joseph; Mandelker, Diana; Zehir, Ahmet; Capanu, Marinela; Salo-Mullen, Erin; Arnold, Angela G; Yu, Kenneth H; Varghese, Anna M; Kelsen, David P; Brenner, Robin; Kaufmann, Erica; Ravichandran, Vignesh; Mukherjee, Semanti; Berger, Michael F; Hyman, David M; Klimstra, David S; Abou-Alfa, Ghassan K; Tjan, Catherine; Covington, Christina; Maynard, Hannah; Allen, Peter J; Askan, Gokce; Leach, Steven D; Iacobuzio-Donahue, Christine A; Robson, Mark E; Offit, Kenneth; Stadler, Zsofia K; O'Reilly, Eileen M

2018-02-28

Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands : Design and rationale of the Chronic Heart failure ESC guideline-based Cardiology practice Quality project (CHECK-HF) registry.

PubMed

Brugts, J J; Linssen, G C M; Hoes, A W; Brunner-La Rocca, H P

2018-05-01

Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013-2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands. In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%. The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

Prospective assessment of the occurrence of anemia in patients with heart failure: results from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry.

PubMed

Adams, Kirkwood F; Patterson, James H; Patterson, John H; Oren, Ron M; Mehra, Mandeep R; O'Connor, Christopher M; Piña, Ileana L; Miller, Alan B; Chiong, Jun R; Dunlap, Stephanie H; Cotts, William G; Felker, Gary M; Schocken, Douglas D; Schwartz, Todd A; Ghali, Jalal K

2009-05-01

Although a potentially important pathophysiologic factor in heart failure, the prevalence and predictors of anemia have not been well studied in unselected patients with heart failure. The Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry prospectively studied the prevalence of anemia and the relationship of hemoglobin to health-related quality of life and outcomes among patients with heart failure. A random selection algorithm was used to reduce bias during enrollment of patients seen in specialty clinics or clinics of community cardiologists with experience in heart failure. In this initial report, data on prevalence and correlates of anemia were analyzed in 1,076 of the 1,082 registry patients who had clinical characteristics and hemoglobin determined by finger-stick at baseline. Overall (n = 1,082), the registry patients were 41% female and 73% white with a mean age (+/-SD) of 64 +/- 14 years (68 +/- 13 years in community and 57 +/- 14 years in specialty sites, P < .001). Among the 1,076 patients in the prevalence analysis, mean hemoglobin was 13.3 +/- 2.1 g/dL (median 13.2 g/dL); and anemia (defined by World Health Organization criteria) was present in 34%. Age identified patients at risk for anemia, with 40% of patients >70 years affected. Initial results from the STAMINA-HFP Registry suggest that anemia is a common comorbidity in unselected outpatients with heart failure. Given the strong association of anemia with adverse outcomes in heart failure, this study supports further investigation concerning the importance of anemia as a therapeutic target in this condition.

Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers.

PubMed

Vaegter, Katarina Kebbon; Lakic, Tatevik Ghukasyan; Olovsson, Matts; Berglund, Lars; Brodin, Thomas; Holte, Jan

2017-03-01

To construct a prediction model for live birth after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and single-embryo transfer (SET) after 2 days of embryo culture. Prospective observational cohort study. University-affiliated private infertility center. SET in 8,451 IVF/ICSI treatments in 5,699 unselected consecutive couples during 1999-2014. A total of 100 basal patient characteristics and treatment data were analyzed for associations with live birth after IVF/ICSI (adjusted for repeated treatments) and subsequently combined for prediction model construction. Live birth rate (LBR) and performance of live birth prediction model. Embryo score, treatment history, ovarian sensitivity index (OSI; number of oocytes/total dose of FSH administered), female age, infertility cause, endometrial thickness, and female height were all independent predictors of live birth. A prediction model (training data set; n = 5,722) based on these variables showed moderate discrimination, but predicted LBR with high accuracy in subgroups of patients, with LBR estimates ranging from <10% to >40%. Outcomes were similar in an internal validation data set (n = 2,460). Based on 100 variables prospectively recorded during a 15-year period, a model for live birth prediction after strict SET was constructed and showed excellent calibration in internal validation. For the first time, female height qualified as a predictor of live birth after IVF/ICSI. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of Microlife BP A200 Plus and Omron M6 blood pressure monitors to detect atrial fibrillation in hypertensive patients.

PubMed

Marazzi, Giuseppe; Iellamo, Ferdinando; Volterrani, Maurizio; Lombardo, Mauro; Pelliccia, Francesco; Righi, Daniela; Grieco, Fabrizia; Cacciotti, Luca; Iaia, Luigi; Caminiti, Giuseppe; Rosano, Giuseppe

2012-01-01

Self-monitoring home blood pressure (BP) devices are currently recommended for long-term follow-up of hypertension and its management. Some of these devices are integrated with algorithms aimed at detecting atrial fibrillation (AF), which is common essential hypertension. This study was designed to compare the diagnostic accuracy of two widely diffused home BP monitoring devices in detecting AF in an unselected population of outpatients referred to a hypertension clinic because of high BP. In 503 consecutive patients the authors simultaneously compared the accuracy of the Microlife(®) BP A200 Plus (Microlife) and the OMRON(®) M6 (OMRON) home BP devices, in detecting AF. Systolic and diastolic BP as well as heart rate (HR) values detected by the two devices were not significantly different. Pulse irregularity was detected in 124 and 112 patients with the OMRON M6 and Microlife BP A200 Plus devices, respectively. Simultaneous electrocardiogram (ECG) recording revealed that pulse irregularity was due to AF in 101 patients. Pulse irregularity detected by the OMRON M6 device corresponded to AF in 101, to supraventricular premature beats in 18, and to frequent premature ventricular beat in five patients, respectively. Pulse irregularity detected by the Microlife BP A200 Plus device corresponded to AF in 93, to supraventricular premature beats in 14, and to ventricular premature beats in five patients. The sensitivity for detecting AF was 100%, the specificity was 92%, and diagnostic accuracy 95% for the OMRON M6 and 100%, 92%, and 95 for the Microlife BP A200 Plus, respectively. AF was newly diagnosed by ECG recordings in 47 patients, and was detected in all patients by the OMRON device, and in 42 patients by the Microlife device. These results indicate that OMRON M6 is more accurate than Microlife BP A200 Plus in detecting AF in patients with essential hypertension. Widespread use of these devices in hypertensive patients could be of clinical benefit for the early diagnosis and treatment of this arrhythmia and related consequences.

Perfectionism and Polysomnography-Determined Markers of Poor Sleep

PubMed Central

Johann, Anna F.; Hertenstein, Elisabeth; Kyle, Simon D.; Baglioni, Chiara; Feige, Bernd; Nissen, Christoph; Riemann, Dieter; Spiegelhalder, Kai

2017-01-01

Study Objectives: Perfectionism has been suggested to represent a predisposing factor for poor sleep. However, previous studies have relied on self-reported measures. The association between perfectionism and poor sleep measured by polysomnography (PSG) warrants further investigation. Methods: The current retrospective exploratory study used the Frost Multidimensional Perfectionism Scale and PSG in an unselected sample of 334 consecutive sleep laboratory patients (140 males, 194 females, 44.6 ± 15.9 years). Data were analyzed using linear regression analyses. Results: High levels of perfectionism were associated with PSG-determined markers of poor sleep in the first sleep laboratory night. The total Frost Multidimensional Perfectionism Scale score was significantly associated with the number of nocturnal awakenings in the first sleep laboratory night. The subscales “concern over mistakes” and “personal standards” of perfectionism were significantly associated with markers of poor sleep. In contrast, there were only a few associations between perfectionism and PSG variables of the second sleep laboratory night. Conclusions: This pattern of results suggests that high levels of perfectionism may predispose individuals to sleep disturbances in the context of acute stressors. Thus, the influence of perfectionism on poor sleep should be further investigated to improve treatment. Citation: Johann AF, Hertenstein E, Kyle SD, Baglioni C, Feige B, Nissen C, Riemann D, Spiegelhalder K. Perfectionism and polysomnography-determined markers of poor sleep. J Clin Sleep Med. 2017;13(11):1319–1326. PMID:28992830

Exploiting Molecular and Immune Biology of Gastric and Gastroesophageal Adenocarcinomas to Discover Novel Therapeutic Targets.

PubMed

Elimova, Elena; Song, Shumei; Shimodaira, Yusuke; Lin, Quan; Ajani, Jaffer A

2016-11-01

Gastroesophageal carcinomas (GACs) are a significant problem worldwide, and despite many attempts to improve the outcomes of patients with these tumors, little progress has been made over the last several decades. In the past decade, only transtuzumab and ramucirumab, two drugs with marginal clinical benefit, have been approved for the treatment of patients with GACs. After second-line therapy, most treatment options are generally ineffective. Prior studies in this disease have been largely empiric, using unselected patient populations. More recently, detailed somatic genotyping, enrichment of patients based on biomarkers, and pharmacokinetic studies have opened new avenues for developing treatment options in patients with GAC.

Outcomes for patients with congenital hepatoblastoma.

PubMed

Trobaugh-Lotrario, Angela D; Chaiyachati, Barbara H; Meyers, Rebecka L; Häberle, Beate; Tomlinson, Gail E; Katzenstein, Howard M; Malogolowkin, Marcio H; von Schweinitz, Dietrich; Krailo, Mark; Feusner, James H

2013-11-01

Congenital hepatoblastoma, diagnosed in the first month of life, has been reported to have a poor prognosis; however, a comprehensive evaluation of this entity is lacking. We retrospectively reviewed two patients from the senior authors' personal series and 25 cases identified in the databases of several multicenter group studies (INT-0098, P9645, 881, P9346, HB 89, HB94, and HB 99). We compared this series with cases of congenital hepatoblastoma previously published in the literature. The 3-year survival in our case series was 86% (18/21) with a follow-up of 44-230 months (median 85.5 months). Presentation and treatment were not substantially different from hepatoblastoma cohorts unselected for age. Survival was comparable to the reported disease free survival for a similar cohort of hepatoblastoma patients unselected for age between 1986 and 2002 (82.5%) [von Schweinitz et al., Eur J Cancer 1997; 33:1243-1249]. The 2-year survival of cases reported in the literature was 0% (0/9) and 42% (10/24) for patients reported before and after 1990, respectively. Congenital hepatoblastoma does not appear to confer a worse prognosis. The improved survival of our current series of patients, collected from the past 20 years of German and American multicenter trials and personal series, suggests that the outcome of hepatoblastoma at this young age is much better than has been historically reported. More rigorous analysis should be conducted in future multicenter trials. It is possible that congenital hepatoblastoma should be treated like all other patients with hepatoblastoma provided that the child is stable enough to proceed with surgery and chemotherapy. Copyright © 2013 Wiley Periodicals, Inc.

Treatment, Outcome and Prognostic Factors in Renal Cell Carcinoma - A Single Center Study (2000-2010)

PubMed Central

Achermann, Christof; Stenner, Frank; Rothschild, Sacha I.

2016-01-01

In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitors (TKI) and mTOR inhibitors (mTORi), have a largely better outcome than those who have less exposure to these agents. The value of the prognostic scores developed by Motzer and Heng is fully reflected by the outcomes according to prognostic risk groups in our unselected patient cohort. Also, the use of surgical intervention appears to be an important prognostic factor, however with a somehow diminished effect by novel systemic therapies. The importance of multiple lines of targeted therapies is underlined by this retrospective analysis. For patients with metastatic RCC not receiving targeted therapy the median OS was 22.6 months compared to those with one TKI 25.4 months. Patients receiving a second-line therapy (median overall survival 27.6 months) and those patients with three or more lines of therapy (43.8 months) have the greatest benefit. Also, exposure to a mTORi improves survival versus non-exposure to mTORi (63.3 vs. 22.3 months, p=0.038). In conclusion a trend towards improved survival is confirmed for an unselected population when the full variety of therapeutic options is available and can be used for the individual patient. PMID:27313782

Differences in patient selection and outcomes between SilverHawk atherectomy and laser ablation in the treatment of femoropopliteal in-stent restenosis: a retrospective analysis from a single center.

PubMed

Shammas, Nicolas W; Shammas, Gail A; Jerin, Michael

2013-12-01

To analyze differences in the application and outcomes of SilverHawk atherectomy (SH) and excimer laser ablation (ELA) in the treatment of femoropopliteal in-stent restenosis (ISR) in an unselected cohort of patients treated at a single center. Between January 2005 and June 2010, 81 consecutive patients (46 men; mean age 69.1 years, range 43-86) underwent directional atherectomy (41 SH, 40 ELA) for femoropopliteal ISR lesions. Data were reviewed retrospectively on procedural outcomes, major adverse events, and 1-year target lesion revascularization (TLR) obtained from medical records and supplemented with telephone calls. The primary endpoint was symptom-driven TLR at 1 year; secondary endpoints were death and amputation. ELA was utilized more frequently than SH in longer lesions (210.4±104 vs. 126.2±79.3 mm, respectively; p=0.001), subacute presentation (55% vs. 14.6%, p=0.001), TASC D lesions (47.5% vs. 12.2%), and in patients with more angiographic thrombus (42.5% vs. 4.9%, p=0.001). Final angiographic success (<30% residual narrowing post final treatment) was similar between ELA and SH (92.5% vs. 100%, respectively, p=0.12). Bailout stenting was significantly higher with ELA vs. SH (50.0% vs. 24.4%, p=0.022). At 1 year, TLR had occurred in 48.7% of the ELA patients vs. 31.7% of the SH cases (p=0.171). Regression analysis confirmed that SH was a predictor of TLR at 1 year (hazard ratio 2.679, 95% CI 1.015 to 7.073, p=0.047). Both SH and ELA continue to have a high TLR rate in treating ISR of the femoral and popliteal arteries. A higher rate of delayed failure is seen with SH and an earlier, steeper loss of TLR-free survival is seen with ELA.

Economic impact of simplified de Gramont regimen in first-line therapy in metastatic colorectal cancer.

PubMed

Limat, Samuel; Bracco-Nolin, Claire-Hélène; Legat-Fagnoni, Christine; Chaigneau, Loic; Stein, Ulrich; Huchet, Bernard; Pivot, Xavier; Woronoff-Lemsi, Marie-Christine

2006-06-01

The cost of chemotherapy has dramatically increased in advanced colorectal cancer patients, and the schedule of fluorouracil administration appears to be a determining factor. This retrospective study compared direct medical costs related to two different de Gramont schedules (standard vs. simplified) given in first-line chemotherapy with oxaliplatin or irinotecan. This cost-minimization analysis was performed from the French Health System perspective. Consecutive unselected patients treated in first-line therapy by LV5FU2 de Gramont with oxaliplatin (Folfox regimen) or with irinotecan (Folfiri regimen) were enrolled. Hospital and outpatient resources related to chemotherapy and adverse events were collected from 1999 to 2004 in 87 patients. Overall cost was reduced in the simplified regimen. The major factor which explained cost saving was the lower need for admissions for chemotherapy. Amount of cost saving depended on the method for assessing hospital stay. In patients treated by the Folfox regimen the per diem and DRG methods found cost savings of Euro 1,997 and Euro 5,982 according to studied schedules; in patients treated by Folfiri regimen cost savings of Euro 4,773 and Euro 7,274 were observed, respectively. In addition, travel costs were also reduced by simplified regimens. The robustness of our results was showed by one-way sensitivity analyses. These findings demonstrate that the simplified de Gramont schedule reduces costs of current first-line chemotherapy in advanced colorectal cancer. Interestingly, our study showed several differences in costs between two costing approaches of hospital stay: average per diem and DRG costs. These results suggested that standard regimen may be considered a profitable strategy from the hospital perspective. The opposition between health system perspective and hospital perspective is worth examining and may affect daily practices. In conclusion, our study shows that the simplified de Gramont schedule in combination with oxaliplatin or irinotecan is an attractive option from the French Health System perspective. This safe and less costly regimen must compared to alternative options such as oral fluoropyrimidines.

Exercise duration and peak systolic blood pressure are predictive of mortality in ambulatory patients with mild-moderate chronic heart failure.

PubMed

Williams, Simon G; Jackson, Mark; Ng, Leong L; Barker, Diane; Patwala, Ashish; Tan, Lip-Bun

2005-01-01

It is a prevailing concept in chronic heart failure (CHF) that ventricular remodelling (evaluated via imaging) and neurohormonal activation (via biomarkers) exert major influences, such that the need to subject patients to haemodynamic evaluations and exercise testing has been questioned. We sought to investigate whether exercise and haemodynamic parameters lack independent prognostic value in a cohort of unselected ambulatory patients with mild-moderate CHF. Eighty-five consecutive patients with stable CHF in New York Heart Association functional classes I-IV, aged 55 +/- 12 years, 84% males, left ventricular ejection fraction (LVEF) 37 +/- 15%, participated in this study. Survivors were followed for a median of 5.08 years. All subjects underwent cardiopulmonary exercise testing to measure standard parameters including peak oxygen consumption, exercise duration and blood pressure. A sample of venous blood was taken to determine the N-terminal pro-brain natriuretic peptide (N-BNP) level. Echocardiography was performed at rest to measure LVEF. Predictors of mortality were sought using the Cox proportional hazards model. All-cause mortality was 19% (16 deaths, 95% CI 11-29%). Age and LVEF did not independently predict mortality. Although various parameters including New York Heart Association class, peak oxygen consumption and N-BNP level were all predictive of outcome on univariate analysis, multivariate analysis identified reduced exercise duration and peak systolic blood pressure (SBP) to be the only independent predictors of all-cause mortality. Hazard ratios of 0.78 (95% CI 0.65-0.93, p = 0.007) and 0.79 (95% CI 0.66-0.95, p = 0.01) were associated with an increase in exercise duration of 1 min and 10 mm Hg peak SBP, respectively. Two simple parameters (exercise duration and peak SBP) that are easily measured by standard exercise testing are the strongest independent predictors of mortality which outperform LVEF and N-BNP in ambulatory patients with mild-moderate CHF. Copyright (c) 2005 S. Karger AG, Basel.

Right ventricular to pulmonary artery conduit instead of modified Blalock-Taussig shunt improves postoperative hemodynamics in newborns after the Norwood operation.

PubMed

Mair, Rudolf; Tulzer, Gerald; Sames, Eva; Gitter, Roland; Lechner, Evelyn; Steiner, Jürgen; Hofer, Anna; Geiselseder, Gertraud; Gross, Christoph

2003-11-01

Perioperative mortality, prolonged postoperative recovery after the Norwood procedure, and mortality between stage I and stage II might be related to shunt physiology. A right ventricular to pulmonary artery conduit offers a banded physiology in contrast to a Blalock-Taussig shunt. The purpose of this study was to assess the hemodynamic differences and their consequences in the postoperative course between Norwood patients with a Blalock-Taussig shunt and those with a right ventricular to pulmonary artery conduit. From October 1999 until May 2002, 32 unselected consecutive patients underwent a Norwood procedure at the General Hospital Linz. The first 18 patients received a Blalock-Taussig shunt. In the remaining 14 patients we performed a right ventricular to pulmonary artery conduit. Both groups were compared. The diastolic blood pressure was significantly higher in the right ventricular to pulmonary artery conduit group (P <.001). Despite a higher FIO(2), PO(2) levels tended to be lower in the first 5 postoperative days. At the age of 3 months, catheterization laboratory data showed a lower Qp/Qs ratio in the same group (0.86 [0.78; 1] versus 1.55 [1.15; 1.6]; P =.005) and a higher dp/dt (955 [773; 1110] vs 776 [615; 907]; P =.018). (Descriptive data reflect medians and quartiles [in brackets].) Hospital survival was 72% in the Blalock-Taussig shunt group versus 93% in the right ventricular to pulmonary artery conduit group. Mortality between stage I and stage II was 23% in the Blalock-Taussig shunt group versus 0% in the right ventricular to pulmonary artery conduit group. A higher diastolic blood pressure and a lower Qp/Qs ratio were associated with a more stable and efficient circulation in patients with a right ventricular to pulmonary artery conduit. More intensive ventilatory support was necessary during the first postoperative days. We did not note any adverse effects of the ventriculotomy on ventricular performance.

Comparison of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in predicting mortality in critically ill patients*.

PubMed

Wijdicks, Eelco F M; Kramer, Andrew A; Rohs, Thomas; Hanna, Susan; Sadaka, Farid; O'Brien, Jacklyn; Bible, Shonna; Dickess, Stacy M; Foss, Michelle

2015-02-01

Impaired consciousness has been incorporated in prediction models that are used in the ICU. The Glasgow Coma Scale has value but is incomplete and cannot be assessed in intubated patients accurately. The Full Outline of UnResponsiveness score may be a better predictor of mortality in critically ill patients. Thirteen ICUs at five U.S. hospitals. One thousand six hundred ninety-five consecutive unselected ICU admissions during a six-month period in 2012. Glasgow Coma Scale and Full Outline of UnResponsiveness score were recorded within 1 hour of admission. Baseline characteristics and physiologic components of the Acute Physiology and Chronic Health Evaluation system, as well as mortality were linked to Glasgow Coma Scale/Full Outline of UnResponsiveness score information. None. We recruited 1,695 critically ill patients, of which 1,645 with complete data could be linked to data in the Acute Physiology and Chronic Health Evaluation system. The area under the receiver operating characteristic curve of predicting ICU mortality using the Glasgow Coma Scale was 0.715 (95% CI, 0.663-0.768) and using the Full Outline of UnResponsiveness score was 0.742 (95% CI, 0.694-0.790), statistically different (p = 0.001). A similar but nonsignificant difference was found for predicting hospital mortality (p = 0.078). The respiratory and brainstem reflex components of the Full Outline of UnResponsiveness score showed a much wider range of mortality than the verbal component of Glasgow Coma Scale. In multivariable models, the Full Outline of UnResponsiveness score was more useful than the Glasgow Coma Scale for predicting mortality. The Full Outline of UnResponsiveness score might be a better prognostic tool of ICU mortality than the Glasgow Coma Scale in critically ill patients, most likely a result of incorporating brainstem reflexes and respiration into the Full Outline of UnResponsiveness score.

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

PubMed

Kishore, Amit; Vail, Andy; Majid, Arshad; Dawson, Jesse; Lees, Kennedy R; Tyrrell, Pippa J; Smith, Craig J

2014-02-01

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Clinical significance of specific autoantibodies in juvenile dermatomyositis.

PubMed

Feldman, B M; Reichlin, M; Laxer, R M; Targoff, I N; Stein, L D; Silverman, E D

1996-10-01

To determine the prevalence and clinical association of myositis specific antibodies in an unselected group of patients with juvenile dermatomyositis (DM). The sera of 42 subjects, representing an unselected group of patients from a single center, with juvenile DM and 7 others with idiopathic inflammatory myopathy (IIM) were examined for the presence of myositis specific antibodies by immunodiffusion against calf thymus extract and immunoprecipitation with HeLa extract. Of the subjects with juvenile DM, only 2 had evidence of antibodies specific to myositis (anti-Mi2). Three other patients with juvenile DM had defined autoantibodies not usually considered to be specific to myositis. Two of the 3 subjects had anti-PM-Scl; both developed features of scleroderma after the juvenile DM remitted. The 5 subjects with defined autoantibodies did not differ clinically from the remainder of the subjects with the exception of the late development of scleroderma features in 2. Fourteen other subjects with juvenile DM had unidentified bands on immunoprecipitation, which may represent as yet undiscovered myositis specific antibodies. No myositis specific antibodies were detected in any of the 7 subjects with other IIM syndromes. Based on our findings, we do not recommend routine clinical testing for these antibodies in children with typical juvenile DM. Further study of the unidentified bands seen in our subjects may lead to better understanding of the clinical groupings and etiopathogenesis of childhood myositis.

Implementation of high sensitivity cardiac troponin T measurement in the emergency department.

PubMed

Christ, Michael; Popp, Steffen; Pohlmann, Hella; Poravas, Michail; Umarov, Dina; Bach, Ruth; Bertsch, Thomas

2010-12-01

we examined the diagnostic performance of high sensitivity cardiac troponin T (cTnThs) measurement and its ability to predict risk in unselected patients presenting to the emergency department with acute chest pain. we conducted a retrospective analysis of 137 consecutive patients with chest pain (age range, 66 ± 16 years; 64% male). A final diagnosis of acute myocardial infarction was made using the "old" (cTnT fourth-generation assay, ≥ 0.04 microg/L) or the "new" cutpoint (cTnThs ≥ 0.014 microg/L). the adjudicated final diagnosis of acute myocardial infarction significantly increased from 20 to 35 patients (a 75% increase) and troponin-positive nonvascular cardiac chest pain from 10 to 30 (a 200% increase) using cTnThs. The number of patients with unstable angina or troponin-negative nonvascular cardiac chest pain significantly decreased (P <.05). Diagnostic performance of cTnThs levels at admission was significantly higher compared to cTnT levels (area under the curve [AUC] 0.85 vs AUC 0.70; P <.05). cTnThs levels below the detection limit (<0.003 microg/L) had a negative predictive value of 100% to exclude acute myocardial infarction. The event rate during 6 months of follow-up was low in patients with cTnThs levels <0.014 microg/L, while patients with cTnT levels ≥ 0.04 μg/L were at increased, and patients with cTnThs ≥ 0.014 μg/L and cTnT <0.04 microg/L at intermediate risk of death or recurrent myocardial infarction (P = .002). Risk was highest in chest pain patients with dynamic changes of cTnThs levels >30%. the introduction of cTnThs assay displays an excellent diagnostic performance for the workup of patients with chest pain at the time of their initial presentation. Even small increases of cTnThs indicate increased risk for death or myocardial infarction during follow-up. © 2010 Elsevier Inc. All rights reserved.

BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer.

PubMed

Sakamoto, Ikuko; Hirotsu, Yosuke; Nakagomi, Hiroshi; Ouchi, Hidetaka; Ikegami, Atsushi; Teramoto, Katsuhiro; Amemiya, Kenji; Mochizuki, Hitoshi; Omata, Masao

2016-01-01

The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer. Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing. Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas). In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers. © 2015 American Cancer Society.

Diagnostic profiles of adult psychiatric outpatients with and without attention deficit hyperactivity disorder.

PubMed

Gorlin, Eugenia I; Dalrymple, Kristy; Chelminski, Iwona; Zimmerman, Mark

2016-10-01

Despite growing recognition that attention deficit/hyperactivity disorder (ADHD) is a highly prevalent, impairing, and comorbid disorder that persists into adulthood, reports on the nature and extent of its psychiatric comorbidities have been mixed to date. This study compared the prevalence rates of all major Axis I disorders as well as borderline personality disorder in an unselected sample of adult psychiatric outpatients with and without ADHD. As part of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we administered a DSM-IV-based semi-structured diagnostic interview assessing ADHD and other psychiatric disorders to 1134 patients presenting for initial evaluation at an outpatient psychiatric practice. Logistic regression analyses were used to compare the rates of each disorder in patients with versus without an ADHD diagnosis (both overall and by Combined and Inattentive type). Patients with (versus without) any ADHD diagnosis had significantly higher rates of bipolar disorder, social phobia, impulse control disorders, eating disorders, and BPD, and significantly lower rates of major depressive disorder and adjustment disorder (all p<.05). Patients with (versus without) ADHD-Inattentive type had significantly higher rates of social phobia and eating disorders, whereas those with (versus without) the ADHD-Combined type had significantly higher rates of bipolar disorder, alcohol dependence, and BPD (all p<.05). In this novel investigation of the psychiatric profiles of an unselected sample of treatment-seeking adult outpatients with versus without ADHD, a distinct pattern of comorbidities emerged across subtypes, with implications for the accurate assessment and treatment of patients presenting for psychiatric care. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of chronic cough on quality of life.

PubMed

French, C L; Irwin, R S; Curley, F J; Krikorian, C J

Cough is the most common complaint for which adult patients seek medical care in the United States; however, the reason(s) for this is unknown. To determine whether chronic cough was associated with adverse psychosocial or physical effects on the quality of life and whether the elimination of chronic cough with specific therapy improved these adverse effects. The study design was a prospective before-and-after intervention trial with patients serving as their own controls. Study subjects were a convenience sample of 39 consecutive and unselected adult patients referred for evaluation and management of a chronic, persistently troublesome cough. Baseline data were available for 39 patients and follow-up for 28 patients (22 women and 6 men). At baseline, demographic, Adverse Cough Outcome Survey (ACOS), and Sickness Impact Profile (SIP) data were collected and patients were managed according to a validated, systematic protocol. Following specific therapy for cough, ACOS and SIP instruments were readministered. The ages, sex, duration, and spectra and frequencies of the causes of cough were similar to multiple other studies. At baseline, patients reported a mean +/- SD of 8.6 +/- 4.8 types of adverse occurrences related to cough. There were significant correlations between multiple ACOS items and total, physical, and psychosocial SIP scores. Psychosocial score correlated with total number of symptoms (P<.02). After cough disappeared with treatment, ACOS complaints decreased to a mean +/- SD of 1.9 +/- 3.2 (P<.0001) as did total (mean +/- SD, 4.8 +/- 4.5 to 1.8 +/- 2.2) (P= .004), psychosocial (mean +/- SD, 4.2 +/- 6.8 to 0.8 +/- 2.3) (P = .004), and physical (mean +/- SD, 2.2 +/- 2.9 to 0.9 +/- 1.8) (P = .05) SIP scores. Multiple linear regression analysis showed that 54% of variability of the psychosocial SIP score was explained by 4 ACOS items while none of the physical score was explained. Chronic cough was associated with deterioration in patients' quality of life. The health-related dysfunction was most likely psychosocial. The ACOS and SIP appear to be valid tools in assessing the impact of chronic cough.

Model of inter-cell interference phenomenon in 10 nm magnetic tunnel junction with perpendicular anisotropy array due to oscillatory stray field from neighboring cells

NASA Astrophysics Data System (ADS)

Ohuchida, Satoshi; Endoh, Tetsuo

2018-06-01

In this paper, we propose a new model of inter-cell interference phenomenon in a 10 nm magnetic tunnel junction with perpendicular anisotropy (p-MTJ) array and investigated the interference effect between a program cell and unselected cells due to the oscillatory stray field from neighboring cells by Landau–Lifshitz–Gilbert micromagnetic simulation. We found that interference brings about a switching delay in a program cell and excitation of magnetization precession in unselected cells even when no programing current passes through. The origin of interference is ferromagnetic resonance between neighboring cells. During the interference period, the precession frequency of the program cell is 20.8 GHz, which synchronizes with that of the theoretical precession frequency f = γH eff in unselected cells. The disturbance strength of unselected cells decreased to be inversely proportional to the cube of the distance from the program cell, which is in good agreement with the dependence of stray field on the distance from the program cell calculated by the dipole approximation method.

Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study.

PubMed

Carstensen, Jeppe West; Chehri, Mahtab; Schønning, Kristian; Rasmussen, Steen Christian; Anhøj, Jacob; Godtfredsen, Nina Skavlan; Andersen, Christian Østergaard; Petersen, Andreas Munk

2018-05-03

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 10 9 , Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

BRCAsearch: written pre-test information and BRCA1/2 germline mutation testing in unselected patients with newly diagnosed breast cancer.

PubMed

Nilsson, Martin P; Törngren, Therese; Henriksson, Karin; Kristoffersson, Ulf; Kvist, Anders; Silfverberg, Barbro; Borg, Åke; Loman, Niklas

2018-02-01

To evaluate a simplified method of pre-test information and germline BRCA1/2 mutation testing. In a prospective, single-arm study, comprehensive BRCA1/2 testing was offered to unselected patients with newly diagnosed breast cancer at three hospitals in south Sweden (BRCAsearch, ClinicalTrials.gov Identifier: NCT02557776). Pre-test information was provided by a standardized invitation letter, but the patients could contact a genetic counselor for telephone genetic counseling if they felt a need for that. Noncarriers were informed about the test result through a letter. Mutation carriers were contacted and offered an appointment for in-person post-test genetic counseling. During the period Feb 2, 2015-Aug 26, 2016, eight hundred and eighteen patients were invited to participate in the study. Through Jan 31, 2017, five hundred and forty-two (66.2%) of them consented to analysis of BRCA1 and BRCA2. Eleven pathogenic mutations were found (BRCA1, n = 2; BRCA2, n = 9), corresponding to a mutation prevalence of 2.0%. Six out of 11 fulfilled the Swedish BRCA testing criteria, and 9 out of 11 fulfilled the NCCN testing criteria. None of the BRCA-associated tumors were of the luminal A-like subtype. Very few patients contacted us for telephone genetic counseling or practical questions, suggesting that a majority felt that the written pre-test information was sufficient for them to make a decision on testing. Streamlining the process of pre-test information, genetic testing, and delivery of test results was feasible and was associated with an uptake of genetic testing in 2/3 of the breast cancer patients.

Prevalence and Phenotype of Sleep Disorders in 60 Adults With Prader-Willi Syndrome.

PubMed

Ghergan, Adelina; Coupaye, Muriel; Leu-Semenescu, Smaranda; Attali, Valérie; Oppert, Jean-Michel; Arnulf, Isabelle; Poitou, Christine; Redolfi, Stefania

2017-12-01

Excessive sleepiness is a common symptom in Prader-Willi syndrome (PWS), and it negatively impacts the quality of life. Obstructive sleep apnea and narcolepsy phenotypes have been reported in PWS. We characterized sleep disorders in a large cohort of adults with PWS. All consecutive patients with genetically confirmed PWS unselected for sleep-related symptoms, underwent a clinical interview, polysomnography, and multiple sleep latency tests (MSLT, n = 60), followed by long-term (24 hours) polysomnography (n = 22/60). Among 60 adults evaluated (57% female, aged 25 ± 10 years, body mass index: 39 ± 12 kg/m2), 67% reported excessive sleepiness. According to the sleep study results, 43% had a previously unrecognized hypersomnia disorder, 15% had an isolated sleep breathing disorder, 12% had combined hypersomnia disorder and untreated breathing sleep disorder, and only 30% had normal sleep. Isolated hypersomnia disorder included narcolepsy in 35% (type 1, n = 1, and type 2, n = 8), hypersomnia in 12% (total sleep time >11 hours, n = 2, and MSLT <8 minutes, n = 1), and borderline phenotype in 53% (≥2 sleep onset in REM periods and MSLT >8 minutes, n = 10, and 8 minutes < MSLT < 10 minutes, n = 4). Sleep breathing disorders, isolated and combined, included obstructive sleep apnea (n = 14, already treated in seven), sleep hypoxemia (n = 1) and previously undiagnosed hypoventilation (n = 5). Modafinil was taken by 16 patients (well tolerated in 10), resulting in improved sleepiness over a mean 5-year follow-up period. Sleepiness affects more than half of adult patients with PWS, with a variety of hypersomnia disorder (narcolepsy, hypersomnia, and borderline phenotypes) and breathing sleep disorders. Earlier diagnosis and management of sleep disorders may improve sleepiness, cognition, and behavior in these patients. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com

The GALA study: relationship between galectin-3 serum levels and short- and long-term outcomes of patients with acute heart failure.

PubMed

Miró, Òscar; González de la Presa, Bernardino; Herrero-Puente, Pablo; Fernández Bonifacio, Rosa; Möckel, Martin; Mueller, Christian; Casals, Gregori; Sandalinas, Silvia; Llorens, Pere; Martín-Sánchez, Francisco Javier; Jacob, Javier; Bedini, José Luis; Gil, Víctor

2017-12-01

We tested the hypothesis that early measurement of galectin-3 at the emergency department (ED) during an episode of acute heart failure (AHF) allows predicting short- and long-term outcomes. We performed an exploratory study including 115 patients consecutively diagnosed with AHF in a single ED. Clinical and analytical variables were recorded. The primary endpoint was 30-day all-cause mortality, and secondary endpoints were 30-day composite outcome (death, rehospitalization or ED reconsultation, whichever first) and 1-year mortality. Seven patients (6.1%) died within 30 days and 43 (37.4%) within 1 year. The 30-day composite endpoint was observed in 21.1% of patients. Galectin-3 was correlated with NT-proBNP and the glomerular filtration rate but not with age and s-cTnI. Measured at time of ED arrival, galectin-3 showed good discriminatory capacity for 30-day mortality (AUC ROC: 0.732; 95% CI 0.512-0.953; p = 0.041) but not for 1-year mortality (0.521; 0.408-0.633; p = 0.722). Patients with galectin-3 concentrations >42 μg/L had an OR = 7.67(95%CI = 1.57-37.53; p = 0.012) for 30-day mortality. Conversely, NT-proBNP only showed predictive capacity for 1-year mortality (0.642; 0.537-0.748; p = 0.014). Patients with NT-proBNP concentrations >5400 ng/L had an OR = 4.34 (95%CI = 1.93-9.77; p < 0.001) for 1-year mortality. These increased short- (galectin-3) and long-term (NT-proBNP) risks remained significant after adjustment for age or renal function. s-cTnI failed in both short- and long term death prediction. No biomarker predicted the short-term composite endpoint. These results suggest that galectin-3 could help to monitor the risk of short-term mortality in unselected patients with AHF attended in the ED.

Acute heart failure in the emergency department: a follow-up study.

PubMed

Fabbri, Andrea; Marchesini, Giulio; Carbone, Giorgio; Cosentini, Roberto; Ferrari, Annamaria; Chiesa, Mauro; Bertini, Alessio; Rea, Federico

2016-02-01

Acute heart failure (AHF) is a major public health issue due to high incidence and poor prognosis. Only a few studies are available on the long-term prognosis and on outcome predictors in the unselected population attending the emergency department (ED) for AHF. We carried out a 1-year follow-up analysis of 1234 consecutive patients from selected Italian EDs from January 2011 to June 2012 for an episode of AHF. Their prognosis and outcome-associated factors were tested by Cox proportional hazard model. Patients' mean age was 84, with 66.0% over 80 years and 56.2% females. Comorbidities were present in over 50% of cases, principally a history of acute coronary syndrome, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, valvular heart disease. Death occurred within 6 h in 24 cases (1.9%). At 30-day follow-up, death was registered in 123 cases (10.0%): 110 cases (89.4%) died of cardiovascular events and 13 (10.6%) of non-cardiovascular causes (cancer, gastrointestinal hemorrhages, sepsis, trauma). At 1-year follow-up, all-cause death was recorded in 50.1% (over 3 out of 4 cases for cardiovascular origin). Six variables (older age, diabetes, systolic arterial pressure <110 mm/Hg, high NT pro-BNP, high troponin levels and impaired cognitive status) were selected as outcome predictors, but with limited discriminant capacity (AUC = 0.649; SE 0.015). Recurrence of AHF was registered in 31.0%. The study identifies a cluster of variables associated with 1-year mortality in AHF, but their predictive capacity is low. Old age and the presence of comorbidities, in particular diabetes are likely to play a major role in dictating the prognosis.

Sample features associated with success rates in population-based EGFR mutation testing.

PubMed

Shiau, Carolyn J; Babwah, Jesse P; da Cunha Santos, Gilda; Sykes, Jenna R; Boerner, Scott L; Geddie, William R; Leighl, Natasha B; Wei, Cuihong; Kamel-Reid, Suzanne; Hwang, David M; Tsao, Ming-Sound

2014-07-01

Epidermal growth factor receptor (EGFR) mutation testing has become critical in the treatment of patients with advanced non-small-cell lung cancer. This study involves a large cohort and epidemiologically unselected series of EGFR mutation testing for patients with nonsquamous non-small-cell lung cancer in a North American population to determine sample-related factors that influence success in clinical EGFR testing. Data from consecutive cases of Canadian province-wide testing at a centralized diagnostic laboratory for a 24-month period were reviewed. Samples were tested for exon-19 deletion and exon-21 L858R mutations using a validated polymerase chain reaction method with 1% to 5% detection sensitivity. From 2651 samples submitted, 2404 samples were tested with 2293 samples eligible for analysis (1780 histology and 513 cytology specimens). The overall test-failure rate was 5.4% with overall mutation rate of 20.6%. No significant differences in the failure rate, mutation rate, or mutation type were found between histology and cytology samples. Although tumor cellularity was significantly associated with test-success or mutation rates in histology and cytology specimens, respectively, mutations could be detected in all specimen types. Significant rates of EGFR mutation were detected in cases with thyroid transcription factor (TTF)-1-negative immunohistochemistry (6.7%) and mucinous component (9.0%). EGFR mutation testing should be attempted in any specimen, whether histologic or cytologic. Samples should not be excluded from testing based on TTF-1 status or histologic features. Pathologists should report the amount of available tumor for testing. However, suboptimal samples with a negative EGFR mutation result should be considered for repeat testing with an alternate sample.

Validation of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinomas.

PubMed

Mosquera, Juan-Miguel; Dal Cin, Paola; Mertz, Kirsten D; Perner, Sven; Davis, Ian J; Fisher, David E; Rubin, Mark A; Hirsch, Michelle S

2011-09-01

Renal cell carcinomas (RCCs) with an Xp11.2 translocation predominantly affect young patients, and can present at an advanced stage. However, more cases in older patients and incidentally detected cancers at earlier stages are also being identified. As the histology of Xp11.2 RCCs overlaps with clear cell and papillary RCCs, it is not infrequent that Xp11.2 RCCs are overlooked and misdiagnosed. The objective of this study was to validate the use of fluorescence in-situ hybridization (FISH) for identifying Xp11.2 RCCs. One hundred fifty-eight consecutive, unselected renal tumors were evaluated in tissue microarrays, including 109 clear cell RCCs, 20 papillary RCCs, 3 RCCs with mixed papillary and clear cell features, 1 Xp11.2 translocation RCC, 8 chromophobe RCCs, 10 oncocytomas, and 7 angiomyolipomas. FISH evaluation was performed blinded to karyotype data, available in about two-thirds of cases. Furthermore, conventional sections of 4 Xp11.2 RCCs, 4 RCCs with mixed papillary and clear cell features, and 4 cases of alveolar soft part sarcoma (the latter for control purposes) were also assessed by FISH. Break-apart signals were homogeneously identified throughout tumor cells in 2 cases from the tissue microarrays including 1 known Xp11.2 RCC and 1 misdiagnosed Xp11.2 RCC. All conventional sections from the Xp11.2 RCC and alveolar soft part sarcoma cases were positive for the TFE3 rearrangement by FISH. All remaining cases were negative. Our study shows the clinical application of FISH in formalin-fixed, paraffin-embedded tissue for detection of Xp11.2 translocation RCCs and other tumors with this genetic aberration.

Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma

PubMed Central

Wienemann, Tobias; Chantelau, Ernst A.; Koller, Armin

2014-01-01

Introduction and objective Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy). Design and methods A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®). Results In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively. Conclusion Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking. PMID:25397867

Ethnic differences in the frequency of subtypes of childhood acute lymphoblastic leukemia: results of the Malaysia-Singapore Leukemia Study Group.

PubMed

Ariffin, Hany; Chen, Siew-Peng; Kwok, Cecilia S; Quah, Thuan-Chong; Lin, Hai-Peng; Yeoh, Allen E J

2007-01-01

Childhood acute lymphoblastic leukemia (ALL) is clinically heterogeneous with prognostically and biologically distinct subtypes. Although racial differences in frequency of different types of childhood ALL have been reported, many are confounded by selected or limited population samples. The Malaysia-Singapore (MA-SPORE) Leukemia Study Group provided a unique platform for the study of the frequency of major subgroups of childhood ALL in a large cohort of unselected multiethnic Asian children. Screening for the prognostically important chromosome abnormalities (TEL-AML1, BCR-ABL, E2A-PBX1, and MLL) using multiplex reverse-transcription polymerase chain reaction was performed on 299 consecutive patients with ALL at 3 study centers (236 de novo, 63 at relapse), with the ethnic composition predominantly Chinese (51.8%) and Malay (34.8%). Reverse-transcription polymerase chain reaction was successful in 278 (93%) of cases screened. The commonest fusion transcript was TEL-AML1 (19.1%) followed by BCR-ABL (7.8%), MLL rearrangements (4.2%), and E2A-PBX1 (3.1%). Chinese have a significantly lower frequency of TEL-AML1 (13.3% in de novo patients) compared with Malays (22.2%) and Indians (21.7%) (P=0.04). Malays have a lower frequency of T-ALL (6.2%) compared with the Chinese and Indians (9.8%). Both Malays (7.4%) and Chinese (5.0%) have significantly higher frequency of BCR-ABL compared with the Indian population (P<0.05) despite a similar median age at presentation. Our study suggests that there are indeed significant and important racial differences in the frequency of subtypes of childhood ALL. Comprehensive subgrouping of childhood ALL may reveal interesting population frequency differences of the various subtypes, their risk factors and hopefully, its etiology.

Piezosurgery for orbital decompression surgery in thyroid associated orbitopathy.

PubMed

Ponto, Katharina A; Zwiener, Isabella; Al-Nawas, Bilal; Kahaly, George J; Otto, Anna F; Karbach, Julia; Pfeiffer, Norbert; Pitz, Susanne

2014-12-01

The purpose of this study was to assess a piezosurgical device as a novel tool for bony orbital decompression surgery. At a multidisciplinary orbital center, 62 surgeries were performed in 40 patients with thyroid associated orbitopathy (TAO). Within this retrospective case-series, we analyzed the medical records of these consecutive unselected patients. The reduction of proptosis was the main outcome measure. Indications for a two (n = 27, 44%) or three wall (35, 56%) decompression surgery were proptosis (n = 50 orbits, 81%) and optic neuropathy (n = 12, 19%). Piezosurgery enabled precise bone cuts without intraoperative complications. Proptosis decreased from 23.6 ± 2.8 mm (SD) by 3 mm (95% CI: -3.6 to -2.5 mm) after surgery and stayed stable at 3 months (-3 mm, 95% CI: -3.61 to -2.5 mm, p < 0.001, respectively). The effect was higher in those with preoperatively higher values (>24 mm versus ≤ 24 mm: -3.4 mm versus -2.81 mm before discharge from hospital and -4.1 mm versus -2.1 mm at 3 months: p < 0.001, respectively). After a mean long-term follow-up period of 14.6 ± 10.4 months proptosis decreased by further -0.7 ± 2.0 mm (p < 0.001). Signs of optic nerve compression improved after surgery. Infraorbital hypesthesia was present in 11 of 21 (52%) orbits 3 months after surgery. The piezosurgical device is a useful tool for orbital decompression surgery in TAO. By cutting bone selectively, it is precise and reduces the invasiveness of surgery. Nevertheless, no improvement in outcome or reduction in morbidity over conventional techniques has been shown so far. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Anosognosia for obvious visual field defects in stroke patients.

PubMed

Baier, Bernhard; Geber, Christian; Müller-Forell, Wiebke; Müller, Notger; Dieterich, Marianne; Karnath, Hans-Otto

2015-01-01

Patients with anosognosia for visual field defect (AVFD) fail to recognize consciously their visual field defect. There is still unclarity whether specific neural correlates are associated with AVFD. We studied AVFD in 54 patients with acute stroke and a visual field defect. Nineteen percent of this unselected sample showed AVFD. By using modern voxelwise lesion-behaviour mapping techniques we found an association between AVFD and parts of the lingual gyrus, the cuneus as well as the posterior cingulate and corpus callosum. Damage to these regions appears to induce unawareness of visual field defects and thus may play a significant role for conscious visual perception.

Case-finding for coeliac disease in secondary care: a prospective multicentre UK study.

PubMed

Mooney, Peter D; Leeds, John S; Libzo, Nafan; Sidhu, Reina; Evans, Kate E; Hall, Emma J; Jandu, Veerinder S; Hopper, Andrew D; Basumani, Pandurangan; Dear, Keith L; McAlindon, Mark E; Sanders, David S

2014-01-01

Coeliac disease affects 1% of the population. Despite this high prevalence, the majority of individuals are undetected. Many patients present with subtle symptoms which may also contribute to under diagnosis. Our aim was to determine the relative importance of different presenting characteristics. Unselected gastroenterology patients referred to 4 hospitals in South Yorkshire were investigated for coeliac disease. Diagnosis was based on positive serology and the presence of villous atrophy. Odds ratios were calculated for presenting characteristics and multivariate analysis performed to identify independent risk factors. 4089 patients were assessed (41.5% male, mean age 55.8 ± 18.2 years); 129 had coeliac disease (3.2%, 95% CI 2.6-3.7%). Multivariate analysis of patients referred to secondary care showed family history of coeliac disease (OR 1.26, p < 0.0001), anaemia (OR 1.03, p < 0.0001) and osteoporosis (OR 1.1, p = 0.006) were independent risk factors for diagnosis of coeliac disease. When compared to population controls, diarrhoea (OR 4.1, p < 0.0001), weight loss (OR 2.7, p = 0.02), irritable bowel syndrome symptoms (OR 3.2, p = 0.005) thyroid disease (OR 4.4, p = 0.01) and diabetes (OR 3.0, p = 0.05) were also associated with increased coeliac disease risk. Coeliac disease accounts for 1 in 31 referrals in secondary care to unselected gastroenterology clinics. A low threshold for coeliac disease testing should be adopted. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Impact of severe tricuspid regurgitation on accuracy of systolic pulmonary arterial pressure measured by Doppler echocardiography: Analysis in an unselected patient population.

PubMed

Fei, Beini; Fan, Ting; Zhao, Ling; Pei, Xiaoli; Shu, Xianhong; Fang, Xiaoyan; Cheng, Leilei

2017-07-01

Pulmonary arterial pressure is an important index in cardiovascular disorders, especially for pulmonary hypertension (PH). Doppler echocardiography (DE) is widely used as a noninvasive method to assess pulmonary arterial pressure. However, recent studies have found several hemodynamic factors that affect its accuracy in estimating systolic pulmonary arterial pressure (sPAP). But the effect of tricuspid regurgitation (TR) has not been investigated. Therefore, our study is aimed to determine whether the severity of TR will affect the accuracy of sPAP measured by DE in an unselected patient population. We retrospectively studied 177 patients who underwent DE and right heart catheterization (RHC) examinations. Patients were categorized into 3 groups according to the severity of TR (mild, moderate, and severe). The discrepancy in sPAP measured by DE and RHC was calculated and compared in each group. Determinants of discordant results between two methods were also evaluated. Age, gender, interval between DE and RHC, sequence of DE and RHC were similar among groups (all P>.05). Differences in sPAP, RAP, and tricuspid regurgitation pressure gradient (TR-PG) were similar in group 1 and 2 (all P>.05), while all significantly higher in group 3 (all P<.05). The difference in sPAP between DE and RHC was affected independently by severe TR and severe PH (both P<.05). Severe TR and severe PH affect the accuracy of sPAP measured by DE. Modification of echocardiographic sPAP measurements by taking into consideration of these factors may lead to reduced systemic errors. © 2017, Wiley Periodicals, Inc.

The risk of gastric cancer in carriers of CHEK2 mutations.

PubMed

Teodorczyk, Urszula; Cybulski, Cezary; Wokołorczyk, Dominika; Jakubowska, Anna; Starzyńska, Teresa; Lawniczak, Małgorzata; Domagała, Paweł; Ferenc, Katarzyna; Marlicz, Krzysztof; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Narod, Steven A; Lubiński, Jan

2013-09-01

CHEK2 is a tumor suppressor gene whose functions are central to the induction of cell cycle arrest and apoptosis following DNA damage. Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied. In Poland, there are four known founder alleles of CHEK2; three alleles are protein truncating (1100delC, IVS2G>A, del5395) and the other is a missense variant (I157T). We examined the frequencies of four Polish founder mutations in the CHEK2 gene in 658 unselected gastric cancer patients, in 154 familial gastric cancer patients and in 8,302 controls. A CHEK2 mutation was seen in 57 of 658 (8.7 %) unselected patients with gastric cancer compared to 480 of 8,302 (5.8 %) controls (OR 1.6, p = 0.004). A CHEK2 mutation was present in 19 of 154 (12.3 %) familial cases (OR = 2.3, p = 0.001). The odds ratio for early onset (<50 years) gastric cancer was higher (2.1, p = 0.01), than for cases diagnosed at age of 50 or above (OR 1.4, p = 0.05). Truncating mutations of CHEK2 were associated with higher risk (OR = 2.1, p = 0.02) than the missense mutation I157T (OR = 1.4, p = 0.04). CHEK2 mutations predispose to gastric cancer, in particular to young-onset cases.

Diagnosis of myocardial infarction using the new universal definition: is it enough for risk stratification and guiding decision for revascularization?

PubMed

Calé, Rita; Ferreira, Jorge; Aguiar, Carlos; Santos, Nuno; Carmo, Pedro; Figueira, João; Raposo, Luis; Gonçalves, Pedro; Silva, José Aniceto

2010-12-01

Abstract Objectives: Evaluate the new ESC/ACCF/AHA/WHF universal definition of myocardial infarction (MI) in relation to its prognostic implications and the role for guiding decision for revascularization. It was also compared with the multivariable based GRACE Risk Score (GRS). Single centre registry of 389 consecutive patients admitted with non-ST-segment elevation (NSTE) ACS. We calculated the adjusted HR & 95%CI for death/MI at 30-days and one-year follow-up, between the presence or absence of MI using: (1) universal definition: > 99th URL for cTnI (> 0.06 ng/ml) or MBm (> 3.2 ng/ml); (2) MBm > 2 × URL (> 12.2 ng/ml); 3) old WHO: MBact > 2 × URL (> 32U/l). Logistic analysis was performed to test the interaction between tertiles of biomarkers or GRS and the effect of revascularization on the outcome. The universal definition increased the incidence of MI in 3.5-fold for cTnI, but was not an independent predictor of outcome. The GRS was the only independent predictor of prognosis at 30-days and one-year. The interaction with the prognostic impact of revascularization was only present for the GRS categorized by tertiles. In a contemporary unselected population with NSTE-ACS, the universal definition of MI alone was not adequate for risk assessment and revascularization decision making. These purposes were fully addressed with the GRS.

How should a district general hospital immunology service screen for anti-nuclear antibodies? An ‘in-the-field’ audit

PubMed Central

Hira-Kazal, R; Shea-Simonds, P; Peacock, J L; Maher, J

2015-01-01

Anti-nuclear antibody (ANA) testing assists in the diagnosis of several immune-mediated disorders. The gold standard method for detection of these antibodies is by indirect immunofluorescence testing on human epidermoid laryngeal carcinoma (HEp-2) cells. However, many laboratories test for these antibodies using solid-phase assays such as enzyme-linked immunosorbent assay (ELISA), which allows for higher throughput testing at reduced cost. In this study, we have audited the performance of a previously established ELISA assay to screen for ANA, making comparison with the gold standard HEp-2 immunofluorescence test. A prospective and unselected sample of 89 consecutive ANA test requests by consultant rheumatologists were evaluated in parallel over a period of 10 months using both tests. ELISA and HEp-2 screening assays yielded 40 (45%) and 72 (81%) positive test results, respectively, demonstrating lack of concordance between test methods. Using standard and clinical samples, it was demonstrated that the ELISA method did not detect several ANA with nucleolar, homogeneous and speckled immunofluorescence patterns. None of these ELISANEG HEp-2POS ANA were reactive with a panel of six extractable nuclear antigens or with double-stranded DNA. Nonetheless, 13 of these samples (15%) originated from patients with recognized ANA-associated disease (n = 7) or Raynaud's phenomenon (n = 6). We conclude that ELISA screening may fail to detect clinically relevant ANA that lack defined specificity for antigen. PMID:25412573

Primary angioplasty and routine utilization of thrombus aspiration devices: feasibility and results in a consecutive series of 486 patients.

PubMed

Varbella, Ferdinando; Gagnor, Andrea; Luceri, Stefania; Bongioanni, Sergio; Nannini, Cristiana; Masi, Andrea Sibona; Tripodi, Rosario; Pron, Paolo Giay; Mainardi, Loredana; Badalì, Antonino; Conte, Maria R

2007-04-01

Primary percutaneous transluminal coronary angioplasty (PTCA) is the treatment of choice for acute ST-segment elevation myocardial infarction (STEMI) in high-volume centres with experienced operators, but is often limited by a suboptimal microvascular perfusion due to distal embolization and impaired myocardial perfusion. The present study investigates whether routine use of thrombus aspiration (TA) devices is feasible in daily practice, along with its safety and effectiveness. This study is based on a series of 486 consecutive STEMI patients treated at our single institution by the same three operators (from 2001 to 2005). They underwent primary PTCA with or without TA according to these angiographic features: infarct related artery (IRA) diameter>or=3 mm; thrombotic occlusion or angiographic evidence of thrombus; absence of severe proximal tortuosity or calcification. We evaluate the efficacy of TA in terms of procedural success, coronary thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), resolution>or=50% of ST segment elevation, and clinical events during hospital stay and at 6-month follow-up. A total of 486 primary PTCAs were performed, 217 (44.6%) with TA as a first device using RESCUE (n=65), EXPORT (n=140) and DIVER-CE (n=12) catheters. In 141 (65%) cases, macroscopic material was aspirated. The patients submitted to TA were more often males (84.7% versus 71.7%, P<0.05) and younger (age: 61.02+/-11.91 versus 64.47+/-10.59 years, P<0.01) than patients treated with traditional PTCA and the IRA was more frequently occluded at angiography (basal TIMI 0: 70.5% versus 47.9%). Application of the TA did not increase the complexity of the procedure (door-to-balloon times, minutes of fluoroscopy and amount of dye). TA alone was effective to restore TIMI 3 flow in 187 cases (86.2%) as a first device and in three other cases (1.4%) after predilatation with balloon. Direct stenting without predilatation was possible in 144 cases (66.4%) after TA. TA was not effective in 27 cases (12.4%) and this subgroup had both angiographic and clinical unfavourable results in comparison with the effective TA group (final TIMI 1 in 11.1% versus 0.5%, P<0.015; final MBG 1 in 55.5% versus 9.5%, P<0.001; lack of ST segment resolution>or=50% in 44.4% versus 7.9%, P<0.001; in-hospital mortality 14.8% versus 2.6%, P<0.05 and mortality at 6 months 18.5% versus 3.1%, P<0.05). In the whole TA population, final TIMI 3 flow was achieved in 203 cases (93.5%), final MBG 3 in 145 cases (66.8%) and ST segment resolution>or=50% in 185 cases (85.2%), in-hospital mortality was 4.1% and cumulative mortality at 6-month follow-up was 5.5%. In our case series, 486 consecutive unselected patients with STEMI were treated in a primary PTCA high-volume centre using TA devices. Our study demonstrates that, in STEMI patients treated with primary PTCA, a routine strategy with TA before angioplasty guided by angiographic selection criteria is feasible in almost 50% of cases, is safe and effective, does not increase procedural time and offers good results in terms of tissue perfusion, both epicardial (TIMI flow) and myocardial (MBG, ST regression). When successfully performed, TA identifies a population with favourable in-hospital and 6-month outcome.

Clinical spectrum of Kawasaki disease in infants younger than 6 months of age.

PubMed

Burns, J C; Wiggins, J W; Toews, W H; Newburger, J W; Leung, D Y; Wilson, H; Glodé, M P

1986-11-01

We report an unselected series of eight patients younger than 6 months of age with Kawasaki disease evaluated between January 1982 and May 1984. The incidence of coronary artery aneurysms (six patients) and the mortality (two patients) were unusually high in this small series. Because of the confusing clinical presentation in three patients, diagnosis was delayed until pathologic or echocardiographic evidence of coronary vasculitis or aneurysm was discovered. The currently accepted clinical criteria for Kawasaki disease may not always identify patients with the pathologic findings of the syndrome who are younger than 6 months of age. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin.

Self-efficacy, social support and service integration at medical cannabis facilities in the San Francisco Bay area of California.

PubMed

Reiman, Amanda E

2008-01-01

In an effort to examine and possibly utilise the community-based, bottom-up service design of medical cannabis facilities in the San Francisco Bay area of California, 130 adults who had received medical cannabis recommendations from a physician were surveyed at seven facilities to describe the social service aspects of these unique, community-based programmes. This study used an unselected consecutive sample and cross-sectional survey design that included primary data collection at the medical cannabis facilities themselves. In this exploratory study, individual level data were collected on patient demographics and reported patient satisfaction as gathered by the Patient Satisfaction Questionnaire III. Surveys were filled out on site. In the case of a refusal, the next person was asked. The refusal rate varied depending on the study site and ranged between 25% and 60%, depending on the facility and the day of sampling. Organisational-level data, such as operating characteristics and products offered, created a backdrop for further examination into the social services offered by these facilities and the attempts made by this largely unregulated healthcare system to create a community-based environment of social support for chronically ill people. Informal assessment suggests that chronic pain is the most common malady for which medical cannabis is used. Descriptive statistics were generated to examine sample- and site-related differences. Results show that medical cannabis patients have created a system of dispensing medical cannabis that also includes services such as counselling, entertainment and support groups - all important components of coping with chronic illness. Furthermore, patients tend to be male, over 35, identify with more than one ethnicity, and earn less than US$20 000 annually. Levels of satisfaction with facility care were fairly high, and higher than nationally reported satisfaction with health care in the USA. Facilities tended to follow a social model of cannabis care, including allowing patients to use medicine on site and offering social services. This approach has implications for the creation and maintenance of a continuum of care among bottom-up social and health services agencies.

Negative Effects on Psychological Health and Quality of Life of Genuine Irritable Bowel Syndrome-type Symptoms in Patients With Inflammatory Bowel Disease.

PubMed

Gracie, David J; Williams, Christopher J M; Sood, Ruchit; Mumtaz, Saqib; Bholah, M Hassan; Hamlin, P John; Ford, Alexander C

2017-03-01

Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with inflammatory bowel disease (IBD), but it is unclear whether this relates to occult IBD activity. We attempted to resolve this issue in a secondary care population by using a cross-sectional study design. We analyzed Rome III IBS symptoms, disease activity indices, and psychological, somatization, and quality of life data from 378 consecutive, unselected adult patients with IBD seen in clinics at St James's University Hospital in Leeds, United Kingdom from November 2012 through June 2015. Participants provided a stool sample for fecal calprotectin (FC) analysis; levels ≥250 μg/g were used to define mucosal inflammation. By using symptom data and FC levels we identified 4 distinct groups of patients: those with true IBS-type symptoms (IBS-type symptoms with FC levels <250 μg/g, regardless of disease activity indices), quiescent IBD (no IBS-type symptoms with FC levels <250 μg/g, regardless of disease activity indices), occult inflammation (normal disease activity indices and FC levels ≥250 μg/g, regardless of IBS symptom status), or active IBD (abnormal disease activity indices with FC levels ≥250 μg/g, regardless of IBS symptom status). We compared characteristics between these groups. Fifty-seven of 206 patients with Crohn's disease (27.7%) and 34 of 172 patients with ulcerative colitis (19.8%) had true IBS-type symptoms. Levels of psychological comorbidity and somatization were significantly higher among patients with true IBS-type symptoms than patients with quiescent IBD or occult inflammation. Quality of life levels were also significantly reduced compared with patients with quiescent disease or occult inflammation and were similar to those of patients with active IBD. By using FC levels ≥100 μg/g to define mucosal inflammation, we found a similar effect of IBS-type symptoms on psychological health and quality of life. In a cross-sectional study, we identified a distinct group of patients with IBD and genuine IBS-type symptoms in the absence of mucosal inflammation. These symptoms had negative effects on psychological well-being and quality of life to the same degree as active IBD. New management strategies are required for this patient group. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma.

PubMed Central

Griffiths, A P; Wyatt, J; Jack, A S; Dixon, M F

1994-01-01

A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma. PMID:7876391

Degree of Stereotypic Responding by Hyperactive, Learning Disabled, and Unselected Children in a Computer-Controlled Task.

ERIC Educational Resources Information Center

Metzger, Mary Ann; Freund, Lisa

The present research assessed the ability to attend to relevant information in the presence of irrelevant distraction in hyperactive (H), learning disabled (LD), and unselected (US) children. A total of 20 LD, 20 H, and 20 US children divided into younger and older age groups participated in the study. Younger children were between 94 and 104…

[Corifollitropin alfa in women stimulated for the first time in in vitro fertilization programme].

PubMed

Vraná-Mardešićová, N; Vobořil, J; Melicharová, L; Jelínková, L; Vilímová, Š; Mardešić, T

2017-01-01

To compare results after stimulation with corifollitropin alfa (Elonva) in unselected group of women entering for the first time in in vitro fertilization programme (IVF) with results from Phase III randomized trials with selected groups of women. Prospective study. Sanatorium Pronatal, Praha. 40 unselected women with adequat ovarian reserve entering for the first time in IVF programme were stimulated with corifollitropin alfa and GnRH antagonists. Avarage age in the study group was 32,8 years (29-42 years), women younger then 36 and less then 60 kg received Elonva 100 µg , all others (age > 36 let, weight > 60 kg) Elonva 150 µg. Five days after egg retrieval one blastocyst was transferred (single embryo transfer - eSET). Our results were compared with the resuls in higly selected groups of women from Phase III randomized trials. After stimulation with corifollitropin alfa and GnRH antagonists on average 10,6 (9,2 ± 4,2) eggs could be retrieved, among them 7,3 (6,6 ± 3,9) were M II oocytes (68,9%) and fertilisation rate was 84,6%. After first embryo transfer ("fresh" embryos and embryos from "freeze all" cycles) 14 pregnancies were achieved (37,8%), three pregnancies were achieved later from transfer of frozen-thawed embryos (cumulative pregnancy rate 45,9%). There were three abortions. No severe hyperstimulation syndrom occured. Our results in unselected group of women stimulated for the first in an IVF programme with corifollitropin alfa are fully comparable with results published in randomized trials with selected group of patiens. Corifollitropin alfa in combination with daily GnRH antagonist can be successfully used in normal-responder patients stimulated for the first time in an IVF programmeKeywords: corifollitropin alfa, GnRH antagonists, ovarian stimulation, pregnancy.

Study protocol: first nationwide comparative audit of acute lower gastrointestinal bleeding in the UK.

PubMed

Oakland, Kathryn; Guy, Richard; Uberoi, Raman; Seeney, Frances; Collins, Gary; Grant-Casey, John; Mortensen, Neil; Murphy, Mike; Jairath, Vipul

2016-08-04

Acute lower gastrointestinal bleeding (LGIB) is a common indication for emergency hospitalisation worldwide. In contrast to upper GIB, patient characteristics, modes of investigation, transfusion, treatment and outcomes are poorly described. There are minimal clinical guidelines to inform care pathways and the use of endoscopy, including (diagnostic and therapeutic yields), interventional radiology and surgery are poorly defined. As a result, there is potential for wide variation in practice and clinical outcomes. The UK Lower Gastrointestinal Bleeding Audit is a large nationwide audit of adult patients acutely admitted with LGIB or those who develop LGIB while hospitalised for another reason. Consecutive, unselected presentations with LGIB will be enrolled prospectively over a 2-month period at the end of 2015 and detailed data will be collected on patient characteristics, comorbidities, use of anticoagulants, transfusion, timing and modalities of diagnostic and therapeutic procedures, clinical outcome, length of stay and mortality. These will be audited against predefined minimum standards of care for LGIB. It is anticipated that over 80% of all acute hospitals in England and some hospitals in Scotland, Wales and Northern Ireland will participate. Data will be collected on the availability and organisation of care, provision of diagnostic and therapeutic GI endoscopy, interventional radiology, surgery and transfusion protocols. This audit will be conducted as part of the national comparative audit programme of blood transfusion through collaboration with specialists in gastroenterology, surgery and interventional radiology. Individual reports will be provided to each participant site as well as an overall report and disseminated through specialist societies. Results will also be published in peer-reviewed journals. The study has been funded by National Health Services (NHS) Blood and Transplant and the Bowel Disease Research Foundation and endorsed by the Association of Coloproctology of Great Britain and Ireland. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Interactive videoconsultation is a feasible method for neurological in-patient assessment.

PubMed

Craig, J; Patterson, V; Russell, C; Wootton, R

2000-11-01

To evaluate the feasibility of interactive videoconsultation (IATV) as a means by which neurologists might assess patients admitted with neurological symptoms to hospitals distant from a neurological centre, we studied 25 unselected patients using interactive videoconsultation (IATV) and then validated the IATV diagnoses and management plans at a later face-to-face consultation. IATV consultation led to an eventual diagnosis in 23 out of 25 patients, with one diagnosis being changed and one remaining uncertain. The IATV management plans were felt to be appropriate for all patients in study. Twelve patients were able to be discharged from hospital on the same day as IATV on the advice of the neurologist. It is therefore practical to assess patients admitted with neurological symptoms to distant hospitals using IATV and this may result in more efficient use of in-patient resources.

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population.

PubMed

Brain, Keith L; Kay, Jonathan; Shine, Brian

2006-11-01

Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability. We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor. The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD.nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD.nNMT gave higher sensitivity and specificity than the tests for either substance alone. The test for nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.

Predictive Value of the Sequential Organ Failure Assessment Score for Mortality in a Contemporary Cardiac Intensive Care Unit Population.

PubMed

Jentzer, Jacob C; Bennett, Courtney; Wiley, Brandon M; Murphree, Dennis H; Keegan, Mark T; Gajic, Ognjen; Wright, R Scott; Barsness, Gregory W

2018-03-10

Optimal methods of mortality risk stratification in patients in the cardiac intensive care unit (CICU) remain uncertain. We evaluated the ability of the Sequential Organ Failure Assessment (SOFA) score to predict mortality in a large cohort of unselected patients in the CICU. Adult patients admitted to the CICU from January 1, 2007, to December 31, 2015, at a single tertiary care hospital were retrospectively reviewed. SOFA scores were calculated daily, and Acute Physiology and Chronic Health Evaluation (APACHE)-III and APACHE-IV scores were calculated on CICU day 1. Discrimination of hospital mortality was assessed using area under the receiver-operator characteristic curve values. We included 9961 patients, with a mean age of 67.5±15.2 years; all-cause hospital mortality was 9.0%. Day 1 SOFA score predicted hospital mortality, with an area under the receiver-operator characteristic curve value of 0.83; area under the receiver-operator characteristic curve values were similar for the APACHE-III score, and APACHE-IV predicted mortality ( P >0.05). Mean and maximum SOFA scores over multiple CICU days had greater discrimination for hospital mortality ( P <0.01). Patients with an increasing SOFA score from day 1 and day 2 had higher mortality. Patients with day 1 SOFA score <2 were at low risk of mortality. Increasing tertiles of day 1 SOFA score predicted higher long-term mortality ( P <0.001 by log-rank test). The day 1 SOFA score has good discrimination for short-term mortality in unselected patients in the CICU, which is comparable to APACHE-III and APACHE-IV. Advantages of the SOFA score over APACHE include simplicity, improved discrimination using serial scores, and prediction of long-term mortality. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Challenges of coronary angiography and intervention in patients previously treated by TAVI.

PubMed

Blumenstein, Johannes; Kim, Won-Keun; Liebetrau, Christoph; Gaede, Luise; Kempfert, Joerg; Walther, Thomas; Hamm, Christian; Möllmann, Helge

2015-08-01

Since the beginning of the transcatheter aortic valve implantation (TAVI) era, many prosthetic valves have entered clinical practice. TAVI prostheses differ regarding stent design and some may potentially interfere with diagnostic or interventional catheters. The aim of our analysis was to evaluate the feasibility of coronary angiography (CA) or percutaneous coronary intervention (PCI) in patients with prior TAVI. From 2011 to 2014, 1,000 patients were treated by TAVI at our center using eight different valve prostheses (Symetis ACURATE TA and ACURATE TF; Medtronic CoreValve and Engager; JenaValve, SJM Portico; Edwards Lifesciences SAPIEN and SAPIEN XT). In this analysis, all patients were included who underwent either CA or PCI after TAVI. CA or PCI were rated as fully feasible when coronary ostia could be fully intubated, partially feasible when coronary arteries could be displayed only unselectively or unfeasible when coronary arteries could not be displayed. A total of 35 patients underwent CA/PCI after TAVI at our hospital. In all patients with valves implanted in a subcoronary position (SAPIEN n = 19; JenaValve n = 1), selective intubation was feasible using standard catheters. Out of 15 patients with valve types that are placed over the coronary ostia (CoreValve n = 10, ACURATE n = 4, Portico n = 1), selective intubation of coronary arteries was not possible in 9 cases, even with the use of different diagnostic catheters. Full accessibility was possible only in 3 cases. In 2 cases, display of the right CA was only feasible using unselective aortography. In 1 case, coronary arteries could not be displayed at all immediately after a valve-in-valve procedure. CA or PCI after TAVI is usually feasible. Devices that are placed in a partially supracoronary position, however, can interfere with diagnostic or guiding catheters and impede straightforward intervention, especially when the prosthesis is not implanted in the correct position.

EGFR Amplification as a Target in Gastroesophageal Adenocarcinoma: Do Anti-EGFR Therapies Deserve a Second Chance?

PubMed

Strickler, John H

2018-06-01

Anti-EGFR therapies have failed to improve survival for unselected patients with metastatic gastroesophageal cancer, but in a subset of patients, EGFR amplification may predict treatment benefit. Maron and colleagues report the clinical activity of anti-EGFR therapies in a cohort of patients with EGFR -amplified metastatic gastroesophageal cancer and utilize serial blood and tumor tissue collection to identify molecular drivers of treatment sensitivity and resistance. Their insights offer a path to overcome technical limitations associated with EGFR amplification and facilitate molecularly targeted therapeutic strategies. Cancer Discov; 8(6); 679-81. ©2018 AACR See related article by Maron et al., p. 696 . ©2018 American Association for Cancer Research.

Propranolol reduces the anxiety associated with day case surgery.

PubMed

Mealy, K; Ngeh, N; Gillen, P; Fitzpatrick, G; Keane, F B; Tanner, A

1996-01-01

To find out if propranolol, a non-cardioselective beta-blocker, can reduce the anxiety associated with day case surgery. Prospective randomized double blind trial. University hospital, Ireland. An unselected group of 53 patients undergoing day case surgery. Subjects randomised to receive either propranolol (10 mg) or placebo on the morning of operation. Blood pressure; pulse, anxiety, pain score and patient satisfaction. Mean (SD) Hospital Anxiety and Depression score was significantly lower in the propranolol group than in the control group (2.5 (0.7) compared with 4.6 (0.7), p < 0.0001) before discharge. A low dose of propranolol given on the morning of day case surgery significantly reduced patients' anxiety.

The consequences of balanced harvesting of fish communities

PubMed Central

Jacobsen, Nis S.; Gislason, Henrik; Andersen, Ken H.

2014-01-01

Balanced harvesting, where species or individuals are exploited in accordance with their productivity, has been proposed as a way to minimize the effects of fishing on marine fish communities and ecosystems. This calls for a thorough examination of the consequences balanced harvesting has on fish community structure and yield. We use a size- and trait-based model that resolves individual interactions through competition and predation to compare balanced harvesting with traditional selective harvesting, which protects juvenile fish from fishing. Four different exploitation patterns, generated by combining selective or unselective harvesting with balanced or unbalanced fishing, are compared. We find that unselective balanced fishing, where individuals are exploited in proportion to their productivity, produces a slightly larger total maximum sustainable yield than the other exploitation patterns and, for a given yield, the least change in the relative biomass composition of the fish community. Because fishing reduces competition, predation and cannibalism within the community, the total maximum sustainable yield is achieved at high exploitation rates. The yield from unselective balanced fishing is dominated by small individuals, whereas selective fishing produces a much higher proportion of large individuals in the yield. Although unselective balanced fishing is predicted to produce the highest total maximum sustainable yield and the lowest impact on trophic structure, it is effectively a fishery predominantly targeting small forage fish. PMID:24307676

Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

PubMed Central

van den Broek, Alexandra J; de Ruiter, Karen; van 't Veer, Laura J; Tollenaar, Rob A E M; van Leeuwen, Flora E; Verhoef, Senno; Schmidt, Marjanka K

2015-01-01

In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974–2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a ‘triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria. PMID:25138101

Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study

PubMed Central

2010-01-01

Introduction The Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff. Methods In this prospective observational study, scoring of GCS and FOUR score was performed by neurologists and ICU staff on 267 consecutive patients admitted to intensive care. Results In a total of 437 pair wise ratings the exact inter-rater agreement for the GCS was 71%, and for the FOUR score 82% (P = 0.0016); the inter-rater agreement within a range of ± 1 score point for the GCS was 90%, and for the FOUR score 92% (P = ns.). The exact inter-rater agreement among neurologists was superior to that among ICU staff for the FOUR score (87% vs. 79%, P = 0.04) but not for the GCS (73% vs. 73%). Neurologists and ICU staff did not significantly differ in the inter-rater agreement within a range of ± 1 score point for both GCS (88% vs. 93%) and the FOUR score (91% vs. 88%). Conclusions The FOUR score performed better than the GCS for exact inter-rater agreement, but not for the clinically more relevant agreement within the range of ± 1 score point. Though neurologists outperformed ICU staff with regard to exact inter-rater agreement, the inter-rater agreement of ICU staff within the clinically more relevant range of ± 1 score point equalled that of the neurologists. The small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in intensive care. PMID:20398274

Utility of Liquid Biopsy by Improved PNA-LNA PCR Clamp Method for Detecting EGFR Mutation at Initial Diagnosis of Non-Small-Cell Lung Cancer: Observational Study of 190 Consecutive Cases in Clinical Practice.

PubMed

Ito, Kentaro; Suzuki, Yuta; Saiki, Haruko; Sakaguchi, Tadashi; Hayashi, Kosuke; Nishii, Yoichi; Watanabe, Fumiaki; Hataji, Osamu

2018-03-01

The clinical benefit of liquid biopsy for unselected patients at initial diagnosis has thus far been unclear. We aimed to evaluate the utility of liquid biopsy at initial diagnosis, as well as the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) based on liquid biopsy results in clinical practice, using the improved peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp method. We routinely performed liquid biopsy using the improved PNA-LNA PCR clamp method for all patients diagnosed with non-small-cell lung cancer (NSCLC) between June 2015 and October 2016. We retrospectively evaluated the reliability of liquid biopsy based either on clinical stage or between sensitizing EGFR mutation and T790M mutation, and the clinical benefit of EGFR-TKI based on the liquid biopsy results in practice. A total of 244 patients underwent liquid biopsies, with 168 patients tested at diagnosis and 22 tested for T790M after pretreatment of EGFR-TKI. For detecting a sensitizing EGFR mutation, the sensitivity, specificity, positive predictive value, and negative predictive value were 72.7%, 100%, 100%, and 93.7% in the group with advanced-stage NSCLC and 0, 100%, not evaluable, and 70.5% in the group with early-stage NSCLC. The positive predictive value and negative predictive value for T790M were 33.3% and 55.6%, respectively. Fourteen patients in the liquid-positive group and 16 patients in the tissue-positive group received EGFR-TKI. The objective response rates of first- and second-generation EGFR-TKI for the liquid-positive and tissue-positive groups were 90.0% and 90.9%, respectively. There was no significant difference in median progression-free survival between the liquid-positive and tissue-positive groups (P = .839). Patients with early-stage NSCLC should not be candidates for this liquid biopsy method. We recommend tissue biopsy as the preferred initial method of molecular analysis, with the exception of patients who are T790M positive or patients who are unable to tolerate invasive biopsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Cell-based strategies to manage leukemia relapse: efficacy and feasibility of immunotherapy approaches.

PubMed

Rambaldi, A; Biagi, E; Bonini, C; Biondi, A; Introna, M

2015-01-01

When treatment fails, the clinical outcome of acute leukemia patients is usually very poor, particularly when failure occurs after transplantation. A second allogeneic stem cell transplant could be envisaged as an effective and feasible salvage option in younger patients having a late relapse and an available donor. Unmanipulated or minimally manipulated donor T cells may also be effective in a minority of patients but the main limit remains the induction of severe graft-versus-host disease. This clinical complication has brought about a huge research effort that led to the development of leukemia-specific T-cell therapy aiming at the direct recognition of leukemia-specific rather than minor histocompatibility antigens. Despite a great scientific interest, the clinical feasibility of such an approach has proven to be quite problematic. To overcome this limitation, more research has moved toward the choice of targeting commonly expressed hematopoietic specific antigens by the genetic modification of unselected T cells. The best example of this is represented by the anti-CD19 chimeric antigen receptor (CD19.CAR) T cells. As a possible alternative to the genetic manipulation of unselected T cells, specific T-cell subpopulations with in vivo favorable homing and long-term survival properties have been genetically modified by CAR molecules. Finally, the use of naturally cytotoxic effector cells such as natural killer and cytokine-induced killer cells has been proposed in several clinical trials. The clinical development of these latter cells could also be further expanded by additional genetic modifications using the CAR technology.

High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial.

PubMed

Azoulay, Elie; Lemiale, Virginie; Mokart, Djamel; Nseir, Saad; Argaud, Laurent; Pène, Frédéric; Kontar, Loay; Bruneel, Fabrice; Klouche, Kada; Barbier, François; Reignier, Jean; Stoclin, Anabelle; Louis, Guillaume; Constantin, Jean-Michel; Mayaux, Julien; Wallet, Florent; Kouatchet, Achille; Peigne, Vincent; Perez, Pierre; Girault, Christophe; Jaber, Samir; Oziel, Johanna; Nyunga, Martine; Terzi, Nicolas; Bouadma, Lila; Lebert, Christine; Lautrette, Alexandre; Bigé, Naike; Raphalen, Jean-Herlé; Papazian, Laurent; Rabbat, Antoine; Darmon, Michael; Chevret, Sylvie; Demoule, Alexandre

2018-03-05

Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO 2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated. This is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO 2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included). The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections. Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient. The HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population. ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016.

Recurrent ischemia across the spectrum of acute coronary syndromes: prevalence and prognostic significance of (re-)infarction and ST-segment changes in a large contemporary registry.

PubMed

Yan, Andrew T; Steg, Philippe Gabriel; Fitzgerald, Gordon; Feldman, Laurent J; Eagle, Kim A; Gore, Joel M; Anderson, Frederick A; López-Sendón, Jose; Gurfinkel, Enrique P; Brieger, David; Goodman, Shaun G

2010-11-05

There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era. The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms. Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003). Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom Study.

PubMed

Burisch, Johan; Vardi, Hillel; Pedersen, Natalia; Brinar, Marko; Cukovic-Cavka, Silvja; Kaimakliotis, Ioannis; Duricova, Dana; Bortlik, Martin; Shonová, Olga; Vind, Ida; Avnstrøm, Søren; Thorsgaard, Niels; Krabbe, Susanne; Andersen, Vibeke; Dahlerup, Jens F; Kjeldsen, Jens; Salupere, Riina; Olsen, Jónger; Nielsen, Kári R; Manninen, Pia; Collin, Pekka; Katsanos, Konstantinnos H; Tsianos, Epameinondas V; Ladefoged, Karin; Lakatos, Laszlo; Bailey, Yvonne; OʼMorain, Colm; Schwartz, Doron; Lupinacci, Guido; De Padova, Angelo; Jonaitis, Laimas; Kupcinskas, Limas; Turcan, Svetlana; Barros, Louisa; Magro, Fernando; Lazar, Daniela; Goldis, Adrian; Nikulina, Inna; Belousova, Elena; Fernandez, Alberto; Pineda, Juan R; Almer, Sven; Halfvarson, Jonas; Tsai, Her-Hsin; Sebastian, Shaji; Friger, Michael; Greenberg, Dan; Lakatos, Peter L; Langholz, Ebbe; Odes, Selwyn; Munkholm, Pia

2015-01-01

No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe. The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (€) using the Danish Health Costs Register. One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was €5,408,174 (investigations: €2,042,990 [38%], surgery: €1,427,648 [26%], biologicals: €781,089 [14%], and standard treatment: €1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations €1803 (€2160) (P = 0.44), surgery €11,489 (€13,973) (P = 0.14), standard treatment €1027 (€824) (P = 0.51), and biologicals €7376 (€8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations €1189 ( €1518) (P < 0.01), surgery €18,414 ( €12,395) (P = 0.18), standard treatment €896 ( €798) (P < 0.05), and biologicals €5681 ( €72) (P = 0.51). In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.

Polymorphisms in nonhomologous end-joining genes associated with breast cancer risk and chromosomal radiosensitivity.

PubMed

Willems, Petra; Claes, Kathleen; Baeyens, Ans; Vandersickel, Veerle; Werbrouck, Joke; De Ruyck, Kim; Poppe, Bruce; Van den Broecke, Rudy; Makar, Amin; Marras, Emanuela; Perletti, Gianpaolo; Thierens, Hubert; Vral, Anne

2008-02-01

As enhanced chromosomal radiosensitivity (CRS) results from non- or misrepaired double strand breaks (DSBs) and is a hallmark for breast cancer and single nucleotide polymorphisms (SNPs) in DSB repair genes, such as non homologous end-joining (NHEJ) genes, could be involved in CRS and genetic predisposition to breast cancer. In this study, we investigated the association of five SNPs in three different NHEJ genes with breast cancer in a population-based case-control setting. The total patient population composed of a selected group of patients with a family history of the disease and an unselected group, consisting mainly of sporadic cases. SNP analysis showed that the c.2099-2408G>A SNP (XRCC5Ku80) [corrected] has a significant, positive odds ratio (OR) of 2.81 (95% confidence interval (CI): 1.30-6.05) for the heterozygous (He) and homozygous variant (HV) genotypes in the selected patient group. For the c.-1310 C>G SNP (XRCC6Ku70)[corrected] a significant OR of 1.85 (95%CI: 1.01-3.41) was found for the He genotype in the unselected patient group. On the contrary, the HV genotype of c.1781G>T (XRCC6Ku70) [corrected] displays a significant, negative OR of 0.43 (95%CI: 0.18-0.99) in the total patient population. The He+HV genotypes of the c.2099-2408G>A SNP (XRCC5Ku80) [corrected] also showed high and significant ORs in the group of "radiosensitive," familial breast cancer patients. In conclusion, our results provide preliminary evidence that the variant allele of c.-1310C>G (XRCC6Ku70) [corrected]and c.2099-2408G>A (XRCC5Ku80) [corrected] are risk alleles for breast cancer as well as CRS. The HV genotype of c.1781G>T (XRCC6Ku70) [corrected] on the contrary, seems to protect against breast cancer and ionizing radiation induced micronuclei. (c) 2007 Wiley-Liss, Inc.

Anti-tumour activity of platinum compounds in advanced prostate cancer-a systematic literature review.

PubMed

Hager, S; Ackermann, C J; Joerger, M; Gillessen, S; Omlin, A

2016-06-01

For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. To systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients. PubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers. A total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%-40% for objective response and 20%-70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied. Platinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Significance of Large Vessel Intracranial Occlusion Causing Acute Ischemic Stroke and TIA

PubMed Central

Smith, Wade S.; Lev, Michael H.; English, Joey D.; Camargo, Erica C.; Chou, Maggie; Johnston, S. Claiborne; Gonzalez, Gilberto; Schaefer, Pamela W.; Dillon, William P.; Koroshetz, Walter J.; Furie, Karen L.

2009-01-01

Background: Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries- likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data has been reported on a cohort of unselected stroke and TIA patients, the clinical impact of LVO has been difficult to quantify. Methods: The STOP-Stroke Study is a prospective imaging-based study of stroke outcomes performed at two academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multi-modality CT/CTA were approached for consent for collection of clinical data and 6 month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin scores (mRS) were collected and combined with blinded interpretation of the CTA data. The odds ratio (OR) of each variable including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality was calculated using univariate and multivariate logistic regression. Results: Over a 33 month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as TIA. Among stroke patients, 267 (46%) had LVO accounting for the stroke and 13 (13%) of TIA patients had LVO accounting for TIA symptoms. LVO predicted six-month mortality (OR 4.5; 95% CI 2.7-7.3; p<0.001). Six-month good outcome (mRS≤ 2) was negatively predicted by LVO (0.33; 0.24-0.45; p<0.001). Based on multivariate analysis, the presence of basilar and internal carotid terminus occlusions, in addition to NIHSS and age, independently predicted outcome. Conclusion: Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months. PMID:19834014

Deficit in automatic sound-change detection may underlie some music perception deficits after acute hemispheric stroke.

PubMed

Kohlmetz, C; Altenmüller, E; Schuppert, M; Wieringa, B M; Münte, T F

2001-01-01

Music perception deficits following acute neurological damage are thought to be rare. By a newly devised test battery of music-perception skills, however, we were able to identify among a group of 12 patients with acute hemispheric stroke six patients with music perception deficits (amusia) while six others had no such deficits. In addition we recorded event-related brain potentials (ERPs) in a passive listening task with frequent standard and infrequent pitch deviants designed to elicit the mismatch negativity (MMN). The MMN in the patients with amusia was grossly reduced, while the non-amusic patients and control subjects had MMNs of equal size. These data show that amusia is quite common in unselected stroke patients. The MMN reduction suggests that amusia is related to unspecific automatic stimulus classification deficits in these patients.

Precancerous lesions of the cervix uteri in infertile women.

PubMed Central

Holst, N; Abyholm, T

1983-01-01

A study of 318 patients with tubal infertility and a control group of 200 unselected infertile women yielded 14 (4.4%) and 1 (0.5%), respectively, with precancerous lesions of the cervix uteri. The one patient in the control group with severe dysplasia was later shown to have tubal infertility. The overall incidence of premalignant lesions of the cervix uteri as reported to the National Cancer Registry of Norway was 0.1% for the age group and period studied. Women with tubal infertility represent a small but comparatively high risk group for the development of precancerous lesions of the cervix uteri. PMID:6412931

Brown Nail-bed Arcs and Chronic Renal Disease

PubMed Central

Stewart, W. K.; Raffle, E. J.

1972-01-01

A brown arc affecting the distal part of the fingernail-bed, just proximal to the point of separation of the nail from its bed, has been found in 12 out of 34 patients with chronic renal disease (35%) compared with an incidence of less than 2% in a series of unselected patients. It represents a distinctive form of pigmentation, possibly due to lipochromes. No decisive association could be found between the presence or absence of the pigmented nail arc and the level of impaired renal function. Nevertheless it seems that renal disease predisposes towards the development of brown nail arcs. Imagesp786-a PMID:5014252

Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer

PubMed Central

Ray-Coquard, Isabelle; Selle, Frederic; Poveda, Andrés M.; Cibula, David; Hirte, Hal; Hilpert, Felix; Raspagliesi, Francesco; Gladieff, Laurence; Harter, Philipp; Siena, Salvatore; del Campo, Josep Maria; Tabah-Fisch, Isabelle; Pearlberg, Joseph; Moyo, Victor; Riahi, Kaveh; Nering, Rachel; Kubasek, William; Adiwijaya, Bambang; Czibere, Akos; Naumann, R. Wendel; Coleman, Robert L.; Vergote, Ignace; MacBeath, Gavin; Pujade-Lauraine, Eric

2016-01-01

Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) –mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels. PMID:27998236

Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer.

PubMed

Liu, Joyce F; Ray-Coquard, Isabelle; Selle, Frederic; Poveda, Andrés M; Cibula, David; Hirte, Hal; Hilpert, Felix; Raspagliesi, Francesco; Gladieff, Laurence; Harter, Philipp; Siena, Salvatore; Del Campo, Josep Maria; Tabah-Fisch, Isabelle; Pearlberg, Joseph; Moyo, Victor; Riahi, Kaveh; Nering, Rachel; Kubasek, William; Adiwijaya, Bambang; Czibere, Akos; Naumann, R Wendel; Coleman, Robert L; Vergote, Ignace; MacBeath, Gavin; Pujade-Lauraine, Eric

2016-12-20

Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels.

How do medical students engaging in elective courses on acupuncture and homeopathy differ from unselected students? A survey.

PubMed

Jocham, Alexandra; Kriston, Levente; Berberat, Pascal O; Schneider, Antonius; Linde, Klaus

2017-03-09

We aimed to investigate whether students at German medical schools participating in elective courses on acupuncture and homeopathy differ from an unselected group of students regarding attitudes and personality traits. Elective courses on acupuncture and homeopathy in the academic half-year 2013/14 all over Germany were identified and participants invited to fill in a questionnaire including nineteen questions on attitudes towards Complementary and Alternative Medicine (CAM), orientation towards science, care and status orientation, and a short validated instrument (Big-Five-Inventory-10) to measure personality traits (extraversion, neuroticism, openness, conscientiousness, and agreeableness). Participants of a mandatory family medicine course at one university served as unselected control group. Two hundred twenty and 113 students from elective courses on acupuncture and homeopathy, respectively, and 315 control students participated (response rate 93%). Students participating in elective courses had much more positive attitudes towards CAM, somewhat lower science and status orientation, and somewhat higher care orientation than control group students (all p-values for three-group comparisons < 0.001). There were no differences between the three groups regarding personality traits with the exception of lower values for agreeableness in controls (p = 0.009). The findings of this study show that attitudes of students participating in elective courses on acupuncture or homeopathy at German medical schools differ to a considerable degree from the attitudes of unselected students.

Prognostic impact of CXCL16 and CXCR6 in non-small cell lung cancer: combined high CXCL16 expression in tumor stroma and cancer cells yields improved survival.

PubMed

Hald, Sigurd M; Kiselev, Yury; Al-Saad, Samer; Richardsen, Elin; Johannessen, Charles; Eilertsen, Marte; Kilvaer, Thomas K; Al-Shibli, Khalid; Andersen, Sigve; Busund, Lill-Tove; Bremnes, Roy M; Donnem, Tom

2015-05-29

The chemokine CXCL16 and its receptor CXCR6 are expressed by a variety of immune cells and have been shown to influence angiogenesis. The expression of CXCR6 and CXCL16 has been examined in numerous human cancers; however no studies have yet investigated their influence on prognosis in non-small cell lung cancer (NSCLC). We aimed to explore their prognostic significance in NSCLC, in addition to examining associations with previously investigated markers. Resected tumor tissue from 335 consecutive unselected stage I-IIIA NSCLC patients (1990-2005) were collected. Immunohistochemistry was used to evaluate the expression of CXCR6 and CXCL16 on tissue microarrays. In vitro, NSCLC cells (NCI-H460, A549 cells) were transfected with CXCL16 siRNA to examine effects on proliferation. In univariate analysis, ↑ stromal cell CXCL16 expression was a significant positive prognostic factor (P = 0.016). CXCR6 was expressed in cancer cells, but did not show any prognostic impact. In the multivariate analysis, combined ↑cancer, and ↑stromal cell CXCL16 expression was an independent positive prognostic factor when compared to ↓stromal and ↓cancer cell expression (HR: 0.42; 95 % CI: 0.20-0.88; P = 0.022). Knockdown of CXCL16 by siRNA resulted in accelerated proliferation of NSCLC cell lines. We have shown that combined ↑cancer and ↑stromal cell CXCL16 expression is an independent positive prognostic factor in NSCLC. Further studies are warranted to elucidate the biological mechanism underlying this finding.

An acute stroke evaluation app: a practice improvement project.

PubMed

Rubin, Mark N; Fugate, Jennifer E; Barrett, Kevin M; Rabinstein, Alejandro A; Flemming, Kelly D

2015-04-01

A point-of-care workflow checklist in the form of an iOS (iPhone Operating System) app for use by stroke providers was introduced with the objective of standardizing acute stroke evaluation and documentation at 2 affiliated academic medical centers. Providers used the app in unselected, consecutive patients undergoing acute stroke evaluation in an emergency department or hospital setting between August 2012 and January 2013 and August 2013 and February 2014. Satisfaction surveys were prospectively collected pre- and postintervention from residents, staff neurologists, and clinical data specialists. Residents (20 preintervention and 16 postintervention), staff neurologists (6 pre and 5 post), and clinical data specialists (4 pre and 4 post) participated in this study. All 16 (100%) residents had increased satisfaction with their ability to perform an acute stroke evaluation postintervention but only 9 (56%) of 16 felt the app was more help than hindrance. Historical controls aligned with preintervention results. Staff neurologists conveyed increased satisfaction with resident presentations and decision making when compared to preintervention surveys. Stroke clinical data specialists estimated a 50% decrease in data abstraction when the app data were used in the clinical note. Concomitant effect on door-to-needle (DTN) time at 1 site, although not a primary study measure, was also evaluated. At that 1 center, the mean DTN time decreased by 16 minutes when compared to the corresponding months from the year prior. The point-of-care acute stroke workflow checklist app may assist trainees in presenting findings in a standardized manner and reduce data abstraction time. The app may help reduce DTN time, but this requires further study.

Postabortal endometritis and isolation of Chlamydia trachomatis.

PubMed

Barbacci, M B; Spence, M R; Kappus, E W; Burkman, R C; Rao, L; Quinn, T C

1986-11-01

A prospective study of 505 unselected women presenting for induced abortion was undertaken to determine the prevalence of Chlamydia trachomatis and to determine if cervical isolation of C trachomatis before abortion increases the risk of postabortal endometritis. A comparison of direct fluorescent antibody (slide) test with tissue culture for diagnosing C trachomatis infection also was evaluated in this population. C trachomatis was identified by culture in 89 patients (17.6%) and by direct slide test in 85 patients (16.8%). Six of 17 patients with postabortal endometritis were culture positive for C trachomatis, with a significant correlation between C trachomatis infection and development of endometritis observed (P less than .05). These data suggest C trachomatis may play an important role in postabortal endometritis.

Comparing observed and predicted mortality among ICUs using different prognostic systems: why do performance assessments differ?

PubMed

Kramer, Andrew A; Higgins, Thomas L; Zimmerman, Jack E

2015-02-01

To compare ICU performance using standardized mortality ratios generated by the Acute Physiology and Chronic Health Evaluation IVa and a National Quality Forum-endorsed methodology and examine potential reasons for model-based standardized mortality ratio differences. Retrospective analysis of day 1 hospital mortality predictions at the ICU level using Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum models on the same patient cohort. Forty-seven ICUs at 36 U.S. hospitals from January 2008 to May 2013. Eighty-nine thousand three hundred fifty-three consecutive unselected ICU admissions. None. We assessed standardized mortality ratios for each ICU using data for patients eligible for Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum predictions in order to compare unit-level model performance, differences in ICU rankings, and how case-mix adjustment might explain standardized mortality ratio differences. Hospital mortality was 11.5%. Overall standardized mortality ratio was 0.89 using Acute Physiology and Chronic Health Evaluation IVa and 1.07 using National Quality Forum, the latter having a widely dispersed and multimodal standardized mortality ratio distribution. Model exclusion criteria eliminated mortality predictions for 10.6% of patients for Acute Physiology and Chronic Health Evaluation IVa and 27.9% for National Quality Forum. The two models agreed on the significance and direction of standardized mortality ratio only 45% of the time. Four ICUs had standardized mortality ratios significantly less than 1.0 using Acute Physiology and Chronic Health Evaluation IVa, but significantly greater than 1.0 using National Quality Forum. Two ICUs had standardized mortality ratios exceeding 1.75 using National Quality Forum, but nonsignificant performance using Acute Physiology and Chronic Health Evaluation IVa. Stratification by patient and institutional characteristics indicated that units caring for more severely ill patients and those with a higher percentage of patients on mechanical ventilation had the most discordant standardized mortality ratios between the two predictive models. Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum models yield different ICU performance assessments due to differences in case-mix adjustment. Given the growing role of outcomes in driving prospective payment patient referral and public reporting, performance should be assessed by models with fewer exclusions, superior accuracy, and better case-mix adjustment.

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population

PubMed Central

Brain, Keith L.; Kay, Jonathan; Shine, Brian

2009-01-01

Background Despite the rarity of pheochromocytoma, the dangers of uncontrolled severe hypertension and the very effective surgical treatment of this condition mean that diagnosis is important. Urinary or plasma catecholamines or catecholamine-derivatives are commonly used to screen for pheochromocytomas prior to imaging. This study investigates whether derived measures obtained from 24-hour urinary metanephrine results, patient age and sex can better predict tumors in populations with a low pre-test probability. Methods This study takes a pragmatic approach by retrospectively studying the outcomes of an unselected population referred for urinary metanephrine testing (1819 patients) to a tertiary hospital laboratory, and investigates the usefulness of some simple derivative measures for detecting pheochromocytoma. Urinary 24-hour excretion of metanephrine, normetanephrine and 3-methoxytyramine were normalized by dividing by an age- and sex- specific reference range. The ability of products of these normalized measures to predict pheochromocytomas was assessed, compared to a gold standard of biopsy-confirmed tumor. Results The normalized product of urinary metanephrine and normetanephrine excretion (nMAD.nNMT) proved to be a highly sensitive (100%) and specific (99.1%) measure yielding a positive predictive value 82%. Receiver-operator characteristic curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. nMAD.nNMT gave higher sensitivity and specificity than either test alone. Conclusion We suggest that nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pre-test probability. PMID:16990424

Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland.

PubMed

Sobczak, K; Kozłowski, P; Napierała, M; Czarny, J; Woźniak, M; Kapuścińska, M; Lośko, M; Koziczak, M; Jasińska, A; Powierska, J; Braczkowski, R; Breborowicz, J; Godlewski, D; Mackiewicz, A; Krzyzosiak, W

1997-10-09

Three different novel BRCA1 mutations, five independent cases of the same 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identified among 122 Polish women with positive, in most cases moderate family history of breast and/or ovarian cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in intron-20 were first found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT-PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.

Urine output on ICU entry is associated with hospital mortality in unselected critically ill patients.

PubMed

Zhang, Zhongheng; Xu, Xiao; Ni, Hongying; Deng, Hongsheng

2014-02-01

Urine output (UO) is routinely measured in the intensive care unit (ICU) but its prognostic value remains debated. The study aimed to investigate the association between day 1 UO and hospital mortality. Clinical data were abstracted from the Multiparameter Intelligent Monitoring in Intensive Care II (version 2.6) database. UO was recorded for the first 24 h after ICU entry, and was classified into three categories: UO >0.5, 0.3-0.5 and ≤0.3 ml/kg per hour. The primary endpoint was the hospital mortality. Four models were built to adjust for the hazards ratio of mortality. A total of 21,207 unselected ICU patients including 2,401 non-survivors and 18,806 survivors were included (mortality rate 11.3 %). Mortality rate increased progressively across UO categories: >0.5 (7.67 %), 0.3-0.5 (11.27 %) and ≤0.3 ml/kg/h (18.29 %), and this relationship remained statistically significant after rigorous control of confounding factors with the Cox proportional hazards regression model. With UO >0.5 as the referent group, the hazards ratios for UO 0.3-0.5 and UO ≤0.3 were 1.41 (95 % CI 1.29-1.54) and 1.52 (95 % CI 1.38-1.67), respectively. UO obtained on ICU entry is an independent predictor of mortality irrespective of diuretic use. It would be interesting to examine whether strategies to increase UO would improve clinical outcome.

Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma

PubMed Central

Johannesen, Tom B⊘rge; Berner, Aasmund; Haugland, Hans Kristian; Bjerkehagen, Bodil; B⊘hler, Per J.; Bruland, Øyvind S.

2015-01-01

Abstract Background This study describes time-trends on epidemiology, subtypes and histopathological entities of osteosarcoma (OS) in a nationwide and unselected cohort of OS patients in Norway between 1975 and 2009. Few nationwide studies are published, and we still have particularly limited knowledge regarding patients not included in clinical trials comprising about half of the OS population. Method Histologically verified skeletal OS for all subgroups were included, resulting in 473 eligible cases from a total of 702 evaluated patients. To ensure completeness, the present cohort was based on all cases reported to the Norwegian Cancer Registry, complemented with data from all Norwegian hospitals involved in sarcoma management. Survival analyses were performed with overall and sarcoma-specific survival as endpoints. Results Mean annual age-standard incidence amounted to about 3.8 per million in male and 2.8 per million in female with no clear time-trends. The male to female ratio was 1.4. Peak incidence was observed in the second decade for both genders. Conventional OS comprised 71.2% of all cases, while low grade OS represented 10.4% and telangiectatic OS only 1.3%. The most common primary site of OS was femur and tibia, respectively. The axial to appendicular ratio increased with the age. The overall 10-year survival did increase from about 30% during the late 1970s to around 50% 20 years later, with no subsequent improvement during the last two decades. Axial tumours, age above 40 years and overt metastatic disease at time of diagnosis were all negative prognostic factors. Conclusion No improvement in the overall survival for OS since the 1990s was documented. The survival rates are still poor for elderly people, patients with axial disease and in the primary metastatic setting. The average incidence rate of skeletal OS in Norway was in line with international figures. PMID:24957555

Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma.

PubMed

Berner, Kjetil; Johannesen, Tom Børge; Berner, Aasmund; Haugland, Hans Kristian; Bjerkehagen, Bodil; Bøhler, Per J; Bruland, Øyvind S

2015-01-01

This study describes time-trends on epidemiology, subtypes and histopathological entities of osteosarcoma (OS) in a nationwide and unselected cohort of OS patients in Norway between 1975 and 2009. Few nationwide studies are published, and we still have particularly limited knowledge regarding patients not included in clinical trials comprising about half of the OS population. Histologically verified skeletal OS for all subgroups were included, resulting in 473 eligible cases from a total of 702 evaluated patients. To ensure completeness, the present cohort was based on all cases reported to the Norwegian Cancer Registry, complemented with data from all Norwegian hospitals involved in sarcoma management. Survival analyses were performed with overall and sarcoma-specific survival as endpoints. Mean annual age-standard incidence amounted to about 3.8 per million in male and 2.8 per million in female with no clear time-trends. The male to female ratio was 1.4. Peak incidence was observed in the second decade for both genders. Conventional OS comprised 71.2% of all cases, while low grade OS represented 10.4% and telangiectatic OS only 1.3%. The most common primary site of OS was femur and tibia, respectively. The axial to appendicular ratio increased with the age. The overall 10-year survival did increase from about 30% during the late 1970s to around 50% 20 years later, with no subsequent improvement during the last two decades. Axial tumours, age above 40 years and overt metastatic disease at time of diagnosis were all negative prognostic factors. No improvement in the overall survival for OS since the 1990s was documented. The survival rates are still poor for elderly people, patients with axial disease and in the primary metastatic setting. The average incidence rate of skeletal OS in Norway was in line with international figures.

Lasting impact of an implemented self-management programme for people with type 2 diabetes referred from primary care: a one-group, before-after design.

PubMed

Fløde, Mari; Iversen, Marjolein M; Aarflot, Morten; Haltbakk, Johannes

2017-12-01

Research interventions in uniform clinical settings and in patients fulfilling well-defined inclusion criteria might show a more pronounced effect than implementing the same intervention in existing practice. Diabetes Self-Management Education (DSME) is complex, and should be assessed in existing practice as it is an intervention widely implemented. To examine the impact of an established group-based DSME in unselected people with type 2 diabetes referred from primary care. A one-group, before-after design was used for assessments before, immediately after, and 3 months after participation in a group-based DSME programme conducted at two Learning and Mastering Centres in Norway between November 2013 and June 2014. Participants completed a questionnaire before (n = 115), immediately after (n = 95) and 3 months after (n = 42) the DSME programme. Primary outcome measure was diabetes knowledge (Michigan Diabetes Knowledge Test). Also patient activation (Patient Activation Measure [PAM]) and self-efficacy (General Self-Efficacy scale [GSE]) were measured. Changes in outcome measures were analysed using paired t-tests for normally distributed data and Wilcoxon signed-rank test for skewed data. Mean knowledge improved significantly from baseline (p < 0.001). Changes persisted at the 3-month assessment. Mean PAM scores improved significantly from baseline (p < 0.001), and changes persisted for 3 months. Mean GSE scores improved from baseline (p = 0.022) and persisted for 3 months. However, when results were stratified for participants who responded at all three time points, GSE showed no change during the study period. The complexity self-management in the individual is challenging to reflect in DSME. This implemented DSME programme for people with type 2 diabetes improved levels of diabetes knowledge and patient activation, persisting for at least 3 months. Hence, the DSME programme appears to be robust beyond standardised research settings, in educating unselected diabetes patients referred from primary care. © 2017 Nordic College of Caring Science.

What is the evidence base to guide surgical treatment of infected hip prostheses? systematic review of longitudinal studies in unselected patients

PubMed Central

2012-01-01

Background Prosthetic joint infection is an uncommon but serious complication of hip replacement. There are two main surgical treatment options, with the choice largely based on the preference of the surgeon. Evidence is required regarding the comparative effectiveness of one-stage and two-stage revision to prevent reinfection after prosthetic joint infection. Methods We conducted a systematic review to identify randomised controlled trials, systematic reviews and longitudinal studies in unselected patients with infection treated exclusively by one- or two-stage methods or by any method. The Embase, MEDLINE and Cochrane databases were searched up to March 2011. Reference lists were checked, and citations of key articles were identified by using the ISI Web of Science portal. Classification of studies and data extraction were performed independently by two reviewers. The outcome measure studied was reinfection within 2 years. Data were combined to produce pooled random-effects estimates using the Freeman-Tukey arc-sine transformation. Results We identified 62 relevant studies comprising 4,197 patients. Regardless of treatment, the overall rate of reinfection after any treatment was 10.1% (95% CI = 8.2 to 12.0). In 11 studies comprising 1,225 patients with infected hip prostheses who underwent exclusively one-stage revision, the rate of reinfection was 8.6% (95% CI = 4.5 to 13.9). After two-stage revision exclusively in 28 studies comprising 1,188 patients, the rate of reinfection was 10.2% (95% CI = 7.7 to 12.9). Conclusion Evidence of the relative effectiveness of one- and two-stage revision in preventing reinfection of hip prostheses is largely based on interpretation of longitudinal studies. There is no suggestion in the published studies that one- or two stage methods have different reinfection outcomes. Randomised trials are needed to establish optimum management strategies. PMID:22340795

Immunophenotypic analysis of adult patients with T-cell lymphoblastic lymphoma treated with hyper-CVAD.

PubMed

Kato, Harumi; Yamamoto, Kazuhito; Kodaira, Takeshi; Higuchi, Yusuke; Yamamoto, Hideyuki; Saito, Toko; Taji, Hirofumi; Yatabe, Yasushi; Nakamura, Shigeo; Kinoshita, Tomohiro

2018-03-01

Immunophenotype is an important prognostic factor for childhood and adult T-cell acute lymphoblastic leukemia. However, immunophenotypic data from adult patients with T-cell lymphoblastic lymphoma (T-LBL) are scarcely available. Subjects were unselected adult patients with T-LBL who were treated with intensive chemotherapy. Immunophenotyping of tumor cells was performed according to standard techniques. A total of eight patients with a median age of 31 years were analyzed who received hyper-CVAD treatment for LBL. Immunophenotypic analysis showed that the most common tumor type was cortical T-cell type [early T (n = 2), cortical T (n = 4), and medullary T (n = 2)]. Two patients diagnosed with early T-cell type had early disease progression. Assessment of T-cell differentiation stages in malignant T lymphoblasts would be important in choosing treatment strategies for adult patients with T-LBL.

Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for newborn screening.

PubMed

Kunz, Joachim B; Awad, Saida; Happich, Margit; Muckenthaler, Lena; Lindner, Martin; Gramer, Gwendolyn; Okun, Jürgen G; Hoffmann, Georg F; Bruckner, Thomas; Muckenthaler, Martina U; Kulozik, Andreas E

2016-02-01

Children with sickle cell disease (SCD) benefit from newborn screening, because life-threatening complications can be prevented by pre-symptomatic diagnosis. In Germany, the immigration of people from endemic countries is steadily growing. Comprehensive data about the epidemiology and prevalence of SCD in Germany are however lacking, and SCD is not included in the national newborn screening program. We provide data on the prevalence of SCD in a population from both urban and rural areas in Southwest Germany. Anonymized dried blood spots from 37,838 unselected newborns were analyzed by allele-specific PCR for the HbS mutation. Samples tested positive were subjected to Sanger sequencing of the entire β-globin coding sequence firstly to validate the screening and secondly to identify compound heterozygous SCD patients with other mutations of the β-globin gene. We identified 83 carriers of the sickle cell trait, three compound heterozygous SCD patients (two with sickle cell-β-thalassemia, one with sickle cell-Hb Tianshui) but no homozygous SCD patients. The novel molecular method and strategy for newborn screening for SCD presented here compares favorably in terms of sensitivity (1.0 for homozygous HbS, 0.996 for heterozygous HbS), specificity (0.996), practicability, and costs with conventional biochemical screening. Our results demonstrate a significant prevalence of SCD of approximately 1:12,000 in an unselected urban and rural population in Southwest Germany. Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany.

The Spectrum of Renal Allograft Failure

PubMed Central

Chand, Sourabh; Atkinson, David; Collins, Clare; Briggs, David; Ball, Simon; Sharif, Adnan; Skordilis, Kassiani; Vydianath, Bindu; Neil, Desley; Borrows, Richard

2016-01-01

Background Causes of “true” late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. Methods We evaluated all unselected graft failures from 2008–2014 (n = 171; 0–36 years post-transplantation) by contemporary classification of indication biopsies “proximate” to failure, DSA assessment, clinical and biochemical data. Results The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and ‘interstitial fibrosis with tubular atrophy’ without rejection, infection or recurrent disease (“IFTA”). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). Conclusion This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and individualised patient care. PMID:27649571

Circulating neural antibodies in unselected children with new-onset seizures.

PubMed

Garcia-Tarodo, Stephanie; Datta, Alexandre N; Ramelli, Gian P; Maréchal-Rouiller, Fabienne; Bien, Christian G; Korff, Christian M

2018-05-01

The role of autoimmunity and neural antibodies is increasingly recognized in different forms of seizures and epilepsy. Their prevalence in new-onset epilepsy has also recently been the focus of several clinical cohorts in the adult and pediatric population, with positive titers in 10-11% of cases. Our aim was to determine the seropositivity at the first seizure onset in a non-selective group of children. We conducted a prospective multicenter cohort study recruiting children aged 0-16 years with new-onset seizures presenting at the In- and Outpatient Pediatric Neurology Departments of three Children's Hospitals in Switzerland between September 2013 and April 2016. Neural antibodies were screened within the first 6 months of a first seizure and when positive, repeated at 1 month and 6 months follow-up. A total of 103 children were enrolled with a mean age at presentation of 5 years (range 1 day-15 years 9 months). The majority (n = 75) presented with generalized seizures and 6 had status epilepticus lasting > 30 min. At the time of onset, 55% of patients had fever, 24% required emergency seizure treatment and 27% hospitalization. Epilepsy was diagnosed at follow-up in 18%. No specific antibody was found. Serum antibodies against the VGKC complex, without binding to the specific antigens LGI1 and CASPR2, were found in two patients. Four patients harbored not otherwise characterized antibodies against mouse neuropil. Specific neural antibodies are rarely found in an unselected population of children that present with a first seizure. Applying an extensive neuronal antibody profile in a child with new-onset seizures does not appear to be justified. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

CHEK2 mutations and the risk of papillary thyroid cancer.

PubMed

Siołek, Monika; Cybulski, Cezary; Gąsior-Perczak, Danuta; Kowalik, Artur; Kozak-Klonowska, Beata; Kowalska, Aldona; Chłopek, Małgorzata; Kluźniak, Wojciech; Wokołorczyk, Dominika; Pałyga, Iwona; Walczyk, Agnieszka; Lizis-Kolus, Katarzyna; Sun, Ping; Lubiński, Jan; Narod, Steven A; Góźdż, Stanisław

2015-08-01

Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age- and sex-matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 + 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid. © 2015 UICC.

Impact of P2Y12 inhibition by clopidogrel on cardiovascular mortality in unselected patients treated by percutaneous coronary angioplasty: a prospective registry.

PubMed

El Ghannudi, Soraya; Ohlmann, Patrick; Meyer, Nicolas; Wiesel, Marie-Louise; Radulescu, Bogdan; Chauvin, Michel; Bareiss, Pierre; Gachet, Christian; Morel, Olivier

2010-06-01

The aim of this study was to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by Vasodilator-stimulated phosphoprotein flow cytometry test (VASP- FCT) predicts cardiovascular events in a high-risk population undergoing percutaneous coronary intervention (PCI). Impaired platelet responsiveness to clopidogrel is thought to be a determinant of cardiovascular events after PCI. The platelet VASP-FCT is a new assay specific to the P2Y(12) adenosine diphosphate receptor-pathway. In this test, platelet activation is expressed as platelet reactivity index (PRI). Four-hundred sixty-one unselected patients undergoing urgent (n = 346) or planned (n = 115) PCI were prospectively enrolled. Patients were classified as low-response (LR) and response (R) to clopidogrel, depending on their PRI. Optimal PRI cutoff was determined by receiver-operator characteristic curve analysis to 61% (LR: PRI > or =61% and R: PRI <61%). Follow-up was obtained at a mean of 9 +/- 2 months in 453 patients (98.3%). At follow-up, total cardiac mortality rates and possible and total stent thrombosis were higher in LR patients. Multivariate analysis identified creatinine clearance (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.93 to 0.98, p < 0.001), drug-eluting stent (HR: 5.73; 95% CI: 1.40 to 23.43, p = 0.015), C-reactive protein (HR: 1.01; 95% CI: 1.001 to 1.019, p = 0.024), and LR to clopidogrel (HR: 4.00; 95% CI: 1.08 to 14.80, p = 0.037) as independent predictors of cardiac death. The deleterious impact of LR to clopidogrel on cardiovascular death was significantly higher in patients implanted with drug-eluting stent. In patients undergoing PCI, LR to clopidogrel assessed by VASP-FCT is an independent predictor of cardiovascular death at the PRI cutoff value of > or =61%. The LR clinical impact seems to be dependent on the type of stent implanted. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Poststroke Aphasia Frequency, Recovery, and Outcomes: A Systematic Review and Meta-Analysis.

PubMed

Flowers, Heather L; Skoretz, Stacey A; Silver, Frank L; Rochon, Elizabeth; Fang, Jiming; Flamand-Roze, Constance; Martino, Rosemary

2016-12-01

To conduct a systematic review to elucidate the frequency, recovery, and associated outcomes for poststroke aphasia over the long-term. Using the Cochrane Stroke Strategy, we searched 10 databases, 13 journals, 3 conferences, and the gray literature. Our a priori protocol criteria included unselected samples of adult stroke patients from randomized controlled trials or consecutive cohorts. Two independent reviewers rated abstracts and articles for exclusion or inclusion, resolving discrepancies by consensus. We documented aphasia frequencies by stroke type and setting, and computed odds ratios (ORs) with their 95% confidence intervals (CIs) for outcomes. We retrieved 2168 citations, reviewed 248 articles, and accepted 50. Median frequencies for mixed stroke (ischemic and hemorrhagic) were 30% and 34% for acute and rehabilitation settings, respectively. Frequencies by stroke type were lowest for acute subarachnoid hemorrhage (9%) and highest for acute ischemic stroke (62%) when arrival to the hospital was ≤3 hours from stroke onset. Articles monitoring aphasia for 1 year demonstrated aphasia frequencies 2% to 12% lower than baseline. Negative outcomes associated with aphasia included greater odds of in-hospital death (OR=2.7; 95% CI, 2.4-3.1) and longer mean length of stay in days (mean=1.6; 95% CI, 1.0-2.3) in acute settings. Patients with aphasia had greater disability from 28 days (OR=1.5; 95% CI, 1.3-1.7) to 2 years (OR=1.7; 95% CI, 1.6-2.0) than those without aphasia. By 2 years, they used more rehabilitation services (OR=1.5; 95% CI, 1.3-1.6) and returned home less frequently (OR=1.4; 95% CI, 1.2-1.7). Reported frequencies of poststroke aphasia range widely, depending on stroke type and setting. Because aphasia is associated with mortality, disability, and use of health services, we recommend long-term interdisciplinary vigilance in the management of aphasia. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The feasibility and safety of applying the Magnetic Navigation System to manage chronically occluded vessels: a single centre experience.

PubMed

Ramcharitar, Steve; van der Giessen, Willem J; van der Ent, Martin; de Feyter, Pim; Serruys, Patrick W; van Geuns, Robert-Jan

2011-01-01

Applying the Magnetic Navigation System (MNS) to manage chronic total occlusions (CTOs). The MNS precisely directs a magnetised guidewire in vivo through two permanent external magnets. The first 43 consecutive MNS treated CTOs were retrospectively evaluated. Computed tomography coronary angiography (CTCA) co-integration with the MNS provided a virtual road map through the occlusion. Unsuccessful MNS cases were managed with bailout conventional guidewire techniques. Experienced CTO and MNS operators had unrestricted access to CTO devices and equipments. The MNS crossing success increased from 40% to 56% over 52 months and averaged 44.2% (19/43 patients). In 58.3% (14/24) of failed MNS cases the conventional wire approach was successful, giving an overall procedural success rate of 76.6%. Of those conventionally treated, two patients required pericardiocentesis. On average, 1.8 ± 0.9 stents (lengths 44.7 ± 21.4 mm and diameter 2.8 ± 0.4 mm) were implanted. Procedural times were lengthy (125.0 ± 35.3 min) requiring high fluoroscopy dosage (11980.2 ± 6457.9 Gy/cm2) and contrast media usage (388.8 ± 170.2 ml). Operators persevered less with magnetic wires (20.9 ± 12.4 min vs. 27.7 ± 24.4 min), and preferentially used the least stiff wire as first choice (53.5%). CTCA co-integration did not influence procedural outcome. As with conventional wires, higher magnetic wire successes occurred in low calcified lesions, those with a central stump and without bridging collaterals. In unselected CTOs, the magnetic wires are safe and feasible. Current modest success rates with a high procedural bailout rate implicate the need for improved magnetic guidewire technology comparable to available sophisticated conventional CTO wires. Randomised studies are needed to clarify the value of magnetic guided recanalisation.

Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

PubMed

Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

2017-07-01

Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding. Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The outcome of antenatal ultrasound diagnosed anomalies of the kidney and urinary tract in a large Danish birth cohort.

PubMed

Andrés-Jensen, Liv; Jørgensen, Finn Stener; Thorup, Jorgen; Flachs, Julie; Madsen, Jan Lysgaard; Maroun, Lisa Leth; Nørgaard, Pernille; Vinicoff, Pablo Gustavo; Olsen, Beth Härstedt; Cortes, Dina

2016-09-01

Antenatal ultrasound diagnosed anomalies of the kidney and urinary tract (AUDAKUT) are reported in 0.3%-5% on prenatal ultrasound (US) and 0.3%-4.5% on postnatal US. The anterior-posterior diameter of the renal pelvis (APD) is an essential measurement. Series with low threshold values of APD prenatally and postnatally will include healthy infants. It is important to avoid follow-up of such infants. In 2006, new Danish guidelines for AUDAKUT were introduced. Investigations of incidences and type of AUDAKUT based on Danish guidelines, including long-term follow-up. Cohort study. Copenhagen University Hospital Hvidovre and Copenhagen University Hospital Rigshospitalet, Denmark. Consecutive cases with AUDAKUT in the second and third trimesters, which were either terminated before 22 completed weeks of gestation or born in the 8-year period January 2006-December 2013. Patients were followed until June 2014. 50 193 live born children and 24 terminated fetuses (0.05%) were included. The prevalence of AUDAKUT was only 0.39% prenatally, 0.29% at first postnatal US and 0.22% at the end of follow-up, including terminated cases. The greater the prenatal and postnatal APD, the higher risk of febrile urinary tract infection (fUTI) and surgical intervention, and lower probability of resolution. 25% of the identified patients had fUTI and/or surgery. We recommend threshold values of APD at least 10 mm in the third trimester and in general at least 12 mm at first postnatal US for intensive follow-up. In this largest to date unselected birth cohort of AUDAKUT, the incidences of clinically significant AUDAKUT were in the lowest range of those previously published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Characteristics of compensated hypogonadism in patients with sexual dysfunction.

PubMed

Corona, Giovanni; Maseroli, Elisa; Rastrelli, Giulia; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2014-07-01

In the last few years, a view that subclinical endocrine disorders represent milder forms of the clinically overt disease has emerged. Accordingly, it has been proposed that compensated hypogonadism represents a genuine clinical subset of late-onset hypogonadism. The aim of the present study is to investigate the associations of compensated hypogonadism with particular clinical and psychological characteristics of male subjects complaining of sexual dysfunction. After excluding documented genetic causes of hypogonadism, an unselected consecutive series of 4,173 patients consulting our unit for sexual dysfunction was studied. Compensated hypogonadism was identified according to the European Male Ageing study criteria: total testosterone ≥10.5 nmol/L and luteinizing hormone >9.4 U/L. Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with results of the Structured Interview on Erectile Dysfunction (SIEDY) and ANDROTEST. One hundred seventy (4.1%) subjects had compensated hypogonadism, whereas 827 (19.8%) had overt hypogonadism. After adjustment for confounding factors, no specific sexual symptoms were associated with compensated hypogonadism. However, compensated hypogonadism individuals more often reported psychiatric symptoms, as detected by Middlesex Hospital Questionnaire score, when compared with both eugonadal and overt hypogonadal subjects (adjusted odds ratios = 1.018 [1.005;1.031] and 1.014 [1.001;1.028], respectively; both P < 0.005). In addition, subjects with compensated or overt hypogonadism had an increased predicted risk of cardiovascular events (as assessed by Progetto Cuore risk algorithm) when compared with eugonadal individuals. Accordingly, mortality related to major adverse cardiovascular events (MACEs), but not MACE incidence, was significantly higher in subjects with both compensated and overt hypogonadism when compared with eugonadal subjects. The present data do not support the concept that compensated (subclinical) hypogonadism represents a new clinical entity. The possibility that subclinical hypogonadism could be a normal response of the hypothalamus-pituitary-testis axis to somatic illness should be considered. Further studies are urgently needed to clarify this latter point. © 2014 International Society for Sexual Medicine.

Derivation and external validation of a case mix model for the standardized reporting of 30-day stroke mortality rates.

PubMed

Bray, Benjamin D; Campbell, James; Cloud, Geoffrey C; Hoffman, Alex; James, Martin; Tyrrell, Pippa J; Wolfe, Charles D A; Rudd, Anthony G

2014-11-01

Case mix adjustment is required to allow valid comparison of outcomes across care providers. However, there is a lack of externally validated models suitable for use in unselected stroke admissions. We therefore aimed to develop and externally validate prediction models to enable comparison of 30-day post-stroke mortality outcomes using routine clinical data. Models were derived (n=9000 patients) and internally validated (n=18 169 patients) using data from the Sentinel Stroke National Audit Program, the national register of acute stroke in England and Wales. External validation (n=1470 patients) was performed in the South London Stroke Register, a population-based longitudinal study. Models were fitted using general estimating equations. Discrimination and calibration were assessed using receiver operating characteristic curve analysis and correlation plots. Two final models were derived. Model A included age (<60, 60-69, 70-79, 80-89, and ≥90 years), National Institutes of Health Stroke Severity Score (NIHSS) on admission, presence of atrial fibrillation on admission, and stroke type (ischemic versus primary intracerebral hemorrhage). Model B was similar but included only the consciousness component of the NIHSS in place of the full NIHSS. Both models showed excellent discrimination and calibration in internal and external validation. The c-statistics in external validation were 0.87 (95% confidence interval, 0.84-0.89) and 0.86 (95% confidence interval, 0.83-0.89) for models A and B, respectively. We have derived and externally validated 2 models to predict mortality in unselected patients with acute stroke using commonly collected clinical variables. In settings where the ability to record the full NIHSS on admission is limited, the level of consciousness component of the NIHSS provides a good approximation of the full NIHSS for mortality prediction. © 2014 American Heart Association, Inc.

Glaucoma incidence in an unselected cohort of diabetic patients: is diabetes mellitus a risk factor for glaucoma? DARTS/MEMO collaboration. Diabetes Audit and Research in Tayside Study. Medicines Monitoring Unit.

PubMed

Ellis, J D; Evans, J M; Ruta, D A; Baines, P S; Leese, G; MacDonald, T M; Morris, A D

2000-11-01

To evaluate whether diabetes mellitus is a risk factor for the development of primary open angle glaucoma or ocular hypertension (OHT). A historical cohort study of an unselected population comprising all residents of the Tayside region of Scotland was performed using record linkage techniques followed by case note review. Ascertainment of prevalent diabetes was achieved using the Diabetes Audit and Research in Tayside Study (DARTS) validated regional diabetes register. Glaucoma and treated OHT were defined by encashment of community prescriptions and the statutory surgical procedure coding database. The study population comprised 6631 diabetic subjects and 166 144 non-diabetic subjects aged >40 years without glaucoma or OHT at study entry. 65 patients with diabetes and 958 without diabetes were identified as new cases of glaucoma or treated OHT during the 24 month study period, yielding a standardised morbidity ratio of 127 (95% CI, 96-158). Case note review demonstrated non-differential misclassification of prevalent glaucoma and OHT as incident disease (diabetic cohort 20%, non-diabetic cohort 24%; p=0.56) primarily as a result of non-compliance in medically treated disease. Removing misclassified cases and adjusting for age yielded an incidence of primary open angle glaucoma in diabetes of 1.1/1000 patient years (95% CI, 0.89-1. 31) compared to 0.7/1000 patient years (95% CI, 0.54-0.86) in the non-diabetic cohort; RR 1.57 (95% CI, 0.99-2.48). This study failed to confirm an association between diabetes mellitus and primary open angle glaucoma and ocular hypertension. A non-significant increase in diagnosed and treated disease in the diabetic population was observed, but evidence was also found that detection bias contributes to this association.

Health care utilization history, GOLD guidelines, and respiratory medication prescriptions in patients with COPD.

PubMed

Seaman, Joseph; Leonard, Anthony C; Panos, Ralph J

2010-04-07

The relationship between prior health care utilization and respiratory medication prescriptions in an unselected population of patients with COPD is not known. We determined the prescribed respiratory medications and respiratory and nonrespiratory health care encounters in 523 Veterans with COPD at the Cincinnati Veterans Affairs Medical Center between 2000 and 2005. Prescribed treatments were compared with the GOLD guidelines and each patient was classified as receiving less medications than recommended in the guidelines (G). Respiratory medications were G for 14% of the patients studied. For GOLD stages 1 and 2, G patients the most prior respiratory encounters during a 12 month period (0.31 +/- 0.073 (0.21, 0.47), 0.75 +/- 0.5 (0.37, 1.5), 1.1 +/- 0.27 (0.74, 1.6) visits/person/year, G, respectively, mean + standard error of mean (SEM) (95% confidence limits) 2 degrees of freedom (df) ANOVA P < 0.001 for prescription effect). For GOLD stages 3 and 4, G respectively, 2 df ANOVA P = 0.096) or for GOLD stages 3 and 4 (3.6 +/- 0.25 (3.2, 4.1) and 4.0 +/- 0.44 (3.3, 4.9) visits/person/year,

Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA.

PubMed

Smith, Wade S; Lev, Michael H; English, Joey D; Camargo, Erica C; Chou, Maggie; Johnston, S Claiborne; Gonzalez, Gilberto; Schaefer, Pamela W; Dillon, William P; Koroshetz, Walter J; Furie, Karen L

2009-12-01

Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries-likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify. The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression. Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score

Positive view and increased likely uptake of follow-up testing with analysis of cell-free fetal DNA as alternative to invasive testing among Danish pregnant women.

PubMed

Miltoft, Caroline B; Rode, Line; Tabor, Ann

2018-05-01

The aim of this study was to investigate the attitude (view, likely uptake and preferred strategy) towards cell-free fetal DNA (cfDNA) testing among pregnant women before a first-trimester risk assessment for trisomy 21 (unselected women) and after obtaining a high risk. Unselected and high-risk women attending first-trimester screening (Rigshospitalet, Copenhagen University Hospital) were invited to fill out the questionnaire Antenatal testing for Down syndrome as an online survey. The survey included 203 unselected and 50 high-risk women (response rates of 74.8% and 84.7%, respectively). Nearly all considered cfDNA testing a positive development in antenatal care, and 97.2% would like it to be offered. Offering cfDNA testing as an alternative to invasive testing would increase the uptake of follow-up testing compared with invasive testing alone (98.8% vs. 90.7%, p < 0.001). Women who would only accept follow up by cfDNA testing were more likely to continue an affected pregnancy (30.0% vs. 3.6%, p < 0.001) or have doubts about termination (50.0% vs. 32.1%, p < 0.001). Offering cfDNA testing would likely increase the uptake of follow-up testing without a corresponding rise in the termination rate of affected fetuses as some women test for information only. However, both unselected and high-risk women had overwhelmingly positive views underlining attention to avoid routinization. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

PubMed

Santhirapala, Vatshalan; Williams, Louisa C; Tighe, Hannah C; Jackson, James E; Shovlin, Claire L

2014-01-01

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity. 165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100. There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up. Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses.

Arterial Oxygen Content Is Precisely Maintained by Graded Erythrocytotic Responses in Settings of High/Normal Serum Iron Levels, and Predicts Exercise Capacity: An Observational Study of Hypoxaemic Patients with Pulmonary Arteriovenous Malformations

PubMed Central

Santhirapala, Vatshalan; Williams, Louisa C.; Tighe, Hannah C.; Jackson, James E.; Shovlin, Claire L.

2014-01-01

Background Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity. Methodology 165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100. Principal Findings There was wide variation in SaO2 on air (78.5–99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up. Significance Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses. PMID:24637882

Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a multinational study.

PubMed

James, P D; Mahlangu, J; Bidlingmaier, C; Mingot-Castellano, M E; Chitlur, M; Fogarty, P F; Cuker, A; Mancuso, M E; Holme, P A; Grabell, J; Satkunam, N; Hopman, W M; Mathew, P

2016-11-01

There has been increasing recognition in recent years that female carriers of haemophilia manifest abnormal bleeding; however, data on the use of bleeding assessment tools in this population are lacking. Our objective was to validate the ISTH-BAT in haemophilia carriers to describe bleeding symptoms and allow for comparisons with factor levels and other patient groups. This was a prospective, observational, cross-sectional study performed by members of Global Emerging HEmostasis Panel (GEHEP). Unselected consecutive haemophilia carriers were recruited and a CRF and the ISTH-BAT were completed by study personnel. A total of 168 haemophilia carriers were enrolled: 155 haemophilia A and 13 haemophilia B. The mean age was 40 years (range: 20-82). Carriers had higher mean bleeding scores (BS) compared with age-matched controls (n = 46; 5.7 vs. 1.43; P < 0.0001) and Type 3 VWD OC (n = 32; 3.0; P = 0.009), but lower BS compared with women with Type 1 VWD (n = 83; 8.7; P < 0.0001). Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/FIX levels. There was a significant but weak negative correlation between BS and factor level (Spearman's r 2  = -0.36, P < 0.001). Our results show that haemophilia carriers experience abnormal bleeding, including haemarthrosis. Overall, BS in women with Type 1 VWD > haemophilia carriers > Type 3 VWD OC > controls. Understanding the performance of the ISTH-BAT in this population is a critical step in future research aimed at investigating the underlying pathophysiology of abnormal bleeding, with the ultimate goal of optimizing treatment. © 2016 John Wiley & Sons Ltd.

Anaemia, iron deficiency and iron deficiency anaemia among blood donors in Port Harcourt, Nigeria.

PubMed

Jeremiah, Zaccheaus Awortu; Koate, Baribefe Banavule

2010-04-01

There is paucity of information on the effect of blood donation on iron stores in Port Harcourt, Nigeria. The present study was, therefore, designed to assess, using a combination of haemoglobin and iron status parameters, the development of anaemia and prevalence of iron deficiency anaemia in this area of Nigeria. Three hundred and forty-eight unselected consecutive whole blood donors, comprising 96 regular donors, 156 relatives of patients and 96 voluntary donors, constituted the study population. Three haematological parameters (haemoglobin, packed cell volume, and mean cell haemoglobin concentration) and four biochemical iron parameters (serum ferritin, serum iron, total iron binding capacity and transferrin saturation) were assessed using standard colorimetric and ELISA techniques. The prevalence of anaemia alone (haemoglobin <11.0 g/dL) was 13.7%. The prevalence of isolated iron deficiency (serum ferritin <12 ng/mL) was 20.6% while that of iron-deficiency anaemia (haemoglobin <11.0 g/dL + serum ferritin <12.0 ng/mL) was 12.0%. Among the three categories of the donors, the regular donors were found to be most adversely affected as shown by the reduction in mean values of both haematological and biochemical iron parameters. Interestingly, anaemia, iron deficiency and iron-deficiency anaemia were present almost exclusively among regular blood donors, all of whom were over 35 years old. Anaemia, iron deficiency and iron-deficiency anaemia are highly prevalent among blood donors in Port Harcourt, Nigeria. It will be necessary to review the screening tests for the selection of blood donors and also include serum ferritin measurement for the routine assessment of blood donors, especially among regular blood donors.

Trace element analysis by PIXE in several biomedical fields

NASA Astrophysics Data System (ADS)

Weber, G.; Robaye, G.; Bartsch, P.; Collignon, A.; Beguin, Y.; Roelandts, I.; Delbrouck, J. M.

1984-04-01

Since 1980 in the University of Liége trace element analysis by PIXE has been developed in several directions, among these: the elemental composition of lung parenchyma, hilar lymph nodes, blood content in hematological disorders and renal insufficiency. The content in trace elements of lung tumor and surrounding tissue is measured and compared to similar content previously obtained on unselected patients of comparable ages. The normalization of the bromine deficiency observed in hemodialized patients is achieved by using a dialyzing bath doped with NaBr in order to obtain a normal bromine level of 5.7 μg/ml. The content of Cu, Zn, Br and Se in blood serum from more than 100 patients suffering from malignant hemopathy has been measured. The results are compared with a reference group. These oligoelements have also been measured sequentially for patients under intensive chemotherapy in acute myeloid leukemia.

Cognitive mediation of clinical improvement after intensive exposure therapy of agoraphobia and social phobia.

PubMed

Vögele, Claus; Ehlers, Anke; Meyer, Andrea H; Frank, Monika; Hahlweg, Kurt; Margraf, Jürgen

2010-03-01

The present study investigated cognitive mediation of clinical improvement in patients with agoraphobia (N=427) or social phobia (N=98) receiving high-density exposure therapy in a naturalistic clinical treatment setting. Patients were assessed before therapy, 6 weeks after the end of therapy, and 1 year thereafter, using a self-report assessment battery. Lower level mediation analyses provided support for the notion that cognitive changes partially mediate clinical improvement after exposure therapy. Changes in cognitions relating to physical catastrophes mediated treatment outcome only for patients with agoraphobia, whereas changes in cognitions about loss of control mediated outcome for both agoraphobia and social phobia patients. Changes in relationship satisfaction did not mediate symptomatic improvement. The results extend previous findings by demonstrating mediation in an unselected clinical sample and by providing evidence for the specificity of mediation effects. They further support the importance of cognitive changes in cognitive-behavior therapy. (c) 2009 Wiley-Liss, Inc.

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

PubMed

Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

2012-04-01

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density.

PubMed

Weber, Thomas J; Koh, James; Thomas, Samantha M; Hogue, Joyce A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

2017-09-01

A subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown. We sought to identify new mechanistic indices that could inform more personalized management of PHPT. Pre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables. An unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled. Calcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior. Parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50<3.0 and ≥3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43-2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: -3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p<0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of -0.35 (p=0.02). Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular evidence of simian virus 40 infections in children

NASA Technical Reports Server (NTRS)

Butel, J. S.; Arrington, A. S.; Wong, C.; Lednicky, J. A.; Finegold, M. J.

1999-01-01

Recent studies have detected simian virus 40 (SV40) DNA in certain human tumors and normal tissues. The significance of human infections by SV40, which was first discovered as a contaminant of poliovirus vaccines used between 1955 and 1963, remains unknown. The occurrence of SV40 infections in unselected hospitalized children was evaluated. Polymerase chain reaction and DNA sequence analyses were done on archival tissue specimens from patients positive for SV40 neutralizing antibody. SV40 DNA was identified in samples from 4 of 20 children (1 Wilms' tumor, 3 transplanted kidney samples). Sequence variation among SV40 regulatory regions ruled out laboratory contamination of specimens. This study shows the presence of SV40 infections in pediatric patients born after 1982.

Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia

PubMed Central

Serrano-Fernandez, Pablo; Dymerska, Dagmara; Kurzawski, Grzegorz; Derkacz, Róża; Sobieszczańska, Tatiana; Banaszkiewicz, Zbigniew; Roomere, Hanno; Oitmaa, Eneli; Metspalu, Andres; Janavičius, Ramūnas; Elsakov, Pavel; Razumas, Mindaugas; Petrulis, Kestutis; Irmejs, Arvīds; Miklaševičs, Edvīns; Scott, Rodney J.; Lubiński, Jan

2015-01-01

The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC) raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668), already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition. Material and Methods. DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls), Latvia (81 cases and controls), Lithuania (123 cases and controls), and Poland (795 cases and controls). Results. Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (corrected P value = 0.018 for the Estonian, corrected P value = 0.0034 for the Lithuanian, and corrected P value = 0.0076 for the Polish sample). Conclusions. The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers. PMID:26101521

Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia.

PubMed

Serrano-Fernandez, Pablo; Dymerska, Dagmara; Kurzawski, Grzegorz; Derkacz, Róża; Sobieszczańska, Tatiana; Banaszkiewicz, Zbigniew; Roomere, Hanno; Oitmaa, Eneli; Metspalu, Andres; Janavičius, Ramūnas; Elsakov, Pavel; Razumas, Mindaugas; Petrulis, Kestutis; Irmejs, Arvīds; Miklaševičs, Edvīns; Scott, Rodney J; Lubiński, Jan

2015-01-01

The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC) raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668), already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition. Material and Methods. DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls), Latvia (81 cases and controls), Lithuania (123 cases and controls), and Poland (795 cases and controls). Results. Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (corrected P value = 0.018 for the Estonian, corrected P value = 0.0034 for the Lithuanian, and corrected P value = 0.0076 for the Polish sample). Conclusions. The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers.

Evaluation of nasogastric tubes to enable differentiation between upper and lower gastrointestinal bleeding in unselected patients with melena.

PubMed

Kessel, Boris; Olsha, Oded; Younis, Aurwa; Daskal, Yaakov; Granovsky, Emil; Alfici, Ricardo

2016-02-01

Gastrointestinal (GI) bleeding is a common surgical problem. The aim of this study was to evaluate how insertion of the nasogastric tube may enable differentiation between upper and lower GI bleeding in patients with melena. A retrospective study involving patients admitted to our surgery division with a melena was carried out between the years 2010 and 2012. A total of 386 patients were included in the study. Of these, 279 (72.2%) patients had negative nasogastric aspirate. The sensitivity of examination of nasogastric aspirate to establish the upper GI as the source of bleeding was only 28% and the negative predictive value of a negative nasogastric aspirate was less than 1%. Most patients who initially presented with melena and were found to have upper GI bleeding had a negative nasogastric aspirate. Insertion of a nasogastric tube does not affect the clinical decision to perform upper endoscopy and should not be routinely carried out.

Direct immunofluorescence of normal skin in rheumatoid arthritis.

PubMed

Fitzgerald, O M; Barnes, L; Woods, R; McHugh, L; Barry, C; O'Loughlin, S

1985-11-01

The clinical significance of previously described immunoglobulin and complement deposition in the superficial dermal vessel walls of patients with rheumatoid arthritis is unknown. In the present study, skin biopsies were obtained from the normal forearm and buttock of 48 unselected patients with rheumatoid arthritis and were examined by direct immunofluorescence (IF) for the presence of immunoglobulin (IgG,A,M) and complement (C3) in the vessel walls. Deposits of C3, IgM or IgG were detected in 10 patients. Five patients had deposits at the forearm sample alone, four patients had deposits at both biopsy sites, while one patient was positive at the buttock alone. Clinical features were similar in patients with and without vessel IF. However, patients with IF were significantly more seropositive with lower levels of complement and raised levels of serum IgA and IgM. There was also an increased level of circulating IgG immune complexes in these patients. Further analysis following exclusion of seronegative patients revealed similar results. This study suggests that the presence of vessel IF identifies a subgroup of patients who have evidence of more severe immunological disturbance.

Changes in plasma levels of B-type natriuretic peptide with acute exacerbations of chronic obstructive pulmonary disease.

PubMed

Nishimura, Koichi; Nishimura, Takashi; Onishi, Katsuya; Oga, Toru; Hasegawa, Yoshinori; Jones, Paul W

2014-01-01

Elevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). To examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD). In all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited. Plasma BNP levels were compared cross-sectionally and longitudinally. Transthoracic echocardiographic examinations were also performed in the hospitalized subjects. In the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9-129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0-45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0-53.7) for grade II; 22.1 (9.1-52.6) for grade III; and 17.2 (9.6-22.9) pg/mL for grade I V, all P<0.001. In 15 subjects studied prospectively, the median plasma BNP level was 19.4 (9.8-32.2) pg/mL before AECOPD, 72.7 (27.7-146.3) pg/mL during AECOPD, and 14.6 (12.9-39.0) pg/mL after AECOPD (P<0.0033 and P<0.0013, respectively). Median plasma BNP levels during AECOPD were significantly higher in ten unsuccessfully discharged subjects 260.5 (59.4-555.0) than in 48 successfully discharged subjects 48.5 (24.2-104.0) pg/mL (P=0.0066). Only 5.6% of AECOPD subjects were associated with systolic dysfunction defined as a left ventricular ejection fraction (LVEF) <50%; a further 7.4% were considered to have impaired relaxation defined as an E/A wave velocity ratio <0.8 and a deceleration time of E >240 ms. BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman's rank correlation coefficient =0.353, P=0.018), but they were not correlated with the LVEF (Spearman's rank correlation coefficient =-0.221, P=0.108). A modest elevation of plasma BNP is observed during AECOPD. It appears that AECOPD may have an impact on plasma BNP levels that is not attributable to heart failure.

Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: The Spanish REASON study.

PubMed

Esteban, E; Majem, M; Martinez Aguillo, M; Martinez Banaclocha, N; Dómine, M; Gómez Aldaravi, L; Juan, O; Cajal, R; Gonzalez Arenas, M C; Provencio, M

2015-06-01

The aim of the REASON study is to determine the frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC) patients in Spain (all histologies), and to better understand the clinical factors (gender, smoking habits and histological subtypes) that may be associated with EGFR mutations, in an unselected sample of aNSCLC patients. All newly diagnosed aNSCLC patients from 40 selected centers in Spain were prospectively included for a 6-month period. Patient characteristics were obtained from clinical records. Mutation testing was performed on available tumor samples. Exploratory analyses were performed to characterize the clinico-pathological factors associated with presence of EGFR mutations. From March 2010 to March 2011, 1113 patients were included in the study, of which 1009 patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis was not feasible in 146/1113 patients (13.1%) due to either sample unavailability (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113 patients (2.3%) were excluded due to unavailable information. Most patients (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%) or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar, 11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6% (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21 (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found in 22/505 samples (4.4%). The estimated prevalence of sensitizing EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly diagnosed aNSCLC patients in Spain (all histologies) is consistent with previous published data in Caucasian patients. When a sample is available, EGFR mutation testing is feasible in over 90% of cases, and may therefore be suitable for routine clinical practice. CLINICALTRIALS. NCT01081496. Copyright © 2015 Elsevier Ltd. All rights reserved.

Behavioral effects of bidirectional selection for behavior towards human in virgin and lactate Norway rats.

PubMed

Konoshenko, Maria Yu; Plyusnina, Irina Z

2012-06-01

Although numerous studies have demonstrated strong differences in behavioral, hormonal and neurobiological characteristics between male rats selected for elimination (tame) and enhancement (aggressive) of aggressiveness towards humans, few studies have examined changes in female behavior under this selection. The objective of the current work was to evaluate the effects of bidirectional selection for aggressiveness towards humans on behavioral profiles of virgin and lactating rats compared with the behavior in tame, aggressive and unselected (wild-type) females. The behavior of virgin females was studied using the light-dark box, the startle response test and the modified glove test. Tame females were less anxious and more tolerant towards humans than unselected and aggressive rats. Principal component analysis of all behavioral parameters produced three independent factors, explaining 66.37% of the total variability. The measures of behavior towards humans and the measures of anxiety mainly loaded on PC1 (first principal component) which separated the tame females from the unselected and aggressive ones. These data suggest the genetic correlation between the selected behavior towards humans and anxiety-related behavior in virgin rats. No significant effect of line was found for PC2 scores, associated with risk assessment behavior. Measurements of freezing behavior mainly loaded on PC3, and this component separated rats of different genetic groups from each other. The behavior of lactating rats was studied in maternal defense and pup retrieval tests. Females of selected lines did not significantly differ in behavioral measurements of these tests and were characterized by higher maternal motivation than unselected rats. It is suggested that long-term breeding of tame and aggressive rats in captivity has reduced the threshold for maternal behavior. Copyright © 2012 Elsevier B.V. All rights reserved.

Is the pencil point spinal needle a better choice in younger patients? A comparison of 24G Sprotte with 27G Quincke needles in an unselected group of general surgical patients below 46 years of age.

PubMed

Brattebø, G; Wisborg, T; Rodt, S A; Røste, I

1995-05-01

Reports have indicated that there are less postoperative complaints after the use of pencil pointed spinal needles. We compared a 24G Sprotte needle with a 27G Quincke needle in a randomised study of 200 healthy patients (49% females), aged 15-46 years. Four patients (2%) reported postdural puncture headache, three with the 24G Sprotte needle and one with the 27G Quincke needle. Thirteen patients (7%) suffered with nonspecific headache, with no significant difference between the two groups. Of the 57 (29%) who reported backpain, a significantly higher proportion had received spinal anaesthesia with the Sprotte needle (OR = 2.06). There was a significantly higher incidence of insufficient blocks after dural puncture with the Sprotte needle. Ease of needle insertion and number of puncture attempts was the same for both needle types.

VCAM-1 serum levels are associated with arthropathy in hereditary haemochromatosis.

PubMed

Nell-Duxneuner, Valerie; Axmann, Roland; Husar-Memmer, Emma; Dallos, Tomás; Datz, Christian; Stadlmayr, Andreas; Aigner, Elmar; Englbrecht, Matthias; Schett, Georg; Zwerina, Jochen

2013-12-01

The aim of this study was to assess the role of vascular adhesion molecule 1 (VCAM-1) in patients with hereditary haemochromatosis (HH) with or without arthropathy. Sera from a large cross-sectional cohort of unselected HH patients (n=147) were obtained and compared to an age-matched and sex-matched control group. Serum levels of VCAM-1 were measured by ELISA and were correlated with clinical measures. VCAM-1 serum levels were elevated in HH patients as compared to matched controls (mean 913±456 vs 654±451 ng/ml, p<0.0001). Within the HH patient group, VCAM-1 levels were much higher in patients with arthropathy and joint replacement surgery. VCAM-1 levels correlated well with radiographic measures of HH arthropathy (r=0.36, p<0.0001). Multivariate regression analysis confirmed a highly significant association of VCAM-1 serum levels and the presence of HH arthropathy, independent from diabetes, body mass index and age. VCAM-1 serum levels emerge as a biomarker for haemochromatosis arthropathy.

Enhanced broadband absorption in nanowire arrays with integrated Bragg reflectors

NASA Astrophysics Data System (ADS)

Aghaeipour, Mahtab; Pettersson, Håkan

2018-05-01

A near-unity unselective absorption spectrum is desirable for high-performance photovoltaics. Nanowire (NW) arrays are promising candidates for efficient solar cells due to nanophotonic absorption resonances in the solar spectrum. The absorption spectra, however, display undesired dips between the resonance peaks. To achieve improved unselective broadband absorption, we propose to enclose distributed Bragg reflectors (DBRs) in the bottom and top parts of indium phosphide (InP) NWs, respectively. We theoretically show that by enclosing only two periods of In0.56Ga0.44As/InP DBRs, an unselective 78% absorption efficiency (72% for NWs without DBRs) is obtained at normal incidence in the spectral range from 300 nm to 920 nm. Under oblique light incidence, the absorption efficiency is enhanced up to about 85% at an incidence angle of 50°. By increasing the number of DBR periods from two to five, the absorption efficiency is further enhanced up to 95% at normal incidence. In this work, we calculated optical spectra for InP NWs, but the results are expected to be valid for other direct band gap III-V semiconductor materials. We believe that our proposed idea of integrating DBRs in NWs offers great potential for high-performance photovoltaic applications.

The derivation and validation of a simple model for predicting in-hospital mortality of acutely admitted patients to internal medicine wards.

PubMed

Sakhnini, Ali; Saliba, Walid; Schwartz, Naama; Bisharat, Naiel

2017-06-01

Limited information is available about clinical predictors of in-hospital mortality in acute unselected medical admissions. Such information could assist medical decision-making.To develop a clinical model for predicting in-hospital mortality in unselected acute medical admissions and to test the impact of secondary conditions on hospital mortality.This is an analysis of the medical records of patients admitted to internal medicine wards at one university-affiliated hospital. Data obtained from the years 2013 to 2014 were used as a derivation dataset for creating a prediction model, while data from 2015 was used as a validation dataset to test the performance of the model. For each admission, a set of clinical and epidemiological variables was obtained. The main diagnosis at hospitalization was recorded, and all additional or secondary conditions that coexisted at hospital admission or that developed during hospital stay were considered secondary conditions.The derivation and validation datasets included 7268 and 7843 patients, respectively. The in-hospital mortality rate averaged 7.2%. The following variables entered the final model; age, body mass index, mean arterial pressure on admission, prior admission within 3 months, background morbidity of heart failure and active malignancy, and chronic use of statins and antiplatelet agents. The c-statistic (ROC-AUC) of the prediction model was 80.5% without adjustment for main or secondary conditions, 84.5%, with adjustment for the main diagnosis, and 89.5% with adjustment for the main diagnosis and secondary conditions. The accuracy of the predictive model reached 81% on the validation dataset.A prediction model based on clinical data with adjustment for secondary conditions exhibited a high degree of prediction accuracy. We provide a proof of concept that there is an added value for incorporating secondary conditions while predicting probabilities of in-hospital mortality. Further improvement of the model performance and validation in other cohorts are needed to aid hospitalists in predicting health outcomes.

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

PubMed

Davenport, Andrew

2009-01-01

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

Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors.

PubMed

Philbin, E F; Rocco, T A; Lindenmuth, N W; Ulrich, K; Jenkins, P L

2000-12-01

Among patients with heart failure, there is controversy about whether there are clinical features and laboratory tests that can differentiate patients who have low ejection fractions from those with normal ejection fractions. The usefulness of angiotensin-converting enzyme (ACE) inhibitors among heart failure patients who have normal left ventricular ejection fractions is also not known. From a registry of 2,906 unselected consecutive patients with heart failure who were admitted to 10 acute-care community hospitals during 1995 and 1997, we identified 1291 who had a quantitative measurement of their left ventricular ejection fraction. Patients were separated into three groups based on ejection fraction: < or =0.39 (n = 741, 57%), 0.40 to 0.49 (n = 238, 18%), and > or =0.50 (n = 312, 24%). In-hospital mortality, prescription of ACE inhibitors at discharge, subsequent rehospitalization, quality of life, and survival were measured; survivors were observed for at least 6 months after hospitalization. The mean (+/- SD) age of the sample was 75+/-11 years; the majority (55%) of patients were women. In multivariate models, age >75 years, female sex, weight >72.7 kg, and a valvular etiology for heart failure were associated with an increased probability of having an ejection fraction > or =0.50; a prior history of heart failure, an ischemic or idiopathic cause of heart failure, and radiographic cardiomegaly were associated with a lower probability of having an ejection fraction > or =0.50. Total mortality was lower in patients with an ejection fraction > or =0.50 than in those with an ejection fraction < or =0.39 (odds ratio [OR] = 0.69, 95% confidence interval [CI 0.49 to 0.98, P = 0.04). Among hospital survivors with an ejection fraction of 0.40 to 0.49, the 65% who were prescribed ACE inhibitors at discharge had better mean adjusted quality-of-life scores (7.0 versus 6.2, P = 0.02), and lower adjusted mortality (OR = 0.34, 95% CI: 0.17 to 0.70, P = 0.01) during follow-up than those who were not prescribed ACE inhibitors. Among hospital survivors with an ejection fraction > or =0.50, the 45% who were prescribed ACE inhibitors at discharge had better (lower) adjusted New York Heart Association (NYHA) functional class (2.1 versus 2.4, P = 0.04) although there was no significant improvement in survival. Among patients treated for heart failure in community hospitals, 42% of those whose ejection fraction was measured had a relatively normal systolic function (ejection fraction > or 0.40). The clinical characteristics and mortality of these patients differed from those in patients with low ejection fractions. Among the patients with ejection fractions > or =0.40, the prescription of ACE inhibitors at discharge was associated favorable effects.

Surgical restoration of vas continuity after vasectomy: further clinical evaluation of a new operation technique.

PubMed

Pardanani, D S; Kothari, M L; Pradhan, S A; Mahendrakar, M N

1974-04-01

20 unselected former vasectomy patients were subjected to scrotal exploration and vas recanalization operation. Anastomosis was carried out using a large diameter silicone rubber splint; the splint was removed 7 days postoperatively. No complications or side effects were encountered, and there were no patient complaints of discomfort or pain. 92.3% of the men considered satisfactory candidates for recanalization had successful results, and 30.8% of their wives became pregnant. The low fertility rate following successful vas recanalization is not understood. The 2 conditions which were found to be unfavorable for vas recanalization were a vasectomy where a long segment of the vas had been excised or where the vas section had been made very low and involved its convoluted segment.

Understanding the Key to Targeting the IGF Axis in Cancer: A Biomarker Assessment

PubMed Central

Lodhia, Kunal Amratlal; Tienchaiananda, Piyawan; Haluska, Paul

2015-01-01

Type 1 insulin like growth factor receptor (IGF-1R) targeted therapies showed compelling pre-clinical evidence; however, to date, this has failed to translate into patient benefit in Phase 2/3 trials in unselected patients. This was further complicated by the toxicity, including hyperglycemia, which largely results from the overlap between IGF and insulin signaling systems and associated feedback mechanisms. This has halted the clinical development of inhibitors targeting IGF signaling, which has limited the availability of biopsy samples for correlative studies to understand biomarkers of response. Indeed, a major factor contributing to lack of clinical benefit of IGF targeting agents has been difficulty in identifying patients with tumors driven by IGF signaling due to the lack of predictive biomarkers. In this review, we will describe the IGF system, rationale for targeting IGF signaling, the potential liabilities of targeting strategies, and potential biomarkers that may improve success. PMID:26217584

Prevalence of pathogenic yeasts and humoral antibodies to candida in diabetic patients.

PubMed Central

Odds, F C; Evans, E G; Taylor, M A; Wales, J K

1978-01-01

The prevalence of oral yeasts and humoral precipitating antibodies to candida was estimated in 204 unselected diabetic patients (172 outpatients and 32 inpatients). Yeasts, mainly Candida albicans, were isolated from the mouths of 41% of the outpatients and precipitins were found in 17.5% although none of the patients had clinically overt candidiasis. The extent of oral yeast colonisation and incidence of antibodies was not related to their antidiabetic treatment or to the duration of their diabetes. It was, however, related to the blood glucose and urine sugar levels at the time they were sampled, the highest incidence being among the diabetic inpatients with high blood glucose levels at the time of sampling and the lowest among outpatients with normal blood glucose levels at the time of sampling. There was no such correlation when diabetic control over the previous 12-month period was considered. PMID:711913

[Family study of patients with aspirin intolerance and rhinosinusitis].

PubMed

May, A; Wagner, D; Langenbeck, U; Weber, A

2000-09-01

The high prevalence of aspirin intolerance in asthmatics and patients with nasal polyps as well as reports of familial clustering suggest a genetic disposition of this disease. Our study aimed at obtaining further evidence of hereditary factors in this disease. We included 33 unselected patients from 28 families with aspirin intolerance and rhinosinusitis in this study. Controls were recruited from individuals treated in our ENT clinic for diseases other than aspirin intolerance (n = 52). A questionnaire focused on family histories as well as reports on diseases of the upper respiratory tract or allergies. ASS intolerance was verified either by bronchial or nasal provocation tests. We found cases of aspirin intolerance among parents, siblings, and children of ASS intolerant probands. The children of probands had nasal polyps and rhinosinusitis more often than the children of controls. We propose that ASS intolerance with nasal polyps and asthma represents a complex phenotype, with genetic and environmental factors contributing to its manifestation.

Intravitreal aflibercept versus intravitreal ranibizumab in patients with age-related macular degeneration: a comparative effectiveness study.

PubMed

Smit, Cornelis; Wiertz-Arts, Karin; van de Garde, Ewoudt Mw

2018-06-01

A hospital-wide, unselected switch of ranibizumab to aflibercept in treatment of age-related macular degeneration (AMD) allowed us to compare the clinical effectiveness of these agents. In a single-center before-after, observational study design new AMD-patients started with aflibercept treatment in 2013-2014 were compared with a control group of AMD-patients on ranibizumab before the switch. The mean difference in visual acuity (in logMAR units) after 1 year was comparable (+0.012 [aflibercept, n = 37] vs +0.17 [ranibizumab, n = 30], p = 0.154). However, the aflibercept-group did receive more intravitreal injections (5.8 vs 4.7 injections, p = 0.004) and were treated longer (265.7 vs 197.7 days; p = 0.011). With no difference in clinical effectiveness, longer treatment intervals for aflibercept should be investigated.

Relative prevalence of Aboriginal patients in a Canadian uveitic population.

PubMed

Roy, Mili

2012-04-01

To determine whether the prevalence of Aboriginal patients in a consecutive series of patients with uveitis differs significantly from the prevalence of Aboriginal persons in the general population. Retrospective chart review. 133 consecutive patients with uveitis. The proportion of Aboriginal patients in a series of 133 consecutive patients with uveitis was compared to the proportion of Aboriginal persons within the general population to determine whether Aboriginal patients were under- or overrepresented in the population with uveitis, relative to their numbers in the population in general. The main outcome measure was the self-reported race of patients. The mean age, sex, and prior disease duration were also compared between Aboriginal and non-Aboriginal patients in the consecutive series. There was no significant difference (p = 0.84) between the proportion of Aboriginal persons in the uveitis population studied (22 of 133; 16.5%) compared to general population census data (15.5% Aboriginal). Mean age at presentation was 36.8 years in the Aboriginal population versus 47.3 years in the control non-Aboriginal group (p = 0.01). Mean prior disease duration was 20.3 months in the Aboriginal population versus 21.1 months in the control group (p = 0.79). The gender proportion was 68.2% female in the Aboriginal group versus 53.2% female in the non-Aboriginal group (p = 0.02). This study finds no statistically significant difference between the prevalence of Aboriginal versus non-Aboriginal persons occurring within a consecutive series of uveitis patients as compared to the general population. Mean age at presentation was significantly younger, and female preponderance was significantly greater in the Aboriginal than in the non-Aboriginal group. Prior disease duration was comparable in the 2 groups. Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

A Novel Assay for the Identification of NOTCH1 PEST Domain Mutations in Chronic Lymphocytic Leukemia

PubMed Central

Petroni, Roberta Cardoso; Muto, Nair Hideko; Sitnik, Roberta; de Carvalho, Flavia Pereira; Bacal, Nydia Strachman; Velloso, Elvira Deolinda Rodrigues Pereira; Oliveira, Gislaine Borba; Pinho, João Renato Rebello; Torres, Davi Coe; Mansur, Marcela Braga; Hassan, Rocio; Lorand-Metze, Irene Gyongyvér Heidemarie; Chiattone, Carlos Sérgio; Hamerschlak, Nelson; Mangueira, Cristovão Luis Pitangueira

2016-01-01

Aims. To develop a fast and robust DNA-based assay to detect insertions and deletions mutations in exon 34 that encodes the PEST domain of NOTCH1 in order to evaluate patients with chronic lymphocytic leukemia (CLL). Methods. We designed a multiplexed allele-specific polymerase chain reaction (PCR) combined with a fragment analysis assay to detect specifically the mutation c.7544_7545delCT and possibly other insertions and deletions in exon 34 of NOTCH1. Results. We evaluated our assay in peripheral blood samples from two cohorts of patients with CLL. The frequency of NOTCH1 mutations was 8.4% in the first cohort of 71 unselected CLL patients. We then evaluated a second cohort of 26 CLL patients with known cytogenetic abnormalities that were enriched for patients with trisomy 12. NOTCH1 mutations were detected in 43.7% of the patients with trisomy 12. Conclusions. We have developed a fast and robust assay combining allele-specific PCR and fragment analysis able to detect NOTCH1 PEST domain insertions and deletions. PMID:28074183

A recurrent CHEK2 p.H371Y mutation is associated with breast cancer risk in Chinese women.

PubMed

Liu, Yin; Liao, Ji; Xu, Ye; Chen, Weiqiu; Liu, Dongyun; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xu, Xingzhi; Xie, Yuntao

2011-09-01

The association between the CHEK2 and breast cancer risk in Chinese women is unknown. Here, we screened the full CHEK2 coding sequence in 118 Chinese familial breast cancer cases who are negative for mutations in BRCA1 and BRCA2, one recurrent mutation, CHEK2 c.1111C>T (p.H371Y), was identified in five index cases in this cohort. Functional analysis suggested that CHEK2 p.H371Y was a pathogenic mutation that resulted in decreased kinase activity. We further screened the CHEK2 p.H371Y mutation in 909 unselected breast cancer cases and 1,228 healthy individuals. The frequencies of the CHEK2 p.H371Y in familial and unselected breast cancer cases and controls were 4.24% (5/118), 1.76% (16/909), and 0.73% (9/1228), respectively. The p.H371Y mutation was significantly associated with increased breast cancer risk in unselected breast cancer (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.07-5.52, P = 0.034). Our results indicate that the recurrent mutation, p.H371Y, confers a moderate risk of breast cancer in Chinese women. © 2011 Wiley-Liss, Inc.

Bone breaking strength and apparent metabolisability of calcium and phosphorus in selected and unselected broiler chicken genotypes.

PubMed

McDevitt, R M; McEntee, G M; Rance, K A

2006-10-01

1. The present study examined the bone strength and apparent mineral metabolisability of a selected broiler chicken compared with those of a relatively unselected genotype. 2. Selected (SB) and unselected genotypes (UB) were reared under standard conditions and were fed on either a high quality (HQ) or a low quality (LQ) diet. Tibiotarsi samples were collected at 42 d from SB and compared to tibiotarsi from UB of the same age and the same body mass (BM). 3. Bones were assessed for: bone breaking strength (BBS), morphology (weight and length), and both organic (OM) and inorganic content (ASH). Apparent dry matter digestibility and the coefficient of apparent metabolisability of calcium and phosphorus were determined at the same BM. 4. The BBS of SB (214 +/- 9 N) was greater than that of same-age UB (119 +/- 8 N) but the same as that of same-BM UB (218 +/- 10 N). At the same age, the SB had stronger, heavier bones with more ash and organic matter per unit length of tibiotarsus than UB. At the same BM, the tibiotarsi of the SB were shorter and lighter, with a higher ash and a similar organic content than the bones of the UB. At the same BM, BBS was about 15% lower in both genotypes fed on the LQ compared to the HQ diet. 5. The coefficients of apparent metabolisability of calcium and phosphorus were the same in both genotypes when fed on the HQ diet, but were lower in the SB than in the UB genotype when the birds were given the LQ diet. 6. The tibiotarsi of the selected broilers were stronger, or at least as strong, as those of the unselected broiler genotype, which may be due to similar levels of apparent calcium metabolisability of the selected chickens.

Manipulation Detection and Preference Alterations in a Choice Blindness Paradigm

PubMed Central

Taya, Fumihiko; Gupta, Swati; Farber, Ilya; Mullette-Gillman, O'Dhaniel A.

2014-01-01

Objectives It is commonly believed that individuals make choices based upon their preferences and have access to the reasons for their choices. Recent studies in several areas suggest that this is not always the case. In choice blindness paradigms, two-alternative forced-choice in which chosen-options are later replaced by the unselected option, individuals often fail to notice replacement of their chosen option, confabulate explanations for why they chose the unselected option, and even show increased preferences for the unselected-but-replaced options immediately after choice (seconds). Although choice blindness has been replicated across a variety of domains, there are numerous outstanding questions. Firstly, we sought to investigate how individual- or trial-factors modulated detection of the manipulations. Secondly, we examined the nature and temporal duration (minutes vs. days) of the preference alterations induced by these manipulations. Methods Participants performed a computerized choice blindness task, selecting the more attractive face between presented pairs of female faces, and providing a typewritten explanation for their choice on half of the trials. Chosen-face cue manipulations were produced on a subset of trials by presenting the unselected face during the choice explanation as if it had been selected. Following all choice trials, participants rated the attractiveness of each face individually, and rated the similarity of each face pair. After approximately two weeks, participants re-rated the attractiveness of each individual face online. Results Participants detected manipulations on only a small proportion of trials, with detections by fewer than half of participants. Detection rates increased with the number of prior detections, and detection rates subsequent to first detection were modulated by the choice certainty. We show clear short-term modulation of preferences in both manipulated and non-manipulated explanation trials compared to choice-only trials (with opposite directions of effect). Preferences were altered in the direction that subjects were led to believe they selected. PMID:25247886

Influence of Honey Bee Genotype and Wintering Method on Wintering Performance of Varroa destructor (Parasitiformes: Varroidae)-Infected Honey Bee (Hymenoptera: Apidae) Colonies in a Northern Climate.

PubMed

Bahreini, Rassol; Currie, Robert W

2015-08-01

The objective of this study was to assess the effectiveness of a cooperative breeding program designed to enhance winter survival of honey bees (Apis mellifera L.) when exposed to high levels of varroa (Varroa destructor Anderson and Trueman) in outdoor-wintered and indoor-wintered colonies. Half of the colonies from selected and unselected stocks were randomly assigned to be treated with late autumn oxalic acid treatment or to be left untreated. Colonies were then randomly assigned to be wintered either indoors (n = 37) or outdoors (n = 40). Late autumn treatment with oxalic acid did not improve wintering performance. However, genotype of bees affected colony survival and the proportion of commercially viable colonies in spring, as indicated by greater rates of colony survival and commercially viable colonies for selected stock (43% survived and 33% were viable) in comparison to unselected stock (19% survived and 9% were viable) across all treatment groups. Indoor wintering improved spring bee population score, proportion of colonies surviving, and proportion of commercially viable colonies relative to outdoor wintering (73% of selected stock and 41% of unselected stock survived during indoor wintering). Selected stock showed better "tolerance" to varroa as the selected stock also maintained higher bee populations relative to unselected stock. However, there was no evidence of "resistance" in selected colonies (reduced mite densities). Collectively, this experiment showed that breeding can improve tolerance to varroa and this can help minimize colony loss through winter and improve colony wintering performance. Overall, colony wintering success of both genotypes of bees was better when colonies were wintered indoors than when colonies were wintered outdoors. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Factors predisposing to consecutive esotropia after surgery to correct intermittent exotropia.

PubMed

Jang, Jung Hyun; Park, Jung Min; Lee, Soo Jung

2012-10-01

To investigate the incidence of and factors predisposing to consecutive esotropia after intermittent exotropia surgery, and to prevent the onset of consecutive esotropia. We retrospectively surveyed 226 patients who had been followed up for more than 1 year after surgery for intermittent exotropia conducted between February 2005 and September 2010. Consecutive esotropia was defined as an esotropia of at least 10 prism diopters (PD) at distance or near at least once in 2 weeks after surgery. Presumed risk factors for consecutive esotropia were analyzed. Gender, age at surgery, average binocular spherical equivalent, anisometropia, high myopia, amblyopia, preoperative angle of deviation, vertical deviation, A-V pattern strabismus, exotropia type, type of surgery, stereopsis, and suppression were investigated to evaluate factors influencing the onset of consecutive esotropia. Consecutive esotropia occurred in 22 patients (9.7 %). Significant correlations with occurrence of the condition were found with high myopia (P = 0.013), amblyopia (P = 0.047), preoperative angle of deviation of 25-40 PD at distance (P = 0.016), deviation at distance - deviation at near > 10 PD (P = 0.041), lateral incomitance (P = 0.007), tenacious proximal convergence fusion type (P = 0.001), unilateral lateral rectus muscle recession and medial rectus muscle resection (P = 0.001). High myopia, amblyopia, and lateral incomitance were predisposing factors for consecutive esotropia. Furthermore, the preoperative angle of deviation at distance, differences between the angle of deviation at near and at distance, the type of intermittent exotropia, and the type of surgery affected the incidence of consecutive esotropia. More attention must be paid to patients with such factors.

Factors related to elevated vaginal pH in the first trimester of pregnancy.

PubMed

Zodzika, Jana; Rezeberga, Dace; Jermakova, Irina; Vasina, Olga; Vedmedovska, Natalija; Donders, Gilbert

2011-01-01

To assess different bacterial and epidemiological factors associations with increased vaginal pH in the pregnant women population during the first trimester. A cross-sectional, observational study. Three outpatient clinics in Riga. From July 2009 until January 2010, 139 unselected consecutive pregnant women at the first prenatal visit. Pregnant women were submitted to an interview, vaginal examination and vaginal specimen collection for pH measurement and native microscopy. Vaginal pH ≥4.5 was considered as elevated. Abnormal bacterial microflora was classified according to Donders. Elevated vaginal pH was significantly associated with bacterial vaginosis (p < 0.001), aerobic vaginitis (p < 0.001) and mixed aerobic vaginitis and bacterial vaginosis flora (p < 0.001) and presence of sperm cells in the smears (p= 0.024). Most cases with sperm were associated with abnormal vaginal flora. Normal lactobacillary morphotypes were more often found in the pH ≤4.4 group (p < 0.001), while leptosomic and short types were found more frequently with increased pH. Elevated vaginal pH is associated with different types of abnormal vaginal flora and the presence of sperm cells. © 2010 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2010 Nordic Federation of Societies of Obstetrics and Gynecology.

Interest in genomic SNP testing for prostate cancer risk: a pilot survey.

PubMed

Hall, Michael J; Ruth, Karen J; Chen, David Yt; Gross, Laura M; Giri, Veda N

2015-01-01

Advancements in genomic testing have led to the identification of single nucleotide polymorphisms (SNPs) associated with prostate cancer. The clinical utility of SNP tests to evaluate prostate cancer risk is unclear. Studies have not examined predictors of interest in novel genomic SNP tests for prostate cancer risk in a diverse population. Consecutive participants in the Fox Chase Prostate Cancer Risk Assessment Program (PRAP) (n = 40) and unselected men from surgical urology clinics (n = 40) completed a one-time survey. Items examined interest in genomic SNP testing for prostate cancer risk, knowledge, impact of unsolicited findings, and psychosocial factors including health literacy. Knowledge of genomic SNP tests was low in both groups, but interest was higher among PRAP men (p < 0.001). The prospect of receiving unsolicited results about ancestral genomic markers increased interest in testing in both groups. Multivariable modeling identified several predictors of higher interest in a genomic SNP test including higher perceived risk (p = 0.025), indicating zero reasons for not wanting testing (vs ≥1 reason) (p = 0.013), and higher health literacy (p = 0.016). Knowledge of genomic SNP testing was low in this sample, but higher among high-risk men. High-risk status may increase interest in novel genomic tests, while low literacy may lessen interest.

Temporal trends in sperm count: a systematic review and meta-regression analysis.

PubMed

Levine, Hagai; Jørgensen, Niels; Martino-Andrade, Anderson; Mendiola, Jaime; Weksler-Derri, Dan; Mindlis, Irina; Pinotti, Rachel; Swan, Shanna H

2017-11-01

Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality. To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group. PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models. SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively). This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly Mutated Wnt/β-Catenin Pathway Associated with Oncogenic EGFR Mutations.

PubMed

Jiang, Jingrui; Protopopov, Alexei; Sun, Ruobai; Lyle, Stephen; Russell, Meaghan

2018-04-09

Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS)-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples. We found that activating EGFR mutations were predominantly detected in lung cancer, particularly in non-small cell lung cancer (NSCLC). The mutational landscape of EGFR-driven tumors covered most key signaling pathways and biological processes. Strikingly, the Wnt/β-catenin pathway was highly mutated (48 variants detected in 46% of the EGFR-driven tumors), and its variant number topped that in the TP53/apoptosis and PI3K-AKT-mTOR pathways. Furthermore, an analysis of mutation distribution revealed a differential association pattern of gene mutations between EGFR exon 19del and EGFR L858R. Our results confirm the aggressive nature of the oncogenic EGFR-driven tumors and reassure that a combinational strategy should have advantages over an EGFR-targeted monotherapy and holds great promise for overcoming drug resistance.

Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan

PubMed Central

Yamagishi, Hatsushi; Koike, Tomoyuki; Ohara, Shuichi; Kobayashi, Shigeyuki; Ariizumi, Ken; Abe, Yasuhiko; Iijima, Katsunori; Imatani, Akira; Inomata, Yoshifumi; Kato, Katsuaki; Shibuya, Daisuke; Aida, Shigemitsu; Shimosegawa, Tooru

2008-01-01

AIM: To examine the prevalence of gastroesophageal reflux disease (GERD) symptoms in a large unselected general population in Japan. METHODS: In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged > 40 years. A total of 160 983 Japanese (60 774 male, 100 209 female; mean age 61.9 years) who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 (34 275 male, 48 619 female; mean age 62.4 years) to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period. RESULTS: The respective prevalences of the symptoms in males and females were: heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year age group. Dysphagia was also significantly more frequent in female patients. CONCLUSION: The prevalence of typical GERD symptoms (heartburn) was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group. PMID:18322948

Germline EMSY sequence alterations in hereditary breast cancer and ovarian cancer families.

PubMed

Määttä, Kirsi M; Nurminen, Riikka; Kankuri-Tammilehto, Minna; Kallioniemi, Anne; Laasanen, Satu-Leena; Schleutker, Johanna

2017-07-24

BRCA1 and BRCA2 mutations explain approximately one-fifth of the inherited susceptibility in high-risk Finnish hereditary breast and ovarian cancer (HBOC) families. EMSY is located in the breast cancer-associated chromosomal region 11q13. The EMSY gene encodes a BRCA2-interacting protein that has been implicated in DNA damage repair and genomic instability. We analysed the role of germline EMSY variation in breast/ovarian cancer predisposition. The present study describes the first EMSY screening in patients with high familial risk for this disease. Index individuals from 71 high-risk, BRCA1/2-negative HBOC families were screened for germline EMSY sequence alterations in protein coding regions and exon-intron boundaries using Sanger sequencing and TaqMan assays. The identified variants were further screened in 36 Finnish HBOC patients and 904 controls. Moreover, one novel intronic deletion was screened in a cohort of 404 breast cancer patients unselected for family history. Haplotype block structure and the association of haplotypes with breast/ovarian cancer were analysed using Haploview. The functionality of the identified variants was predicted using Haploreg, RegulomeDB, Human Splicing Finder, and Pathogenic-or-Not-Pipeline 2. Altogether, 12 germline EMSY variants were observed. Two alterations were located in the coding region, five alterations were intronic, and five alterations were located in the 3'untranslated region (UTR). Variant frequencies did not significantly differ between cases and controls. The novel variant, c.2709 + 122delT, was detected in 1 out of 107 (0.9%) breast cancer patients, and the carrier showed a bilateral form of the disease. The deletion was absent in 897 controls (OR = 25.28; P = 0.1) and in 404 breast cancer patients unselected for family history. No haplotype was identified to increase the risk of breast/ovarian cancer. Functional analyses suggested that variants, particularly in the 3'UTR, were located within regulatory elements. The novel deletion was predicted to affect splicing regulatory elements. These results suggest that the identified EMSY variants are likely neutral at the population level. However, these variants may contribute to breast/ovarian cancer risk in single families. Additional analyses are warranted for rare novel intronic deletions and the 3'UTR variants predicted to have functional roles.

Item Selection, Evaluation, and Simple Structure in Personality Data

PubMed Central

Pettersson, Erik; Turkheimer, Eric

2010-01-01

We report an investigation of the genesis and interpretation of simple structure in personality data using two very different self-reported data sets. The first consists of a set of relatively unselected lexical descriptors, whereas the second is based on responses to a carefully constructed instrument. In both data sets, we explore the degree of simple structure by comparing factor solutions to solutions from simulated data constructed to have either strong or weak simple structure. The analysis demonstrates that there is little evidence of simple structure in the unselected items, and a moderate degree among the selected items. In both instruments, however, much of the simple structure that could be observed originated in a strong dimension of positive vs. negative evaluation. PMID:20694168

Role of rituximab in treatment of patients with primary central nervous system lymphoma: a retrospective analysis of the Czech lymphoma study group registry.

PubMed

Mocikova, Heidi; Pytlik, Robert; Sykorova, Alice; Janikova, Andrea; Prochazka, Vit; Vokurka, Samuel; Berkova, Adela; Belada, David; Campr, Vit; Buresova, Lucie; Trneny, Marek

2016-12-01

We have investigated whether the addition of rituximab to methotrexate, procarbazine, vincristine, radiotherapy and cytarabine was associated with improved outcome of primary central nervous system lymphomas (PCNSL). Of 164 patients, 49 received rituximab. Median age was 63 years, median Karnofsky performance score (KPS) was 60 and median follow-up of living patients was 59.5 months. 1- and 2-year PFS were 49.7 and 37.9%, 1- and 2-year OS were 57.0 and 45.3%. Median progression-free survival (PFS), but not overall survival (OS) was significantly better for patients treated with rituximab (22.9 vs. 10.9 months, p = 0.037). In multivariate analysis, age ≤70 years and KPS ≥90 were predictive for PFS and OS, rituximab was an independent prognostic factor for PFS only. In landmark analyses, rituximab was not found beneficial for long-term survivors and no group particularly benefited from rituximab. In conclusion, addition of rituximab was associated with improved PFS, but not OS in this unselected cohort of PCNSL patients.

Hospital Anxiety and Depression Scale: Factor Structure, Internal Consistency and Convergent Validity in Patients with Dizziness.

PubMed

Piker, Erin G; Kaylie, David M; Garrison, Douglas; Tucci, Debara L

2015-01-01

Psychiatric comorbidities, particularly anxiety-related pathologies, are often observed in dizzy patients. The Hospital Anxiety and Depression Scale (HADS) is a widely used self-report instrument used to screen for anxiety and depression in medical outpatient settings. The purpose of this study was to assess the factor structure, internal consistency and convergent validity of the HADS in an unselected group of patients with dizziness. The HADS and the Dizziness Handicap Inventory (DHI) were administered to 205 dizzy patients. An exploratory factor analysis was conducted and indicated a 3-factor structure, inconsistent with the 2-subscale structure (i.e. anxiety and depression) of the HADS. The total scale was found to be internally consistent, and convergent validity, as assessed using the DHI, was acceptable. Overall findings suggest that the HADS should not be used as a tool for psychiatric differential diagnosis, but rather as a helpful screener for general psychiatric distress in the two domains of psychiatric illness most germane in dizzy patients. © 2015 S. Karger AG, Basel.

Reporting Severe Hypoglycemia in Type 1 Diabetes: Facts and Pitfalls.

PubMed

Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2017-10-28

To describe potential factors influencing reporting of severe hypoglycemia in adult patients with type 1 diabetes and to analyze their effect on reported rates of severe hypoglycemia. Reported rates of severe hypoglycemia defined as need for third party assistance vary between 0.3-3.0 events per patient-year in unselected cohorts, corresponding to a yearly prevalence range of 10-53%. When defined as need for parenteral therapy with glucose or glucagon or need for admission to an emergency unit or hospitalization, incidence and prevalence rates of severe hypoglycemia are 0.02-0.5 events per patient-year and 1-29%, respectively. When subjects with recurrent severe hypoglycemia in the past or suffering from impaired hypoglycemia awareness are excluded from participation in studies, lower rates are reported. Studies applying anonymous reporting or reporting by partners report higher rates of severe hypoglycemia. There is a large variation between studies reporting incidence and prevalence of severe hypoglycemia in patients with type 1 diabetes, mainly explained by definition of severity, methods of reporting, and patient selection. These findings call for consensus about hypoglycemia definition and reporting in future research.

Transbulbar B-Mode Sonography in Multiple Sclerosis: Clinical and Biological Relevance.

PubMed

De Masi, Roberto; Orlando, Stefania; Conte, Aldo; Pasca, Sergio; Scarpello, Rocco; Spagnolo, Pantaleo; Muscella, Antonella; De Donno, Antonella

2016-12-01

Optic nerve sheath diameter quantification by transbulbar B-mode sonography is a recently validated technique, but its clinical relevance in relapse-free multiple sclerosis patients remains unexplored. In an open-label, comparative, cross-sectional study, we aimed to assess possible differences between patients and healthy controls in terms of optic nerve sheath diameter and its correlation with clinical/paraclinical parameters in this disease. Sixty unselected relapse-free patients and 35 matched healthy controls underwent transbulbar B-mode sonography. Patients underwent routine neurologic examination, brain magnetic resonance imaging and visual evoked potential tests. The mean optic nerve sheath diameter 3 and 5 mm from the eyeball was 22-25% lower in patients than controls and correlated with the Expanded Disability Status Scale (r = -0.34, p = 0.048, and r = -0.32, p = 0.042, respectively). We suggest that optic nerve sheath diameter quantified by transbulbar B-mode sonography should be included in routine assessment of the disease as an extension of the neurologic examination. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Relationship between consecutive deterioration of mean deviation value and progression of visual field defect in open-angle glaucoma.

PubMed

Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Takeda, Ryuji; Shiraga, Fumio

2015-01-01

To analyze the relationship between consecutive deterioration of mean deviation (MD) value and glaucomatous visual field (VF) progression in open-angle glaucoma (OAG), including primary OAG and normal tension glaucoma. The subjects of the study were patients undergoing treatment for OAG who had performed VF tests at least 10 times with a Humphrey field analyzer (SITA standard, C30-2 program). The VF progression was defined by a significantly negative MD slope (MD slope worsening) at the final VF test during the follow-up period. The relationship between the MD slope worsening and the consecutive deterioration of MD value were retrospectively analyzed. A total of 165 eyes of 165 patients were included in the analysis. Significant progression of VF defects was observed in 72 eyes of 72 patients (43.6%), while no significant progression was evident in 93 eyes of 93 patients (56.4%). There was significant relationship between the frequency of consecutive deterioration of MD value and MD slope worsening (P<0.0001, Cochran-Armitage trend test). A significant association was observed for MD slope worsening in the eyes with three (odds ratio: 2.1, P=0.0224) and four (odds ratio: 3.6, P=0.0008) consecutive deterioration of MD value in multiple logistic regression analysis, but no significant association in the eyes with two consecutive deterioration (odds ratio: 1.1, P=0.8282). The eyes with VF progression had significantly lower intraocular pressure reduction rate (P<0.01). This retrospective study has shown that three or more consecutive deterioration of MD value might be a predictor to future significant MD slope worsening in OAG.

Studies on strain sensitivity of Trichomonas vaginalis to metronidazole.

PubMed Central

Meingassner, J G; Havelec, L; Mieth, H

1978-01-01

Ninety-four strains of Trichomonas vaginalis isolated from unselected patients in Vienna during the period from November 1975 to November 1975 were subjected to sensitivity tests against metronidazole in vitro and in vivo. Nearly 90% of the isolates examined showed in vitro growth inhibition at concentrations of 0.4 to 1.6 microgram metronidazole/ml and only about 10% at concentrations of less than 0.4 microgram/ml. All isolates showed some inhibition of growth after incubation for 48 hours with 3.2 microgram metroidazole/ml. Tests on treatment carried out on experimentally infected mice revealed that all strains of T. vaginalis examined were sensitive to metronidazole (MDE: less than 3 x 35 mg/kg peroral). PMID:305807

Two consecutive twin and a singleton pregnancy in a patient with chronic myeloid leukemia.

PubMed

Halim, T A; Nabeel, N

2014-01-01

Consecutive multiple pregnancies with Chronic myeloid leukemia is a rare event and little is known about its prevalence and management with or without chemotherapy. We present a case of three consecutive pregnancies in a woman with CML, two of which were multiple pregnancies.

Dynamic self-regulating prosthesis (protesi autoregolantesi dinamica): the long-term results in the treatment of primary inguinal hernias.

PubMed

Valenti, Gabriele; Baldassarre, Emanuele; Testa, Alessandro; Arturi, Alessandro; Torino, Giovanni; Campisi, Costantino; Capuano, Giorgio

2006-03-01

The dynamic self-regulating prosthesis (protesi autoregolantesi dinamica, PAD) is a double-layered prosthesi, in use since 1992 in inguinal hernia repair. In 1999, we published the short-term results on 500 patients and herein we report the long-term follow-up. Five hundred eighty-five PAD procedures were performed on 500 adult male, unselected patients. Hernias were unilateral in 415 patients, were bilateral in 85 patients, were direct in 197 patients (33.7%), were indirect in 269 patients (46.0%), and were combined in 119 patients (20.3%). Four hundred sixty-four patients were alive at the follow-up period of minimum 5 years, whereas 36 died (7.2%) of causes unrelated to the hernia. No information was available on 73 patients (14.6%). Therefore, the follow-up was consisted of 391 patients (78.2%) with 469 hernias. The recurrence and testicular atrophy rates were nil. Three patients (0.77%) presented chronic pain and 18 (4.6%) suffered persistent discomfort or paresthesia. A hydrocoele was observed in one patient (0.2%). The long-term data confirm the efficacy of the dynamic self-regulating posthesis hernioplasty. We propose it as a standard of care in all cases of primary inguinal hernia in adult males, retaining it as a definitive and comfortable solution.

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: study by the Nagasaki CML Study Group.

PubMed

Itonaga, Hidehiro; Tsushima, Hideki; Imanishi, Daisuke; Hata, Tomoko; Doi, Yuko; Mori, Sayaka; Sasaki, Daisuke; Hasegawa, Hiroo; Matsuo, Emi; Nakashima, Jun; Kato, Takeharu; Horai, Makiko; Taguchi, Masataka; Matsuo, Masatoshi; Taniguchi, Hiroaki; Makiyama, Junnya; Sato, Shinya; Horio, Kensuke; Ando, Koji; Moriwaki, Yuji; Sawayama, Yasushi; Ogawa, Daisuke; Yamasaki, Reishi; Takasaki, Yumi; Imaizumi, Yoshitaka; Taguchi, Jun; Kawaguchi, Yasuhisa; Yoshida, Shinichiro; Joh, Tatsuro; Moriuchi, Yukiyoshi; Nonaka, Hiroaki; Soda, Hisashi; Fukushima, Takuya; Nagai, Kazuhiro; Kamihira, Shimeru; Tomonaga, Masao; Yanagihara, Katsunori; Miyazaki, Yasushi

2014-01-01

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Testicular tumours in prepubertal children: About eight cases.

PubMed

Khemakhem, Rachid; Ahmed, Yosra Ben; Jlidi, Said; Nouira, Faouzi; Fdhila, Faten; Charieg, Awatef; Ghorbel, Sofiene; Barsaoui, Sihem; Chaouachi, Béji

2013-01-01

To analyze the spectrum of testicular tumors in prepubertal children and the therapeutic resultants in an unselected population. Our hospital database was analyzed for testicular tumors from January 1995 to December 2010 concerning clinical presentation, treatment and therapeutic results. Eight patients were operated on because of testicular tumors. In six cases (75%) the tumor was benign: benign teratoma (four cases), epidermoid cyst (one case) and immature teratoma (one case). Two patients (25%) had a malignant tumour: yolk-sac tumour (two cases). All this children underwent surgery. Radical inguinal orchidectomy was performed in six cases and conservative surgery was performed in two cases. One patient has received adjuvant chemotherapy. Follow-up was uneventfully three years after primary surgery. In prepubertal children, most testicular tumours are benign. If tumour markers were negative testis-preserving surgery can be proposed, complete excision of the tumour should be ascertained. In the case of testicular teratoma, the possibility of contralateral tumour should be considered in the follow-up.

[Low-dose omega-3 fatty acids as lipid lowering agents in the practice. A field study of ambulatory patients in general practice].

PubMed

Zakaria, B; Bertsch, S

1992-04-10

BASICS: Clinical trials have shown that omega-3 fatty acids are also effective at smaller doses than those so far recommended for lowering lipid concentrations. Testing this finding in a large number of unselected outpatients. Open multicentric trial involving 197 patients with dyslipoproteinemia. Treatment comprised omega-3 fatty acids, 1.1 to 1.4 g per day administered for a period of 12 weeks. After 12 weeks of treatment, serum triglycerides decreased on average by about 23%, total cholesterol by about 10%, and LDL cholesterol by about 5%. HDL cholesterol rose by an average of 16%. The fish oil preparation (Eicosapen, Nycomed, Munich) was well tolerated; a fishy taste and mild gastrointestinal complaints led to discontinuation of treatment in only four cases. It was also found that the effect of omega-3 fatty acids was appreciably greater in hypertensives than in patients with normal blood pressure--not only on systolic and diastolic blood pressure, but also on serum triglycerides and HDL.

Novel drugs in clinical development for hepatocellular carcinoma.

PubMed

Waidmann, Oliver; Trojan, Jörg

2015-01-01

Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Within recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development either due to toxicity or lack of benefit. This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC. In unselected patients with advanced HCC, disappointing results have been reported from several large trials. However, in two subgroups encouraging results have been achieved. Treatment with the MET inhibitor tivantinib resulted in a substantial survival benefit in the subgroup of MET overexpressing tumors in a randomized Phase II trial. Furthermore, the vascular endothelial growth factor receptor 2 antibody ramucirumab resulted in improved overall survival in patients with baseline α-fetoprotein (AFP) ≥ 400 ng/ml in a Phase III trial. These two agents, and several others, will be further developed in HCC. Moreover, immunotherapeutics such as checkpoint inhibitors, programmed death receptor-1 blocking antibodies and oncolytic viruses are under investigation in advanced HCC.

Enhanced treatment of secondary municipal wastewater effluent: comparing (biological) filtration and ozonation in view of micropollutant removal, unselective effluent toxicity, and the potential for real-time control.

PubMed

Chys, Michael; Demeestere, Kristof; Ingabire, Ange Sabine; Dries, Jan; Van Langenhove, Herman; Van Hulle, Stijn W H

2017-07-01

Ozonation and three (biological) filtration techniques (trickling filtration (TF), slow sand filtration (SSF) and biological activated carbon (BAC) filtration) have been evaluated in different combinations as tertiary treatment for municipal wastewater effluent. The removal of 18 multi-class pharmaceuticals, as model trace organic contaminants (TrOCs), has been studied. (Biological) activated carbon filtration could reduce the amount of TrOCs significantly (>99%) but is cost-intensive for full-scale applications. Filtration techniques mainly depending on biodegradation mechanisms (TF and SSF) are found to be inefficient for TrOCs removal as a stand alone technique. Ozonation resulted in 90% removal of the total amount of quantified TrOCs, but a post-ozonation step is needed to cope with an increased unselective toxicity. SSF following ozonation showed to be the only technique able to reduce the unselective toxicity to the same level as before ozonation. In view of process control, innovative correlation models developed for the monitoring and control of TrOC removal during ozonation, are verified for their applicability during ozonation in combination with TF, SSF or BAC. Particularly for the poorly ozone reactive TrOCs, statistically significant models were obtained that correlate TrOC removal and reduction in UVA 254 as an online measured surrogate parameter.

Online attentional bias modification training targeting anxiety and depression in unselected adolescents: Short- and long-term effects of a randomized controlled trial.

PubMed

de Voogd, E L; Wiers, R W; Prins, P J M; de Jong, P J; Boendermaker, W J; Zwitser, R J; Salemink, E

2016-12-01

Based on information processing models of anxiety and depression, we investigated the efficacy of multiple sessions of online attentional bias modification training to reduce attentional bias and symptoms of anxiety and depression, and to increase emotional resilience in youth. Unselected adolescents (N = 340, age: 11-18 years) were randomly allocated to eight sessions of a dot-probe, or a visual search-based attentional training, or one of two corresponding placebo control conditions. Cognitive and emotional measures were assessed pre- and post-training; emotional outcome measures also at three, six and twelve months follow-up. Only visual search training enhanced attention for positive information, and this effect was stronger for participants who completed more training sessions. Symptoms of anxiety and depression reduced, whereas emotional resilience improved. However, these effects were not especially pronounced in the active conditions. Thus, this large-scale randomized controlled study provided no support for the efficacy of the current online attentional bias modification training as a preventive intervention to reduce symptoms of anxiety or depression or to increase emotional resilience in unselected adolescents. However, the absence of biased attention related to symptomatology at baseline, and the large drop-out rates at follow-up preclude strong conclusions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Consecutive rebounds in plasma viral load are associated with virological failure at 52 weeks among HIV-infected patients.

PubMed

Raboud, Janet M; Rae, Sandra; Woods, Ryan; Harris, Marianne; Montaner, Julio S G

2002-08-16

To describe the characteristics and predictors of transient plasma viral load (pVL) rebounds among patients on stable antiretroviral therapy and to determine the effect of one or more pVL rebounds on virological response at week 52. Individual data were combined from 358 patients from the INCAS, AVANTI-2 and AVANTI-3 studies. Logistic regression models were used to determine the relationship between the magnitude of an increase in pVL and the probability of returning to the lower limit of quantification (LLOQ: 20-50 copies/ml) and to determine the odds of virological success at 52 weeks associated with single and consecutive pVL rebounds. A group of 165 patients achieved a pVL nadir < LLOQ; of these, 85 patients experienced pVL rebounds within 52 weeks. The probability of a pVL rebound was greater among patients who did not adhere to treatment (68% vs 49%; P < 0.05). The probability of reachieving virological suppression after a pVL rebound was not associated with the magnitude of the rebound [odds ratio (OR), 0.86; P = 0.56] but was associated with triple therapy (OR, 2.22; P = 0.06) or non-adherence (OR, 0.40; P = 0.04). The probability of virological success at week 52 was not associated with an isolated pVL rebound but was less likely after detectable pVL at two consecutive visits. An isolated pVL rebound was not associated with virological success at 52 weeks but rebounds at two consecutive visits decreased the probability of later virological success. Given their high risk of short-term virological failure, patients who present with consecutive detectable pVL measurements following complete suppression should be considered ideal candidates for intervention studies.

Quantitative structural MRI for early detection of Alzheimer’s disease

PubMed Central

McEvoy, Linda K; Brewer, James B

2011-01-01

Alzheimer’s disease (AD) is a common progressive neurodegenerative disorder that is not currently diagnosed until a patient reaches the stage of dementia. There is a pressing need to identify AD at an earlier stage, so that treatment, when available, can begin early. Quantitative structural MRI is sensitive to the neurodegeneration that occurs in mild and preclinical AD, and is predictive of decline to dementia in individuals with mild cognitive impairment. Objective evidence of ongoing brain atrophy will be critical for risk/benefit decisions once potentially aggressive, disease-modifying treatments become available. Recent advances have paved the way for the use of quantitative structural MRI in clinical practice, and initial clinical use has been promising. However, further experience with these measures in the relatively unselected patient populations seen in clinical practice is needed to complete translation of the recent enormous advances in scientific knowledge of AD into the clinical realm. PMID:20977326

The role of randomized cluster crossover trials for comparative effectiveness testing in anesthesia: design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial.

PubMed

Spence, Jessica; Belley-Côté, Emilie; Lee, Shun Fu; Bangdiwala, Shrikant; Whitlock, Richard; LeManach, Yannick; Syed, Summer; Lamy, Andre; Jacobsohn, Eric; MacIsaac, Sarah; Devereaux, P J; Connolly, Stuart

2018-07-01

Increasingly, clinicians and researchers recognize that studies of interventions need to evaluate not only their therapeutic efficacy (i.e., the effect on an outcome in ideal, controlled settings) but also their real-world effectiveness in broad, unselected patient groups. Effectiveness trials inform clinical practice by comparing variations in therapeutic approaches that fall within the standard of care. In this article, we discuss the need for studies of comparative effectiveness in anesthesia and the limitations of individual patient randomized-controlled trials in determining comparative effectiveness. We introduce the concept of randomized cluster crossover trials as a means of answering questions of comparative effectiveness in anesthesia, using the design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial (Clinicaltrials.gov identifier NCT03053869).

Somatic mutations in the transcriptional corepressor gene BCORL1 in adult acute myelogenous leukemia.

PubMed

Li, Meng; Collins, Roxane; Jiao, Yuchen; Ouillette, Peter; Bixby, Dale; Erba, Harry; Vogelstein, Bert; Kinzler, Kenneth W; Papadopoulos, Nickolas; Malek, Sami N

2011-11-24

To further our understanding of the genetic basis of acute myelogenous leukemia (AML), we determined the coding exon sequences of ∼ 18 000 protein-encoding genes in 8 patients with secondary AML. Here we report the discovery of novel somatic mutations in the transcriptional corepressor gene BCORL1 that is located on the X-chromosome. Analysis of BCORL1 in an unselected cohort of 173 AML patients identified a total of 10 mutated cases (6%) with BCORL1 mutations, whereas analysis of 19 AML cell lines uncovered 4 (21%) BCORL1 mutated cell lines. The majority (87%) of the mutations in BCORL1 were predicted to inactivate the gene product as a result of nonsense mutations, splice site mutation, or out-of-frame insertions or deletions. These results indicate that BCORL1 by genetic criteria is a novel candidate tumor suppressor gene, joining the growing list of genes recurrently mutated in AML.

[Evaluation of DCA vantage for rapid in-clinic measurement of HbA1c on capillary blood in young type 1 diabetic patients].

PubMed

El Arabi, H; Willems, D; Mélot, C; Dorchy, H

2013-01-01

Rapid in clinic measurement of glycated hemoglogin (HbA1c) allows to determine the level of metabolic control within a few minutes on capillary blood. We have evaluated the new DCA Vantage (Siemens) based on an immunological technique, replacing the DCA 2000+ (Siemens). The study included 120 unselected young type 1 diabetic patients, with different degrees of metabolic control. The DCA Vantage was compared with the HPLC system (Menarini HA 8160) whose deviation from the DCCT was < 0.1% across the clinical range. The mean underestimation of the DCA Vantage was -0.40%. The agreement limits (+/- 1.96 SD) were between 0.14% and -0.93%; this means +/- 0.53% around -0.40%. In conclusion, the DCA Vantage underestimates HbA1c levels; however it met the acceptance criteria of having a coefficient of variation < 3%.

Distinguishing rational from irrational applications of pharmacogenetic synergies from the bench to clinical trials.

PubMed

Hucl, Tomas; Gallmeier, Eike; Kern, Scott E

2007-06-01

Single therapeutic agents very often fail in unselected patients. It is therefore commonplace to combine an agent specifically with a selected patient subgroup or with another agent. To support such efforts, it is useful to clarify the distinctions between the terms and the mathematical models used in analyzing combinations. To incorporate molecular disease classifications, the familiar concept of the therapeutic window is modified to define a pharmacogenetic window, which is an unambiguous numerical measure of the magnitude of interaction produced by a combination, and to define a test of pharmacogenetic synergy. In contrast, certain common comparative methods, such as vertical windows (comparing effects at a given dose) and animal models of mutational targets may be dominated by undesirable features. Although this discussion is oriented towards cancer therapy, an extension of these concepts to other comparative biologic assays is feasible and advisable.

Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

PubMed

Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

2016-04-01

With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

Long-term safety and real-world effectiveness of fingolimod in relapsing multiple sclerosis

PubMed Central

Druart, Charlotte; El Sankari, Souraya; van Pesch, Vincent

2018-01-01

With a growing number of disease-modifying therapies becoming available for relapsing multiple sclerosis, there is an important need to gather real-world evidence data regarding long-term treatment effectiveness and safety in unselected patient populations. Although not providing as high a level of evidence as randomized controlled trials, and prone to bias, real-world studies from observational studies or registries nevertheless provide crucial information on real-world outcomes of a given therapy. In addition, evaluation of treatment satisfaction and impact on quality of life are increasingly regarded as complementary outcome measures. Fingolimod was the first oral disease-modifying therapy approved for relapsing multiple sclerosis. This review aims to summarize current knowledge on the long-term effectiveness and safety outcomes of multiple sclerosis patients on fingolimod. Impact on treatment satisfaction and quality of life will be discussed according to available data. PMID:29317850

Follicular flushing during oocyte retrieval: a systematic review and meta-analysis.

PubMed

Roque, Matheus; Sampaio, Marcos; Geber, Selmo

2012-11-01

The purpose of this systematic review and meta-analysis was to examine the literature and identify randomized controlled trials (RCTs), in order to answer if performing follicular flushing during the oocyte retrieval may improve the assisted reproductive technologies (ART) outcomes. An exhaustive electronic search was performed using MEDLINE and EMBASE databases. Only RCTs comparing follicular flushing to aspiration only during ART, were included. We included 5 trials, with a total of 482 patients randomized, with median ages ranging from 30.5 to 37.1. The data analyses did not show significant differences regarding live birth rate, clinical pregnancies rates, and the number of oocytes retrieved. The duration of oocyte retrieval was significantly increased in the follicular flushing group. The results from this systematic review and meta-analysis suggest that there is no advantage to use of routine follicular flushing during OR in an unselected group of patients.

Stent thrombosis and bleeding complications after implantation of sirolimus-eluting coronary stents in an unselected worldwide population: a report from the e-SELECT (Multi-Center Post-Market Surveillance) registry.

PubMed

Urban, Philip; Abizaid, Alexandre; Banning, Adrian; Bartorelli, Antonio L; Baux, Ana Cebrian; Džavík, Vladimír; Ellis, Stephen; Gao, Runlin; Holmes, David; Jeong, Myung Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Spaulding, Christian; Worthley, Stephen

2011-03-29

The aim of this study was to ascertain the 1-year incidence of stent thrombosis (ST) and major bleeding (MB) in a large, unselected population treated with sirolimus-eluting stents (SES). Stent thrombosis and MB are major potential complications of drug-eluting stent implantation. Their relative incidence and predisposing factors among large populations treated worldwide are unclear. The SES were implanted in 15,147 patients who were entered in a multinational registry. We analyzed the incidence of: 1) definite and probable ST as defined by the Academic Research Consortium; and 2) MB, with the STEEPLE (Safety and efficacy of Enoxaparin in PCI) definition, together with their relation to dual antiplatelet therapy (DAPT) and to 1-year clinical outcomes. The mean age of the sample was 62 ± 11 years, 30.4% were diabetic, 10% had a Charlson comorbidity index ≥3, and 44% presented with acute coronary syndrome or myocardial infarction. At 1 year, the reported compliance with DAPT as recommended by the European Society of Cardiology guidelines was 86.3%. Adverse event rates were: ST 1.0%, MB 1.0%, mortality 1.7%, myocardial infarction 1.9%, and target lesion revascularization 2.3%. Multivariate analysis identified 9 correlates of ST and 4 correlates of MB. Advanced age and a high Charlson index were associated with an increased risk of both ST and MB. After ST, the 7-day and 1-year all-cause mortality was 30% and 35%, respectively, versus 1.5% and 10% after MB. Only 2 of 13,749 patients (0.015%) experienced both MB and ST during the entire 1-year follow-up period. In this worldwide population treated with ≥1 SES, the reported compliance with DAPT was good, and the incidence of ST and MB was low. Stent thrombosis and MB very rarely occurred in the same patient. (The e-SELECT Registry: a Multicenter Post-Market Surveillance; NCT00438919). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Specific IgG4 antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis.

PubMed

Schuyler, Alexander J; Wilson, Jeffrey M; Tripathi, Anubha; Commins, Scott P; Ogbogu, Princess U; Kruzsewski, Patrice G; Barnes, Barrett H; McGowan, Emily C; Workman, Lisa J; Lidholm, Jonas; Rifas-Shiman, Sheryl L; Oken, Emily; Gold, Diane R; Platts-Mills, Thomas A E; Erwin, Elizabeth A

2018-04-18

Allergen-specific IgG 4 (sIgG 4 ) antibodies are often associated with tolerance, but sIgG 4 antibodies to causally relevant foods have been reported recently in adults with eosinophilic esophagitis (EoE). Prevalence and levels of food sIgG 4 are not well established in the general pediatric population. We sought to investigate serum food sIgG 4 with component diagnostics in children with EoE and children from an unselected birth cohort and to explore the effects of sex, age, and milk consumption on sIgG 4 levels. Sera from 71 pediatric patients with EoE and 210 early adolescent children from an unselected birth cohort (Project Viva) were assayed for sIgG 4 and specific IgE (sIgE) to major cow's milk (CM) proteins (α-lactalbumin, β-lactoglobulin, and caseins) and to wheat, soy, egg, and peanut proteins. In the EoE cohort high-titer sIgG 4 (≥10 μg/mL) to CM proteins was more common than in control sera and achieved odds ratios for EoE ranging from 5.5 to 8.4. sIgE levels to CM proteins were mostly 4 IU/mL or less in patients with EoE, such that sIgG 4 /sIgE ratios were often 10,000 or greater. When adjusted for age and milk consumption, high-titer sIgG 4 to CM proteins was strongly associated with EoE, with an odds ratio of greater than 20 to all 3 CM proteins in boys. sIgG 4 to CM proteins are common and high titer in children with EoE. Although it is not clear that this response is pathogenic, sIgG 4 levels imply that these antibodies are an important feature of the local immune response that gives rise to EoE. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Molecular genetic markers for thyroid FNAB. Established assays and future perspective.

PubMed

Musholt, Thomas J; Musholt, P B

2015-01-01

Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18-65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Comparison of two types of dipsticks to measure vaginal pH in clinical practice.

PubMed

Donders, Gilbert G G; Caeyers, Tinne; Tydhof, Priska; Riphagen, Ine; van den Bosch, Thierry; Bellen, Gert

2007-10-01

To assess the practical use of two dispsticks for measuring vaginal pH with a range 4-7 (Merck and Macherey Nagel in the diagnosis of vaginal infections. Routine gynaecological clinic in the General Hospital H Hart in Tienen and vulvo-vaginitis clinic in the University Hospital Gasthuisberg in Leuven, Belgium. After oral consent was obtained, 101 unselected consecutive women presenting for gynaecologic examination between 15 January 2004 and 15 February 2004 were included in an observational study. Vaginal smears were taken from the upper vaginal wall for pH measurement and for fresh wet mount examination by phase contrast microscopy for diagnosing lactobacillary grades and presence of pathogens. The observed color change of two different pH strips were compared with the color scale provided by the company by a junior investigator who was not familiar with the technique, nor with the pathology of the patient. The difficulty of the measurement was scored semi-quantitatively by assessing the time and effort necessary to decide on the correct pH. Using the Macherey-Nagel method, the mean pH score was lower in women with normal flora and in women with vaginal infections than when the Merck method was used, but the difference was not significant. The pH became progressively more abnormal with increasing lactobacillary grades, a correlation that was similar for both tests. The reading of the pH sticks was significantly simpler and quicker with Macherey-Nagel than with Merck. Although difficult readings with Merck strips were four times more frequent in the group of women with abnormal flora than in women with normal flora, this difference was not significant. (1) In both tests (Macherey-Nagel and Merck) the pH was more abnormal (higher) with increasing lactobacillary grades (declining number of lactobacillary morphotypes). (2) The Macherey-Nagel sticks are more user-friendly than Merck's.

Prevalence of ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms in Brazilian breast cancer-unaffected women

PubMed Central

Giacomazzi, J.; Aguiar, E.; Palmero, E.I.; Schmidt, A.V.; Skonieski, G.; Filho, D.D.; Bock, H.; Saraiva-Pereira, M.L.; Ewald, I.P.; Schuler-Faccini, L.; Camey, S.A.; Caleffi, M.; Giugliani, R.; Ashton-Prolla, P.

2012-01-01

Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease. PMID:22584640

Does anatomy of the pubic arch interfere with the maintaining of erection?

PubMed

Paul, Jean François; Virag, Ronald

2013-03-01

There are men who suffer from unsustainable erections without any identified cause of erectile dysfunction, raising the question if anatomical alterations could be involved. Since early anatomical studies, it has been proposed that to achieve full penile rigidity, the blood must be blocked inside the penis by compression of the deep dorsal vein (DDV), the main venous collector under pubic symphysis. Using a recently developed caverno computed tomography (CT) scan technique, allowing the evaluation of the venous drainage of the corpora cavernosa (CC) during erection, we have studied some anatomical conditions of this important part of the erectile phenomenon. Puboischial rami angles were measured in axial CT images and calculated strictly on the upper insertion point of the CC, using axial submillimeter slices in 37 patients divided into 3 groups depending on the results of the caverno CT scan: (i) no leak; (ii) superficial veins leaking; and (iii) drainage through the DDV and/or preprostatic plexus. In addition same angles were measured in two randomly unselected populations of men (N = 30), and women (N = 23) who underwent pelvic CT scan for various reasons, unrelated to their sexual or genital condition. The angles made by both puboischial rami were measured in patients with and without veno-occlusive dysfunction and in unselected samples of men and women. There is a significantly wider angle made by both puboischial rami in men without complete erection and without evidence of anomalous venous drainage (group 3) (72.2° ± 4.7° standard deviation [SD]), compared with both men with normal erection (group 1) (57.5 ± 5° SD) P < 0.00001, and men with incomplete erection and evidence of anomalous drainage (group 2) (57.7 ± 6° SD) P < 0.00001. If confirmed in larger samples, these results raise new questions on the mechanism and the role of these significant anatomical variations, yet unknown, in maintaining or not full rigid erections. © 2012 International Society for Sexual Medicine.

The effects of armodafinil on objective sleepiness and performance in a shift work disorder sample unselected for objective sleepiness.

PubMed

Howard, Ryan; Roth, Thomas; Drake, Christopher L

2014-06-01

Armodafinil is a medication used to treat excessive sleepiness in individuals with shift work disorder (SWD). In the present study, we investigate whether armodafinil can normalize nocturnal sleepiness in a group of typical SWD patients. Participants were 12 night workers (aged 33.8 ± 8.57 years, 7 female subjects) with excessive sleepiness (≥10 on the Epworth Sleepiness Scale; mean, 14.8 ± 3.16), meeting the International Classification of Sleep Disorders, Second Edition criteria for SWD, with no other sleep or medical disorders verified by polysomnogram. The multiple sleep latency test (MSLT) was not used as an entry criteria. Armodafinil was administered at 10:30 pm in a randomized, double-blind, placebo-controlled, crossover design with experimental nights separated by 1 week. Primary end point was the MSLT, with naps at 1:30, 3:30, 5:30, and 7:30 am. Other study measures included a sleepiness-alertness visual analog scale administered before each nap, and 2 computer-based performance tests evaluating attention and memory. Subjects with SWD had a mean MSLT of 5.3 ± 3.25 minutes, indicating a mean level of pathological sleepiness. Armodafinil significantly improved MSLT score to 11.1 ± 4.79 minutes (P = 0.006). Subjective levels of alertness on the visual analog scale also improved (P = 0.008). For performance, reaction time to central (P = 0.006) and peripheral (P = 0.003) stimuli and free recall memory (P = 0.05) were also improved. Armodafinil 150 mg administered at the beginning of a night shift normalizes nocturnal sleepiness in individuals with SWD unselected for objective sleepiness. Subjective measures of sleepiness and cognitive performance are also improved. This suggests that armodafinil can improve levels of nocturnal alertness to within normal daytime levels in the majority of patients with SWD.

Identification of men with low-risk biopsy-confirmed prostate cancer as candidates for active surveillance.

PubMed

Lin, Daniel W; Crawford, E David; Keane, Thomas; Evans, Brent; Reid, Julia; Rajamani, Saradha; Brown, Krystal; Gutin, Alexander; Tward, Jonathan; Scardino, Peter; Brawer, Michael; Stone, Steven; Cuzick, Jack

2018-06-01

A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10 -5 ). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. Copyright © 2018 Elsevier Inc. All rights reserved.

Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis: A Systematic Review and Meta-Analysis

PubMed Central

Kunutsor, Setor K.; Whitehouse, Michael R.; Blom, Ashley W.; Beswick, Andrew D.

2015-01-01

Background The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain. Objective To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome. Design Systematic review and meta-analysis. Data Sources MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators. Study Selection Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified. Review Methods Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics. Results In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0–10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2–9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies. Conclusion Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual participant data. Systematic Review Registration PROSPERO 2015: CRD42015016559 PMID:26407003

A prospective assessment of cytomegalovirus infection in active inflammatory bowel disease.

PubMed

de Saussure, P; Lavergne-Slove, A; Mazeron, M-C; Alain, S; Matuchansky, C; Bouhnik, Y

2004-12-01

The prevalence and clinical significance of cytomegalovirus infection is reportedly high in patients with refractory inflammatory bowel disease but is unknown in unselected patients with active disease. In patients admitted for active inflammatory bowel disease, we prospectively studied the presence and significance of cytomegalovirus infection using anti-cytomegalovirus antibodies, cytomegalovirus viraemia and antigenaemia and cytomegalovirus inclusions and cytomegalovirus immunochemistry staining in ileocolonic biopsies. A total of 64 patients were included (ulcerative colitis, n = 23; Crohn's disease, n = 41), 18 of whom had been on high-dose oral steroids and 11 on immunosuppressants. Anti-cytomegalovirus IgG and IgM were positive in 42 (66%) and 3 (5%) patients respectively. Blood or urine cytomegalovirus replication markers were found in 4 (6%) patients, all of whom had ulcerative colitis. Three patients had cytomegalovirus viraemia and received anti-viral treatment with ganciclovir. Only one of these patients had cytomegalovirus antigenaemia and also associated biopsy-proven cytomegalovirus colitis, probably as a primary cytomegalovirus infection. This patient is the only one who benefitted from anti-viral therapy. Cytomegalovirus infection is infrequent in in-patients with active inflammatory bowel disease. Systematic search of cytomegalovirus replication markers should not be performed. Isolated viraemia without associated antigenaemia or direct demonstration of cytomegalovirus in ileocolonic biopsies does not warrant anti-viral therapy.

Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin.

PubMed

Rubini Giménez, Maria; Hoeller, Rebeca; Reichlin, Tobias; Zellweger, Christa; Twerenbold, Raphael; Reiter, Miriam; Moehring, Berit; Wildi, Karin; Mosimann, Tamina; Mueller, Mira; Meller, Bernadette; Hochgruber, Thomas; Ziller, Ronny; Sou, Seoung Mann; Murray, Karsten; Sakarikos, Konstantin; Ernst, Susanne; Gea, Joaquim; Campodarve, Isabel; Vilaplana, Carles; Haaf, Philip; Steuer, Stephan; Minners, Jan; Osswald, Stefan; Mueller, Christian

2013-10-09

We examined whether undetectable levels of high-sensitivity cardiac Troponin (hs-cTn) can be used to rule out acute myocardial infarction (AMI) with a single blood draw at presentation to the emergency department (ED). In a prospective multicenter study we used 4 different hs-cTn assays (hs-cTnT Roche, and hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting with acute chest pain. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs-cTnT levels. Mean follow up was 24 months. Among 2072 consecutive patients with available hs-cTnT levels, 21% had an adjudicated diagnosis of AMI. Among AMI patients, 98.2% had initially detectable levels of hs-cTnT (sensitivity 98.2%, 95%CI 96.3%-99.2%, negative predictive value (NPV) 98.6%, 95%CI 97.0%-99.3%). Undetectable levels of hs-cTnT ruled out AMI in 26.5% of patients at presentation. The NPV was similar with the three hs-cTnI assays: among 1180 consecutive patients with available hs-cTnI (Siemens), the NPV was 98.8%; among 1151 consecutive patients with available hs-cTnI (Beckman Coulter), the NPV was 99.2%; among 1567 consecutive patients with available hs-cTnI (Abbott), the NPV was 100.0%. The percentage of patients with undetectable levels of hs-cTnI was similar among the three hs-cTnI assays and ranged from 11.4% to 13.9%. Undetectable levels of hs-cTn at presentation have a very high NPV and seem to allow the simple and rapid rule out of AMI. This criteria applies to much more patients with hs-TnT as compared to the investigated hs-cTnI assays. © 2013.

Are treatment results for eating disorders affected by ADHD symptoms? A one-year follow-up of adult females.

PubMed

Svedlund, Nils Erik; Norring, Claes; Ginsberg, Ylva; von Hausswolff-Juhlin, Yvonne

2018-05-02

To explore the influence of self-reported Attention Deficit Hyperactivity Disorder (ADHD) symptoms on recovery rate at 1-year follow-up in an unselected group of patients in a specialized eating disorder (ED) clinic. Four hundred forty-three adult females with an ED were assessed with the ADHD Self-Report Scale for Adults (ASRS-screener), and for demographic variables and ED symptoms. Recovery was registered at 1-year follow-up. A high degree of ADHD symptoms at baseline was predictive for nonrecovery of ED at 1-year follow-up in patients with loss of control over eating, bingeing, or purging. The presence of inattentive ADHD symptoms was stronger associated with nonrecovery than hyperactive/impulsive symptoms. A high degree of ADHD symptoms may have a negative impact on recovery in ED. Screening/diagnostic evaluation of ADHD in all loss of control over eating/bingeing/purging ED patients and studies of the effect of implementing ADHD-treatment strategies in this patient group are recommended. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.

A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors.

PubMed

Andersen, N S; Jensen, M K; de Nully Brown, P; Geisler, C H

2002-02-01

This study presents the first large clinical analysis of 105 unselected mantle cell lymphoma (MCL) patients diagnosed from 1992 to 2000 in a well-defined Danish population. The annual incidences were 0.7/100000 for men and 0.2/100000 for women, with no significant change during the study period. Of 97 evaluable cases, 43% achieved a complete response (CR) after initial therapy. The median disease-free (DFS) and overall survival (OS) rates were 15 and 30 months, respectively. In multivariate analysis, splenomegaly (P=0.002), anaemia (P=0.0001) and age (P=0.002), but not the international prognostic index (IPI) and the Ann Arbor staging system, had an independent impact on survival. Moreover, in a sub-analysis of 45 younger MCL patients (<65 years), a trend towards an OS plateau of 58% was observed in cases without splenomegaly and anaemia (n=29). Thus, in contrast to previously suggested prognostic factors, these variables may prove useful for clinical decisions in a significant subset of MCL patients.

A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS).

PubMed

Nacu, Aliona; Kvistad, Christopher E; Logallo, Nicola; Naess, Halvor; Waje-Andreassen, Ulrike; Aamodt, Anne Hege; Solhoff, Ragnar; Lund, Christian; Tobro, Håkon; Rønning, Ole Morten; Salvesen, Rolf; Idicula, Titto T; Thomassen, Lars

2015-07-11

Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients. Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue®) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0-1 at 90 days. NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given ≤ 4(½) hours after stroke onset in an unselected acute ischaemic stroke population eligible or not eligible for intravenous thrombolysis, with or without a defined arterial occlusion on CTA. If a positive effect and safety can be proven, contrast enhanced ultrasound treatment will be an option for all acute ischaemic stroke patients. EudraCT No 201200032341; www.clinicaltrials.gov NCT01949961.

Self-Cutting: Patient Characteristics Compared with Self-Poisoners

ERIC Educational Resources Information Center

Hawton, Keith; Harriss, Louise; Simkin, Sue; Bale, Elizabeth; Bond, Alison

2004-01-01

A large (n = 14,892) consecutive sample of deliberate self-harm (attempted suicide) patients who presented to a general hospital in the United Kingdom during a 23-year study period was examined (over two consecutive time periods) in order to compare the characteristics of those who used self-cutting (n = 428) and those who self-poisoned (n =…

Use of Diuretics is not associated with mortality in patients admitted to the emergency department: results from a cross-sectional study.

PubMed

Haider, Dominik G; Lindner, Gregor; Wolzt, Michael; Leichtle, Alexander Benedikt; Fiedler, Georg-Martin; Sauter, Thomas C; Fuhrmann, Valentin; Exadaktylos, Aristomenis K

2016-02-01

Patients with diuretic therapy are at risk for drug-induced adverse reactions. It is unknown if presence of diuretic therapy at hospital emergency room admission is associated with mortality. In this cross sectional analysis, all emergency room patients 2010 and 2011 at the Inselspital Bern, Switzerland were included. A multivariable logistic regression model was performed to assess the association between pre-existing diuretic medication and 28 day mortality. Twenty-two thousand two hundred thirty-nine subjects were included in the analysis. A total of 8.5%, 2.5%, and 0.4% of patients used one, two, or three or more diuretics. In univariate analysis spironolactone, torasemide and chlortalidone use were associated with 28 day mortality (all p < 0.05). In a multivariate cox regression model no association with mortality was detectable (p > 0.05). No difference existed between patients with or without diuretic therapy (P > 0.05). Age and creatinine were independent risk factors for mortaliy (both p < 0.05). Use of diuretics is not associated with mortality in an unselected cohort of patients presenting in an emergency room.

Diclofenac Does Not Reduce the Risk of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Low-Risk Units.

PubMed

Rainio, Mia; Lindström, Outi; Udd, Marianne; Louhimo, Johanna; Kylänpää, Leena

2017-08-01

Nonsteroidal anti-inflammatory drugs have an inhibitory role in pathogenesis of pancreatitis. Guidelines from the European Society of Gastrointestinal Endoscopy recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP for all patients without contraindications. Our aim was to evaluate the effect of diclofenac in preventing post-ERCP pancreatitis (PEP) in a high-volume, low-PEP-risk ERCP unit. The rate and severity of PEP were compared in groups of 1000 historical controls prior to the routine use of diclofenac and in 1000 patients receiving 100 mg diclofenac before ERCP. PEP occurred in 56 (2.8%) of the 2000 patients, and the rate of the pancreatitis was 2.8% in control group and 2.8% in diclofenac group (p = 1.000). The PEP rate among the native papilla patients was 3.9% in control group and 3.6% in diclofenac group (p = 0.803). In subgroup analysis of patients with a high risk of PEP, diclofenac neither prevented PEP nor made its course milder. In an unselected patient population in a center with a low incidence of PEP, diclofenac seems to have no beneficial effect.

Stereotactic Radiosurgery versus Natural History in Patients with Growing Vestibular Schwannomas.

PubMed

Tu, Albert; Gooderham, Peter; Mick, Paul; Westerberg, Brian; Toyota, Brian; Akagami, Ryojo

2015-08-01

Objective To describe our experience with stereotactic radiosurgery and its efficacy on growing tumors, and then to compare this result with the natural history of a similar cohort of non-radiation-treated lesions. Study Design A retrospective chart review and cohort comparison. Methods The long-term control rates of patients having undergone radiosurgery were collected and calculated, and this population was then compared with a group of untreated patients from the same period of time with growing lesions. Results A total of 61 patients with growing vestibular schwannomas treated with radiosurgery were included. After a mean of 160 months, we observed a control rate of 85.2%. When compared with a group of 36 patients with growing tumors who were yet to receive treatment (previously published), we found a corrected control rate or relative risk reduction of only 76.8%. Conclusion Radiosurgery for growing vestibular schwannomas is less effective than previously reported in unselected series. Although radiosurgery still has a role in managing this disease, consideration should be given to the actual efficacy that may be calculated when the natural history is known. We hope other centers will similarly report their experience on this cohort of patients.

Stereotactic Radiosurgery versus Natural History in Patients with Growing Vestibular Schwannomas

PubMed Central

Tu, Albert; Gooderham, Peter; Mick, Paul; Westerberg, Brian; Toyota, Brian; Akagami, Ryojo

2015-01-01

Objective To describe our experience with stereotactic radiosurgery and its efficacy on growing tumors, and then to compare this result with the natural history of a similar cohort of non-radiation–treated lesions. Study Design A retrospective chart review and cohort comparison. Methods The long-term control rates of patients having undergone radiosurgery were collected and calculated, and this population was then compared with a group of untreated patients from the same period of time with growing lesions. Results A total of 61 patients with growing vestibular schwannomas treated with radiosurgery were included. After a mean of 160 months, we observed a control rate of 85.2%. When compared with a group of 36 patients with growing tumors who were yet to receive treatment (previously published), we found a corrected control rate or relative risk reduction of only 76.8%. Conclusion Radiosurgery for growing vestibular schwannomas is less effective than previously reported in unselected series. Although radiosurgery still has a role in managing this disease, consideration should be given to the actual efficacy that may be calculated when the natural history is known. We hope other centers will similarly report their experience on this cohort of patients. PMID:26225318

Proteomic analysis of saliva: a unique tool to distinguish primary Sjögren's syndrome from secondary Sjögren's syndrome and other sicca syndromes

PubMed Central

2011-01-01

Introduction A growing interest has arisen in salivary proteomics as a tool for the identification of biomarkers for primary Sjögren's syndrome (pSS). Nonetheless, only a limited number of preclinical validation studies have been performed, limiting the possibility of translating proteomic results into clinical practice. The primary aim of this study was to refine the diagnostic power of a panel of candidate salivary biomarkers described in pSS with respect to both healthy volunteers and pathological controls. We also explored the pathogenetic function of the detected putative biomarkers both in the local exocrinopathy and in the systemic inflammatory processes of SS. Methods One hundred and eighty patients were included in the study overall. In the first "exploratory phase", we enrolled 40 females with pSS, 40 sex- and age-matched healthy volunteers, 10 patients with sicca non-SS and 15 secondary SS (sSS) patients. The testing cohort of the second "challenge phase" of the study was represented by 75 unselected, consecutive subjects: 19 pSS, 21 healthy volunteers, 10 sicca non-SS and 25 sSS patients. Salivary proteomic analysis was performed combining two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). Western blot (WB) analysis and enzyme-linked immunosorbent assay (ELISA) were employed to validate 2DE results. Ingenuity Pathway Analysis (IPA) Knowledge base was adopted to associate candidate biomarkers in a signalling pathogenetic network. Results A total of 28, 6, 7 and 12 protein spots were found to be significantly different in pSS samples with respect to healthy volunteers, non-SS sicca syndrome, SSc-sSS and rheumatoid arthritis-sSS, leading to the identification of 15 differently expressed proteins. Among them, α-amylases precursor, carbonic anhydrase VI, β-2 microglobulin, glyceraldehydes-3-phosphate dehydrogenase (G3PDH), epidermal fatty acid binding protein (E-FABP) and immunoglobulin k light chain (IGK-light chain) apparently showed the most significant differences in pSS when compared to healthy volunteers and non-SS pathological controls. On the other hand, as expected, pSS and sSS salivary profiles shared a great number of similarities. Conclusions This study demonstrated that salivary fluid might represent a novel ideal milieu for the detection of a diagnostic panel of candidate biomarkers for pSS, and to gain an insight into the pathogenetic processes underlying glandular and systemic autoimmune disorders. PMID:22117835

Persistence of nondysplastic Barrett's esophagus identifies patients at lower risk for esophageal adenocarcinoma: results from a large multicenter cohort.

PubMed

Gaddam, Srinivas; Singh, Mandeep; Balasubramanian, Gokulakrishnan; Thota, Prashanthi; Gupta, Neil; Wani, Sachin; Higbee, April D; Mathur, Sharad C; Horwhat, John D; Rastogi, Amit; Young, Patrick E; Cash, Brooks D; Bansal, Ajay; Vargo, John J; Falk, Gary W; Lieberman, David A; Sampliner, Richard E; Sharma, Prateek

2013-09-01

Recent population-based studies have shown a low risk of esophageal adenocarcinoma (EAC) in patients with nondysplastic Barrett's esophagus (NDBE). We evaluated whether persistence of NDBE over multiple consecutive surveillance endoscopic examinations could be used in risk stratification of patients with Barrett's esophagus (BE). We performed a multicenter outcomes study of a large cohort of patients with BE. Based on the number of consecutive surveillance endoscopies showing NDBE, we identified 5 groups of patients. Patients in group 1 were found to have NDBE at their first esophagogastroduodenoscopy (EGD). Patients in group 2 were found to have NDBE on their first 2 consecutive EGDs. Similarly, patients in groups 3, 4, and 5 were found to have NDBE on 3, 4, and 5 consecutive surveillance EGDs. A logistic regression model was built to determine whether persistence of NDBE independently protected against development of cancer. Of a total of 3515 patients with BE, 1401 patients met the inclusion criteria (93.3% white; 87.5% men; median age, 60 ±17 years). The median follow-up period was 5 ± 3.9 years (7846 patient-years). The annual risk of EAC in groups 1 to 5 was 0.32%, 0.27%, 0.16%, 0.2%, and 0.11%, respectively (P for trend = .03). After adjusting for age, sex, and length of BE, persistence of NDBE, based on multiple surveillance endoscopies, was associated with a gradually lower likelihood of progression to EAC. Persistence of NDBE over several endoscopic examinations identifies patients who are at low risk for development of EAC. These findings support lengthening surveillance intervals or discontinuing surveillance of patients with persistent NDBE. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PubMed

Radbruch, Alexander; Weberling, Lukas D; Kieslich, Pascal J; Hepp, Johanna; Kickingereder, Philipp; Wick, Wolfgang; Schlemmer, Heinz-Peter; Bendszus, Martin

2016-11-01

Recent studies reported an increase in the dentate nucleus (DN)-to-pons signal intensity (SI) ratio (DN-pons SI ratio) on unenhanced T1-weighted images in patients who received consecutive serial injections of linear gadolinium-based contrast agents (GBCAs). In contrast, most studies found no increase in the DN-pons SI ratio when patients were treated with consecutive serial injections of macrocyclic GBCAs. However, the potential difference between macrocyclic and linear GBCAs has never been assessed in individuals who received subsequent applications of both contrast agents. In this retrospective study, we assessed the evolution of the DN-pons SI ratio change in patients that were treated with a comparable number of serial consecutive injections of the linear GBCA gadopentetate dimeglumine and subsequent serial injections of the macrocyclic GBCAs gadobutrol and gadoterate meglumine. Data of 36 patients was analyzed. All patients underwent at least 5 consecutive administrations of the linear GBCA gadopentetate dimeglumine followed by an equal number of consecutive administrations of the macrocyclic GBCA gadobutrol. In 12 of the 36 patients, 5 or more final consecutive injections of the macrocyclic GBCA gadoterate meglumine were analyzed additionally. The difference of DN-pons SI ratios on unenhanced T1-weighted images was calculated by subtracting the ratio at the first examination from the ratio at the last examination in each of the 3 periods. The mean DN-pons SI ratio difference in the gadopentetate dimeglumine period was significantly greater than 0 (mean ± SD, 0.0448 ± 0.0345; P < 0.001), whereas the mean DN-pons SI ratio difference in the subsequent gadobutrol and gadoterate meglumine period was significantly smaller than 0 (gadobutrol: -0.0178 ± 0.0459, P = 0.026; gadoterate meglumine: -0.0250 ± 0.0284, P = 0.011). In this observational study, the application of the linear GBCA gadopentetate dimeglumine was associated with a DN-pons SI ratio increase, whereas subsequent applications of the macrocyclic GBCAs gadobutrol or gadoterate meglumine in the same patients were not. Rather, the current data tentatively suggest a decrease in preexisting hyperintensities over time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a washout effect or precipitation of gadolinium. Future patient studies need to include control groups to replicate the present results, and additional animal studies should be conducted to clarify the underlying mechanism of the proposed SI decrease.

A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies.

PubMed

Gleicher, N; Kim, A; Michaeli, T; Lee, H-J; Shohat-Tal, A; Lazzaroni, E; Barad, D H

2013-01-01

Is thin endometrium unresponsive to standard treatments expandable by intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF)? This cohort study is supportive of the effectiveness of G-CSF in expanding chronically unresponsive endometria. In a previous small case series, we reported the successful off-label use of G-CSF in four consecutive patients, who had previously failed to expand their endometria beyond 6.9 mm with the use of standard treatments. In a prospective observational cohort pilot study over 18 months, we described 21 consecutive infertile women with endometria <7 mm on the day of hCG administration in their first IVF cycles at our center. All previous cycles using traditional treatments with estradiol, sildenafil citrate (Viagra™) and/or beta-blockers had been unsuccessful. G-CSF (Nupogen™) was administered per intrauterine catheter by slow infusion before noon on the day of hCG administration. If the endometrium had not reached at least a 7-mm within 48h, a second infusion was given following oocyte retrieval. Primary and secondary main outcomes were an increase in endometrial thickness and clinical pregnancy, respectively. Endometrial thickness was assessed by vaginal ultrasound at the most expanded area of the endometrial stripe. This study was uncontrolled, each patient serving as her own control in a prospective evaluation of endometrial thickness. The mean ± SD age of the cohort was 40.5 ± 6.6 years, gravidity was 1.8 ± 2.1 (range 0-7) and parity was 0.4 ± 1.1 (range 0-4); 76.2% of women had, based on age-specific FSH and anti-Müllerian hormone, an objective diagnosis of diminished ovarian reserve and had failed 2.0 ± 2.1 prior IVF cycles elsewhere. With 5.2 ± 1.9 days between G-CSF perfusions and embryo transfers, endometrial thickness increased from 6.4 ± 1.4 to 9.3 ± 2.1 mm (P < 0.001). The Δ in change was 2.9 ± 2.0 mm, and did not vary between conception and non-conception cycles. A 19.1% ongoing clinical pregnancy rate was observed, excluding one ectopic pregnancy. Small sample size (but a highly selected patient population) in an uncontrolled cohort study and in unselected first IVF cycles at our center. This pilot study supports the utility of G-CSF in the treatment of chronically thin endometrium and suggests that such treatment will, in very adversely affected patients, result in low but very reasonable clinical pregnancy rates. This work was supported by the Foundation for Reproductive Medicine, New York, New York, USA, a not-for-profit research foundation and intramural grants from the Center for Human Reproduction (CHR)-New York. N.G. and D.H.B. are members of the board of the Foundation for Reproductive Medicine. N.G. is owner of CHR-New York, where the study was conducted. N.G. and D.H.B. have been recipients of research awards, travel grants and speaker honoraria from various pharmaceutical and medical device companies. None of these companies was, however, in any way associated with the materials and the manuscript presented here. N.G. and D.H.B. are listed as co-inventors on a number of awarded and still pending U.S. patents, none related to the materials presented here. N.G. is on the board of a medically related company, not in any way associated with the data presented here.

Use of healthcare, patient satisfaction and burden of care in Guillain-Barre syndrome.

PubMed

Forsberg, Anette; de Pedro-Cuesta, Jesús; Widén Holmqvist, Lotta

2006-07-01

The aim of this study was to investigate, in an unselected sample of patients with Guillain-Barré syndrome in Sweden, the utilization of healthcare resources, satisfaction with these resources, informal help and the burden of care on family caregivers during the first 2 years after onset. Forty-four patients were enrolled from 8 hospitals, and 42 of them were followed for 2 years. Data on the utilization of hospital inpatient and outpatient care, primary care and community-based services were collected via computerized registry information, medical records and a specific protocol. Patient satisfaction and the burden on family caregivers were studied using questionnaires. Forty-one patients required inpatient hospitalization for a mean of 82 days. Patients with persistent dependency during activities of daily living had significantly longer hospital stays and more days of outpatient rehabilitation. The majority of patients were satisfied with their care, but dissatisfaction was found regarding information and finances. At 2 years after onset, 26% of patients still depended on informal help. The spouses expressed increased concern and responsibility for household and family. Patients with persistent disability due to Guillain-Barré syndrome were found to have long-term need for services from the healthcare system and informal help.

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions.

PubMed

Stauder, Michael C; Macdonald, O Kenneth; Olivier, Kenneth R; Call, Jason A; Lafata, Kyle; Mayo, Charles S; Miller, Robert C; Brown, Paul D; Bauer, Heather J; Garces, Yolanda I

2011-05-01

Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Symptom severity scale of the DSM5 for schizophrenia, and other psychotic disorders: diagnostic validity and clinical feasibility.

PubMed

Ritsner, Michael S; Mar, Maria; Arbitman, Marina; Grinshpoon, Alexander

2013-06-30

Innovations in DSM5 include dimensional diagnosis of schizophrenia (SZ) and other psychotic (OP) disorders using the symptom severity scale (SS-DSM5). We evaluated the psychometric properties and diagnostic validity of the SS-DSM5 scale using a cross-sectional design and an unselected convenience unselected sample of 314 inpatients and outpatients with SZ/OP and mood disorders who received standard care in routine clinical practice. The SS-DSM5 scale, the Clinical Global Impression-Severity scale (CGI-S), the Positive and Negative Syndrome Scale (PANSS), and the Bech-Rafaelsen Mania Scale (BRMS) were administered. Factor structure, reliability, internal consistency, convergent and diagnostic ability of the DSM5-SS were evaluated. Factor analysis indicated two latent factors underlying the SS-DSM5 (Psychotic and Deficit sub-scales). Cronbach's alpha was >0.70. Convergent validity of the SS-DSM5 was highly significant. Patients with SZ/PO disorders were correctly diagnosed (77.9%) using the SS-DSM5 scale (72% using PANSS). The agreement of the diagnostic decisions between the SS-DSM5 and PANSS was substantial for SZ/PO disorders (Kappa=0.75). Classifying participants with SZ/PO versus mood disorders using SS-DSM5 provided a sensitivity of 95%, and specificity of 34%. Thus, this study suggests that the SS-DSM5 has acceptable psychometric properties and that its use in clinical practice and research is feasible in clinical settings. The dimensional option for the diagnosis of schizophrenia and related disorders using SS-DSM5 is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Introduction of an enhanced recovery protocol to reduce short-term complications following radical cystectomy and intestinal urinary diversion with vescica ileale Padovana neobladder.

PubMed

Cerruto, Maria Angela; De Marco, Vincenzo; D'Elia, Carolina; Bizzotto, Leonardo; Curti, Pierpaolo; Baldassarre, Roberto; Artibani, Walter

2014-01-01

To reduce short-term complications of radical cystectomy (RC) and intestinal urinary diversion with vescica ileale Padovana (VIP) neobladder, we described and assessed an enhanced recovery protocol (ERP) in a series of consecutive patients. An ERP was introduced focusing on reduced bowel preparation, standardized feeding and analgesic regimens. We analyzed the outcomes with all patients consecutively undergoing RC and VIP neobladder who met the following inclusion criteria: American Society of Anesthesiologists score <3; absence of malnutrition according to the Mini Nutritional Assessment-Short Form criteria; absence of inflammatory bowel diseases. Thirty-one consecutive patients were recruited to undergo our ERP. Mean age of patients was 62.16 years. No patients died due to surgical complications. Nine of 31 patients experienced complications (29.03%), none requiring surgical intervention. According to Clavien grading, all complications were grade <2. The application of our ERP to our patients undergoing RC and VIP neobladder contributed to reduce postoperative morbidity. Copyright © 2013 S. Karger AG, Basel.

The horizontal computerized rotational impulse test.

PubMed

Furman, Joseph M; Shirey, Ian; Roxberg, Jillyn; Kiderman, Alexander

2016-01-01

Whole-body impulsive rotations were used to overcome several limitations associated with manual head impulse testing. A computer-controlled rotational chair delivered brief, whole-body, earth-vertical axis yaw impulsive rotations while eye movements were measured using video-oculography. Results from an unselected group of 20 patients with dizziness and a group of 22 control subjects indicated that the horizontal computerized rotational head impulse test (crHIT) is well-tolerated and provides an estimate of unidirectional vestibulo-ocular reflex gain comparable to results from caloric testing. This study demonstrates that the horizontal crHIT is a new assessment tool that overcomes many of the limitations of manual head impulse testing and provides a reliable laboratory-based measure of unilateral horizontal semicircular canal function.

The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

PubMed

Gulevich, R G; Shikhevich, S G; Konoshenko, M Yu; Kozhemyakina, R V; Herbeck, Yu E; Prasolova, L A; Oskina, I N; Plyusnina, I Z

2015-05-15

The influence of social disturbance in early life on behavior, response of blood corticosterone level to restraint stress, and endocrine and morphometric indices of the testes was studied in 2-month Norway rat males from three populations: not selected for behavior (unselected), selected for against aggression to humans (tame), and selected for increased aggression to humans (aggressive). The experimental social disturbance included early weaning, daily replacement of cagemates from days 19 to 25, and subsequent housing in twos till the age of 2months. The social disturbance increased the latent period of aggressive behavior in the social interaction test in unselected males and reduced relative testis weights in comparison to the corresponding control groups. In addition, experimental unselected rats had smaller diameters of seminiferous tubules and lower blood testosterone levels. In the experimental group, tame rats had lower basal corticosterone levels, and aggressive animals had lower hormone levels after restraint stress in comparison to the control. The results suggest that the selection in two directions for attitude to humans modifies the response of male rats to social disturbance in early life. In this regard, the selected rat populations may be viewed as a model for investigation of (1) neuroendocrinal mechanisms responsible for the manifestation of aggression and (2) interaction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems in stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population

PubMed Central

Padula, Francesco; Cignini, Pietro; Giannarelli, Diana; Brizzi, Cristiana; Coco, Claudio; D’Emidio, Laura; Giorgio, Elsa; Giorlandino, Maurizio; Mangiafico, Lucia; Mastrandrea, Marialuisa; Milite, Vincenzo; Mobili, Luisa; Nanni, Cinzia; Raffio, Raffaella; Taramanni, Cinzia; Vigna, Roberto; Mesoraca, Alvaro; Bizzoco, Domenico; Gabrielli, Ivan; Di Giacomo, Gianluca; Barone, Maria Antonietta; Cima, Antonella; Giorlandino, Francesca Romana; Emili, Sabrina; Cupellaro, Marina; Giorlandino, Claudio

2014-01-01

Objectives to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. Methods a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11+0 and 13+6 weeks of gestation, between April 2007 and December 2008. Results of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2–100; false-positive rate (FPR) 4.7%, 95% CI 3.9–5.4; false-negative rate (FNR) 17.6%, 95% CI 0–35.8%]. Conclusion in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population. PMID:26266002

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants

PubMed Central

Buchanan, Adam H; Manickam, Kandamurugu; Meyer, Michelle N; Wagner, Jennifer K; Hallquist, Miranda L G; Williams, Janet L; Rahm, Alanna Kulchak; Williams, Marc S; Chen, Zong-Ming E; Shah, Chaitali K; Garg, Tullika K; Lazzeri, Amanda L; Schwartz, Marci L B; Lindbuchler, D'Andra M; Fan, Audrey L; Leeming, Rosemary; Servano, Pedro O; Smith, Ashlee L; Vogel, Victor G; Abul-Husn, Noura S; Dewey, Frederick E; Lebo, Matthew S; Mason-Suares, Heather M; Ritchie, Marylyn D; Davis, F Daniel; Carey, David J; Feinberg, David T; Faucett, W Andrew; Ledbetter, David H; Murray, Michael F

2018-01-01

Purpose The clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility. Methods Whole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient–participants and their clinicians. We queried patient–participants’ electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient–participants of eligible age who had begun risk management. Results Thirty-seven MyCode patient–participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer—including a stage 1C fallopian tube cancer—via these procedures. Conclusion Screening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility. PMID:29261187

Effect of Artificial Selection on Runs of Homozygosity in U.S. Holstein Cattle

PubMed Central

Kim, Eui-Soo; Cole, John B.; Huson, Heather; Wiggans, George R.; Van Tassell, Curtis P.; Crooker, Brian A.; Liu, George; Da, Yang; Sonstegard, Tad S.

2013-01-01

The intensive selection programs for milk made possible by mass artificial insemination increased the similarity among the genomes of North American (NA) Holsteins tremendously since the 1960s. This migration of elite alleles has caused certain regions of the genome to have runs of homozygosity (ROH) occasionally spanning millions of continuous base pairs at a specific locus. In this study, genome signatures of artificial selection in NA Holsteins born between 1953 and 2008 were identified by comparing changes in ROH between three distinct groups under different selective pressure for milk production. The ROH regions were also used to estimate the inbreeding coefficients. The comparisons of genomic autozygosity between groups selected or unselected since 1964 for milk production revealed significant differences with respect to overall ROH frequency and distribution. These results indicate selection has increased overall autozygosity across the genome, whereas the autozygosity in an unselected line has not changed significantly across most of the chromosomes. In addition, ROH distribution was more variable across the genomes of selected animals in comparison to a more even ROH distribution for unselected animals. Further analysis of genome-wide autozygosity changes and the association between traits and haplotypes identified more than 40 genomic regions under selection on several chromosomes (Chr) including Chr 2, 7, 16 and 20. Many of these selection signatures corresponded to quantitative trait loci for milk, fat, and protein yield previously found in contemporary Holsteins. PMID:24348915

Individual differences in circadian waveform of Siberian hamsters under multiple lighting conditions

PubMed Central

Evans, Jennifer A.; Elliott, Jeffrey A.; Gorman, Michael R.

2013-01-01

Because the circadian clock in the mammalian brain derives from a network of interacting cellular oscillators, characterizing the nature and bases of circadian coupling is fundamental to understanding how the pacemaker operates. Various phenomena involving plasticity in circadian waveform have been theorized to reflect changes in oscillator coupling; however, it remains unclear whether these different behavioral paradigms reference a unitary underlying process. To test if disparate coupling assays index a common mechanism, we examined whether there is co-variation among behavioral responses to various lighting conditions that produce changes in circadian waveform. Siberian hamsters, Phodopus sungorus, were transferred from long to short photoperiods to distinguish short photoperiod responders (SP-R) from non-responders (SP-NR). Short photoperiod chronotyped hamsters were subsequently transferred, along with unselected controls, to 24 h light:dark:light:dark cycles (LDLD) with dim nighttime illumination, a procedure that induces bifurcated entrainment. Under LDLD, SP-R hamsters were more likely to bifurcate their rhythms than SP-NR hamsters or unselected controls. After transfer from LDLD to constant dim light, SP-R hamsters were also more likely to become arrhythmic compared to SP-NR hamsters and unselected controls. In contrast, short photoperiod chronotype did not influence more transient changes in circadian waveform. The present data reveal a clear relationship in the plasticity of circadian waveform across three distinct lighting conditions, suggesting a common mechanism wherein individual differences reflect variation in circadian coupling. PMID:23010663

Humans identify negative (but not positive) arousal in silver fox vocalizations: implications for the adaptive value of interspecific eavesdropping.

PubMed

Filippi, Piera; Gogoleva, Svetlana S; Volodina, Elena V; Volodin, Ilya A; de Boer, Bart

2017-08-01

The ability to identify emotional arousal in heterospecific vocalizations may facilitate behaviors that increase survival opportunities. Crucially, this ability may orient inter-species interactions, particularly between humans and other species. Research shows that humans identify emotional arousal in vocalizations across multiple species, such as cats, dogs, and piglets. However, no previous study has addressed humans' ability to identify emotional arousal in silver foxes. Here, we adopted low- and high-arousal calls emitted by three strains of silver fox-Tame, Aggressive, and Unselected-in response to human approach. Tame and Aggressive foxes are genetically selected for friendly and attacking behaviors toward humans, respectively. Unselected foxes show aggressive and fearful behaviors toward humans. These three strains show similar levels of emotional arousal, but different levels of emotional valence in relation to humans. This emotional information is reflected in the acoustic features of the calls. Our data suggest that humans can identify high-arousal calls of Aggressive and Unselected foxes, but not of Tame foxes. Further analyses revealed that, although within each strain different acoustic parameters affect human accuracy in identifying high-arousal calls, spectral center of gravity, harmonic-to-noise ratio, and F0 best predict humans' ability to discriminate high-arousal calls across all strains. Furthermore, we identified in spectral center of gravity and F0 the best predictors for humans' absolute ratings of arousal in each call. Implications for research on the adaptive value of inter-specific eavesdropping are discussed.

Food wasting by house mice: variation among individuals, families, and genetic lines.

PubMed

Koteja, Paweł; Carter, Patrick A; Swallow, John G; Garland, Theodore

2003-11-01

Under ad libitum conditions, laboratory house mice (Mus domesticus) fragment considerable amounts of pelleted food and leave it scattered in their cages. The proportion of food thus wasted (in relation to food eaten) varies remarkably among individuals, from 2% to 40%, but is highly consistent in consecutive trials, even when the mice were moved from 22 to -10 degrees C and food consumption doubled. Food wasting did not differ either between the sexes or between genetic lines that had been selected (10 generations) for high voluntary wheel-running behavior (n=4) and their unselected control lines (n=4). However, it varied significantly among replicate lines within the selection groups and among families within the lines (coefficient of intraclass correlation for full sibs, rhof=0.41 in room temperature trials and rhof=0.34 in cold trials). Moreover, the percent of food wasted was negatively correlated with food consumption in the cold trials (males: r=-.36, females: r=-.20) and with total litter mass at weaning (the litters into which they were born; r=-.24), two traits that may affect Darwinian fitness. We conclude that food wastage should not be ignored without justification in calculations of food consumption. In addition, "table manners" can convey reliable information about family origin of an individual and its quality, and therefore could potentially play a role in establishment of social status.

Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies.

PubMed

Schwartz, Frederik; Bergmann, Natasha; Zerahn, Bo; Faber, Jens

2013-04-01

Painless thyroiditis (PT) is a transient kind of thyrotoxicosis, with lack of uptake on a thyroid scintigraphy in a non-tender thyroid gland, elevated anti-TPO antibodies, no fever, no history of increased iodine intake, and a normal sedimentation rate. The prevalence of PT varies hugely in the literature. To establish the incidence rate of PT in Denmark as well as to describe the phenotype of PT in more detail. Tc-99m pertechnetate scintigraphies were performed over a period of 9.75 years on 6022 consecutive patients (2349 had a thyrotoxic episode), and were divided into high or normal (5528), reduced (300) or lack of uptake (194). Patient records were evaluated: 292 with reduced, and 186 with lack of uptake. As a control measure, 230 consecutive thyrotoxic patients were also analyzed. Based on scintigraphies, 12 patients had PT, 10 with lack of uptake and two with reduced, corresponding to an incidence rate of 0.49/100,000 person years. It was predicted, that only one patient among the newly diagnosed consecutive thyrotoxic cohort had PT. This patient was identified. The prevalence of PT among thyrotoxic patients was 0.51% as evaluated by scintigraphy, and 0.43% among the biochemically thyrotoxic patient cohort. Twenty-five percent had more than one thyrotoxic episode, 75% had at least one subsequent hypothyroid episode, and 33% developed permanent hypothyroidism. PT presenting with symptomatic thyrotoxicosis is an extremely rare disease in Denmark. Symptomatic PT presents most often with no uptake on a Tc-99m pertechnetate scintigraphy. Clinical follow-up is essential.

Atherosclerotic renovascular disease – epidemiology, treatment and current challenges

PubMed Central

Vassallo, Diana

2017-01-01

The neutral results of recent large randomized controlled trials comparing renal revascularization with optimal medical therapy in patients with atherosclerotic renovascular disease (ARVD) have cast doubt on the role of revascularization in the management of unselected patients with this condition. However, these studies have strengthened the evidence base for the role of contemporary intensive medical vascular protection therapy and aggressive risk factor control in improving clinical outcomes in ARVD. Patients presenting with ‘high-risk’ clinical features such as uncontrolled hypertension, rapidly declining renal function or flash pulmonary oedema are underrepresented in these studies; hence these results may not be applicable to all patients with ARVD. In this ‘high-risk’ subgroup, conservative management may not be sufficient in preventing adverse events, and indeed, observational evidence suggests that this specific patient subgroup may gain benefit from timely renal revascularization. Current challenges include the development of novel diagnostic techniques to establish haemodynamic significance of a stenosis, patient risk stratification and prediction of post-revascularization outcomes to ultimately facilitate patient selection for revascularization. In this paper we describe the epidemiology of this condition and discuss treatment recommendations for this condition in light of the results of recent randomized controlled trials while highlighting important clinical unmet needs and challenges faced by clinicians managing this condition. PMID:29056991

The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase.

PubMed

Abbott, Lesleigh S; Deevska, Mariana; Fernandez, Conrad V; Dix, David; Price, Victoria E; Wang, Hao; Parker, Louise; Yhap, Margaret; Fitzgerald, Colleen; Barnard, Dorothy R; Berman, Jason N

2009-12-10

Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Children's Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.

Invasive strategy and frailty in very elderly patients with acute coronary syndromes.

PubMed

Llaó, Isaac; Ariza-Solé, Albert; Sanchis, Juan; Alegre, Oriol; López-Palop, Ramon; Formiga, Francesc; Marín, Francisco; Vidán, María T; Martínez-Sellés, Manuel; Sionis, Alessandro; Vives-Borrás, Miguel; Gómez-Hospital, Joan Antoni; Gómez-Lara, Josep; Roura, Gerard; Díez-Villanueva, Pablo; Núñez-Gil, Iván; Maristany, Jaume; Asmarats, Lluis; Bueno, Héctor; Abu-Assi, Emad; Cequier, Àngel

2018-04-03

Current guidelines recommend an early invasive strategy in patients with non-ST segment elevation acute coronary syndromes (NSTEACS). The role of an invasive strategy in frail elderly patients remains controversial. The LONGEVO-SCA registry included unselected NSTEACS patients aged ≥80 years. A geriatric assessment was performed during hospitalization, including frailty. We evaluated the impact of an invasive strategy during the admission on the incidence of cardiac death, reinfarction or new revascularisation at 6-months. From 531 patients included, 145 (27.3%) were frail. Mean age was 84.3 years. Most patients underwent an invasive strategy (407/531, 76.6%). Patients undergoing an invasive strategy were younger and had lower proportion of frailty (23.3% vs 40.3%, p<0.001). The incidence of cardiac events was more common in patients managed conservatively, after adjusting for confounding factors (sub-Hazard ratio (sHR) 2.32, 95% confidence interval (CI) 1.26-4.29, p=0.007). This association remained significant in non-frail patients (sHR 3.85, 95% CI 2.13-6.95, p=0.001), but was not significant in patients with established frailty criteria (sHR 1.40, 95% CI 0.72-2.75, p=0.325). The interaction invasive strategy-frailty was significant (p=0.032) Conclusions: An invasive strategy was independently associated with better outcomes in very elderly patients with NSTEACS. This association was different according to frailty status.

Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PubMed

Helbig, Katherine L; Farwell Hagman, Kelly D; Shinde, Deepali N; Mroske, Cameron; Powis, Zöe; Li, Shuwei; Tang, Sha; Helbig, Ingo

2016-09-01

To assess the yield of diagnostic exome sequencing (DES) and to characterize the molecular findings in characterized and novel disease genes in patients with epilepsy. In an unselected sample of 1,131 patients referred for DES, overall results were compared between patients with and without epilepsy. DES results were examined based on age of onset and epilepsy diagnosis. Positive/likely positive results were identified in 112/293 (38.2%) epilepsy patients compared with 210/732 (28.7%) patients without epilepsy (P = 0.004). The diagnostic yield in characterized disease genes among patients with epilepsy was 33.4% (105/314). KCNQ2, MECP2, FOXG1, IQSEC2, KMT2A, and STXBP1 were most commonly affected by de novo alterations. Patients with epileptic encephalopathies had the highest rate of positive findings (43.4%). A likely positive novel genetic etiology was proposed in 14/200 (7%) patients with epilepsy; this frequency was highest in patients with epileptic encephalopathies (17%). Three genes (COQ4, DNM1, and PURA) were initially reported as likely positive novel disease genes and were subsequently corroborated in independent peer-reviewed publications. DES with analysis and interpretation of both characterized and novel genetic etiologies is a useful diagnostic tool in epilepsy, particularly in severe early-onset epilepsy. The reporting on novel genetic etiologies may further increase the diagnostic yield.Genet Med 18 9, 898-905.

Brain Gut Microbiome Interactions and Functional Bowel Disorders

PubMed Central

Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

2014-01-01

Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

Detecting re-infection in patients after an initial diagnosis of gonorrhoea: is routine recall for re-screening useful?

PubMed

Fernando, K A; Fowler, T; Harding, J; Flew, S; Caley, M; Phattey, J; Ross, Jdc

2015-08-01

To assess the outcome of routine sexually transmitted infection re-screening after a three-month interval in unselected patients diagnosed with gonorrhoea, we sought to assess whether this active approach would result in an increase in the number of people attending clinic and subsequently diagnosed with gonorrhoea re-infection, compared with normal re-presentation rates. A recall group of patients were invited for re-screening three months after their initial diagnosis of gonorrhoea. Permission was sought to send a reminder two weeks prior to their scheduled recall appointment. Comparisons were made with a historical control group of patients with gonorrhoea in the absence of any formal recall. Of the 242 patients in the intervention arm, 96 (40%) re-attended within six months, and 15 (6%) tested gonorrhoea positive. Two hundred and two patients were assessed in the control group, of whom 45 (22%) re-attended within six months, and 13 (6%) tested gonorrhoea positive. Women were more likely than men to re-attend following active recall, but they were not at higher risk of re-attending while re-infected with gonorrhoea. Active recall following a gonorrhoea diagnosis significantly increases re-attendance rates for repeat screening but did not result in an increased number of subsequent gonorrhoea diagnoses. © The Author(s) 2014.

DIAGNOSIS OF ENDOCRINE DISEASE: Prevalence of hypercortisolism in type 2 diabetes patients: a systematic review and meta-analysis.

PubMed

Steffensen, Charlotte; Pereira, Alberto M; Dekkers, Olaf M; Jørgensen, Jens Otto L

2016-12-01

Type 2 diabetes (T2D) and Cushing's syndrome (CS) share clinical characteristics, and several small studies have recorded a high prevalence of hypercortisolism in T2D, which could have therapeutic implications. We aimed to assess the prevalence of endogenous hypercortisolism in T2D patients. Systematic review and meta-analysis of the literature. A search was performed in SCOPUS, MEDLINE, and EMBASE for original articles assessing the prevalence of endogenous hypercortisolism and CS in T2D. Data were pooled in a random-effect logistic regression model and reported with 95% confidence intervals (95% CI). Fourteen articles were included, with a total of 2827 T2D patients. The pooled prevalence of hypercortisolism and CS was 3.4% (95% CI: 1.5-5.9) and 1.4% (95 CI: 0.4-2.9) respectively. The prevalence did not differ between studies of unselected patients and patients selected based on the presence of metabolic features such as obesity or poor glycemic control (P = 0.41 from meta-regression). Imaging in patients with hypercortisolism (n = 102) revealed adrenal tumors and pituitary tumors in 52 and 14% respectively. Endogenous hypercortisolism is a relatively frequent finding in T2D, which may have therapeutic implications. © 2016 European Society of Endocrinology.

Spatial working memory function in twins with schizophrenia and bipolar disorder.

PubMed

Pirkola, Tiia; Tuulio-Henriksson, Annamari; Glahn, David; Kieseppä, Tuula; Haukka, Jari; Kaprio, Jaakko; Lönnqvist, Jouko; Cannon, Tyrone D

2005-12-15

Family studies are in conflict as to whether schizophrenia and bipolar disorder have independent genetic etiologies. Given the relatively low prevalence (approximately 1%) of these disorders, the use of quantitative endophenotypic markers of genetic liability might provide a more sensitive strategy for evaluating their genetic overlap. We have previously demonstrated that spatial working memory deficits increase in a dose-dependent fashion with increasing genetic proximity to a proband among the unaffected co-twins of schizophrenic patients. Here, we evaluated whether such deficits might also mark genetic susceptibility to bipolar disorder. The Wechsler Memory Scale-Revised Visual Memory Span and Digit Span subtests were administered to 46 schizophrenic patients, 32 of their unaffected co-twins, 22 bipolar patients, 16 of their unaffected co-twins, and 100 control twins, representing unselectively nationwide twin samples. Schizophrenic patients and their unaffected co-twins performed significantly worse than control subjects on the spatial working memory task, whereas only the schizophrenic patients performed significantly below the control subjects on the verbal working memory task. Neither bipolar patients nor their unaffected co-twins differed from control subjects on these measures. Our findings support the hypothesis that impairment in spatial working memory might effectively reflect an expression of genetic liability to schizophrenia but less clearly to bipolar disorder.

Five year follow-up after autologous peripheral blood hematopoietic stem cell transplantation for refractory, chronic, corticosteroid-dependent systemic lupus erythematosus: effect of conditioning regimen on outcome.

PubMed

Burt, Richard K; Han, Xiaoqiang; Gozdziak, Paula; Yaung, Kim; Morgan, Amy; Clendenan, Allison M; Henry, Jacquelyn; Calvario, Michelle A; Datta, Syamal K; Helenowski, Irene; Schroeder, James

2018-05-31

Some patients with systemic lupus erythematosus (SLE) are refractory to traditional therapies, dependent on chronic corticosteroids, have organ damage, and are at high risk of mortality. In this group of patients, we report outcome at a median of five years after autologous hematopoietic stem cell transplant (HSCT) using two different non-myeloablative regimens. Four patients received a conditioning regimen of cyclophosphamide (200 mg/kg) and alemtuzumab (60 mg), while 26 patients underwent conditioning with cyclophosphamide (200 mg/kg), rATG (Thymoglobulin) (5.5 mg/kg), and rituximab 1000 mg. Unselected peripheral blood stem cells were infused on day 0. There were no treatment related deaths. Of the four patients treated with cyclophosphamide and alemtuzumab, none entered remission. For the 26 patients treated with cyclophosphamide, rATG, and rituximab, disease remission defined as no immune suppressive drugs except hydroxychloroquine and/or 10 mg or less of prednisone a day was 92% at 6 months, 92% at one year, 81% at 2 years, 71% at 3 years, and 62% at 4 and 5 years post-HSCT. Autologous HSCT outcome is dependent on the conditioning regimen but prior organ damage may cause lingering symptoms.

Bile acid malabsorption: an under-investigated differential diagnosis in patients presenting with diarrhea predominant irritable bowel syndrome type symptoms.

PubMed

Kurien, Matthew; Evans, Kate E; Leeds, John S; Hopper, Andy D; Harris, Andrew; Sanders, David S

2011-07-01

Bile acid malabsorption (BAM) has been reported as a possible cause of diarrhea predominant irritable bowel syndrome (D-IBS) type symptoms. We aimed to determine how commonly patients with D-IBS type symptoms had a diagnosis of BAM as demonstrated by a positive SeHCAT (75 Selenium-homocholic acid taurine) test (retention <10% at seven days). A retrospective analysis was undertaken of patient's records for all patients who underwent a SeHCAT test between 2001 and 2009 in a tertiary hospital (Group A). Concurrently, a cohort of patients with Rome II D-IBS type symptoms was examined to determine the potential utility of SeHCAT test (Group B). In Group A 39.2% (n = 107/273) of patients had a positive SeHCAT result. The median time from first hospital visit to SeHCAT result was 30 weeks. Predictive factors for BAM: terminal ileal Crohn's disease (p < 0.01), terminal ileal resection (p < 0.01), and previous cholecystectomy (p < 0.01). 33.6% of patients who had a positive SeHCAT also had Rome II D-IBS. In Group B the D-IBS control cohort only 1.9% of patients had undergone a SeHCAT scan (p < 0.001 compared to Group A). BAM is common and should be considered earlier when investigating unselected patients with D-IBS type symptoms.

Inadequate Diagnostic Evaluation in Young Patients Registered with a Diagnosis of Dementia: A Nationwide Register-Based Study

PubMed Central

Salem, Lise Cronberg; Andersen, Birgitte Bo; Nielsen, T. Rune; Stokholm, Jette; Jørgensen, Martin Balslev; Waldemar, Gunhild

2014-01-01

Background Establishing a diagnosis of dementia in young patients may be complex and have significant implications for the patient. The aim of this study was to evaluate the quality of the diagnostic work-up in young patients diagnosed with dementia in the clinical routine. Methods Two hundred patients were randomly selected from 891 patients aged ≤65 years registered with a diagnosis of dementia for the first time in 2008 in Danish hospitals, and 159 medical records were available for review. Three raters evaluated their medical records for the completeness of the diagnostic work-up on which the diagnosis of dementia had been based, using evidence-based guidelines for the diagnostic evaluation of dementia as reference standards. Results According to the rater review, only 111 (70%) patients met the clinical criteria for dementia. An acceptable diagnostic work-up including all items of recommended basic diagnostic evaluation was performed in only 24%, although more often (28%) in the subgroup of patients where dementia was confirmed by raters. Conclusion This first nationwide study of unselected young patients registered with a diagnosis of dementia indicated that the concept of dementia may be misinterpreted by clinicians and that a diagnosis of dementia in the young is only rarely based on a complete basic diagnostic work-up, calling for increased competency. PMID:24711812

Risk of ischemic stroke after an acute myocardial infarction in patients with diabetes mellitus.

PubMed

Jakobsson, Stina; Bergström, Lisa; Björklund, Fredrik; Jernberg, Tomas; Söderström, Lars; Mooe, Thomas

2014-01-01

Incidence, any trend over time, and predictors of ischemic stroke after an acute myocardial infarction (AMI) in diabetic patients are unknown. Data for 173,233 unselected patients with an AMI, including 33,503 patients with diabetes mellitus, were taken from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) during 1998 to 2008. Ischemic stroke events were recorded during 1 year of follow-up. Patients with diabetes mellitus more often had a history of cardiovascular disease, received less reperfusion therapy, and were treated with acetylsalicylic acid, P2Y12 inhibitors, and statins to a lesser extent compared with patients without diabetes mellitus. However, the use of evidence-based therapies increased markedly in both groups during the study period. The incidence of ischemic stroke during the first year after AMI decreased from 7.1% to 4.7% in patients with diabetes mellitus and from 4.2% to 3.7% in patients without diabetes mellitus. Risk reduction was significantly larger in the diabetic subgroup. Reperfusion therapy, acetylsalicylic acid, P2Y12 inhibitors, and statins were independently associated with the reduced stroke risk. Ischemic stroke is a fairly common complication after an AMI in patients with diabetes mellitus, but the risk of stroke has decreased during recent years. The increased use of evidence-based therapies contributes importantly to this risk reduction, but there is still room for improvement.

The effect of queen pheromone status on Varroa mite removal from honey bee colonies with different grooming ability.

PubMed

Bahreini, Rassol; Currie, Robert W

2015-07-01

The objective of this study was to assess the effects of honey bees (Apis mellifera L.) with different grooming ability and queen pheromone status on mortality rates of Varroa mites (Varroa destructor Anderson and Trueman), mite damage, and mortality rates of honey bees. Twenty-four small queenless colonies containing either stock selected for high rates of mite removal (n = 12) or unselected stock (n = 12) were maintained under constant darkness at 5 °C. Colonies were randomly assigned to be treated with one of three queen pheromone status treatments: (1) caged, mated queen, (2) a synthetic queen mandibular pheromone lure (QMP), or (3) queenless with no queen substitute. The results showed overall mite mortality rate was greater in stock selected for grooming than in unselected stock. There was a short term transitory increase in bee mortality rates in selected stock when compared to unselected stock. The presence of queen pheromone from either caged, mated queens or QMP enhanced mite removal from clusters of bees relative to queenless colonies over short periods of time and increased the variation in mite mortality over time relative to colonies without queen pheromone, but did not affect the proportion of damaged mites. The effects of source of bees on mite damage varied with time but damage to mites was not reliably related to mite mortality. In conclusion, this study showed differential mite removal of different stocks was possible under low temperature. Queen status should be considered when designing experiments using bioassays for grooming response.

Patterns of disease control and survival in patients with melanoma brain metastases undergoing immune-checkpoint blockade.

PubMed

Milsch, Laura; Gesierich, Anja; Kreft, Sophia; Livingstone, Elisabeth; Zimmer, Lisa; Goebeler, Matthias; Schadendorf, Dirk; Schilling, Bastian

2018-06-12

Immune-checkpoint blockers (ICBs) significantly prolong overall survival (OS) in patients with advanced melanoma. Limited data are available on the efficacy and clinical benefit in patients with melanoma brain metastases (MBMs). The aim of this study was to determine whether ICB is active in an unselected cohort treated of patients with known brain metastases and if disease control correlates with the survival. A total of 385 patients with metastatic malignant melanoma treated with ICB as monotherapy between 2005 and 2017 in two tertiary referral centres were included. Patient records were searched for the development of brain metastases. Demographic and clinical data of all patients were collected retrospectively. We identified 177 patients with MBM who received ICBs (ipilimumab, nivolumab, pembrolizumab). Patients with and without brain metastases received similar ICB regimens. Prognosis was inferior in patients with brain metastases; patients with >1 brain metastasis showed even poorer survival. For extracranial (ec) metastases, disease control was associated with improved survival. However, when comparing patients with intracranial (ic) disease control during immunotherapy to patients with ic disease progression, no difference in OS could be observed. In our study, ec disease control was the dominant predictive factor for OS in both patients with or without melanoma brain metastases. These data indicate that clinical trials in melanoma patients with brain metastases should address end-points such as symptom control, quality of life or OS in addition to ic response rates. Copyright © 2018 Elsevier Ltd. All rights reserved.

An inherited NBN mutation is associated with poor prognosis prostate cancer

PubMed Central

Cybulski, C; Wokołorczyk, D; Kluźniak, W; Jakubowska, A; Górski, B; Gronwald, J; Huzarski, T; Kashyap, A; Byrski, T; Dębniak, T; Gołąb, A; Gliniewicz, B; Sikorski, A; Świtała, J; Borkowski, T; Borkowski, A; Antczak, A; Wojnar, Ł; Przybyła, J; Sosnowski, M; Małkiewicz, B; Zdrojowy, R; Sikorska-Radek, P; Matych, J; Wilkosz, J; Różański, W; Kiś, J; Bar, K; Bryniarski, P; Paradysz, A; Jersak, K; Niemirowicz, J; Słupski, P; Jarzemski, P; Skrzypczyk, M; Dobruch, J; Domagała, P; Narod, S A; Lubiński, J

2013-01-01

Background: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. Methods: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). Results: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ⩽60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. Conclusion: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment. PMID:23149842

Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.

PubMed

Tutt, Andrew; Tovey, Holly; Cheang, Maggie Chon U; Kernaghan, Sarah; Kilburn, Lucy; Gazinska, Patrycja; Owen, Julie; Abraham, Jacinta; Barrett, Sophie; Barrett-Lee, Peter; Brown, Robert; Chan, Stephen; Dowsett, Mitchell; Flanagan, James M; Fox, Lisa; Grigoriadis, Anita; Gutin, Alexander; Harper-Wynne, Catherine; Hatton, Matthew Q; Hoadley, Katherine A; Parikh, Jyoti; Parker, Peter; Perou, Charles M; Roylance, Rebecca; Shah, Vandna; Shaw, Adam; Smith, Ian E; Timms, Kirsten M; Wardley, Andrew M; Wilson, Gregory; Gillett, Cheryl; Lanchbury, Jerry S; Ashworth, Alan; Rahman, Nazneen; Harries, Mark; Ellis, Paul; Pinder, Sarah E; Bliss, Judith M

2018-05-01

Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum. We assessed the efficacy of carboplatin and another mechanistically distinct therapy, docetaxel, in a phase 3 trial in subjects with unselected advanced TNBC. A prespecified protocol enabled biomarker-treatment interaction analyses in gBRCA-BC and BRCAness subgroups. The primary endpoint was objective response rate (ORR). In the unselected population (376 subjects; 188 carboplatin, 188 docetaxel), carboplatin was not more active than docetaxel (ORR, 31.4% versus 34.0%, respectively; P = 0.66). In contrast, in subjects with gBRCA-BC, carboplatin had double the ORR of docetaxel (68% versus 33%, respectively; biomarker, treatment interaction P = 0.01). Such benefit was not observed for subjects with BRCA1 methylation, BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay. Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup. We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations, but not BRCA1 methylation or Myriad HRD analyses, to inform choices on platinum-based chemotherapy. Additionally, gene expression analysis of basal-like cancers may also influence treatment selection.

Prevalence of illicit drug use in pregnant women in a Wisconsin private practice setting.

PubMed

Schauberger, Charles W; Newbury, Emily J; Colburn, Jean M; Al-Hamadani, Mohammed

2014-09-01

We sought to measure the prevalence of illicit drug use in our obstetric population, to identify the drugs being used, and to determine whether a modified version of the 4Ps Plus screening tool could serve as an initial screen. In this prospective study, urine samples of 200 unselected patients presenting for initiation of prenatal care in a Wisconsin private practice were analyzed for evidence of the use of illicit drugs. Of 200 patients, 26 (13%) had evidence of drugs of abuse in their urine samples. Marijuana (7%) and opioids (6.5%) were the most commonly identified drugs. Adding 5 questions about drug or alcohol use to the obstetric intake questionnaire proved sensitive in identifying patients with high risks of having a positive drug screen. The rate of drug use in our low-risk population was higher than expected and may reflect increasing rates of drug use across the United States. Enhanced screening should be performed to identify patients using illicit drugs in pregnancy to improve their care. Medical centers and communities may benefit from periodic testing of their community prevalence rates to aid in appropriate care planning. Copyright © 2014 Mosby, Inc. All rights reserved.

Genomic Alterations in Advanced Esophageal Cancer May Lead to Subtype-Specific Therapies

PubMed Central

Forde, Patrick M.

2013-01-01

The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8–12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease. PMID:23853247

Common medium versus advanced IVF medium for cryopreserved oocytes in heterologous cycles.

PubMed

Poverini, R; Lisi, R; Lisi, F; Berlinghieri, V; Bielli, W; Carfagna, P; Costantino, A; Iacomino, D; Nicodemo, G

2018-12-01

Granulocyte-macrophage colony-stimulation factor plays different crucial roles during embryo implantation and subsequent development. Here we aimed to evaluate the effects of embryo cell culture medium, with the inclusion of granulocyte-macrophage colony-stimulation factor (GM-CSF), on embryo development and pregnancy rate. To this end, we took advantage of our retrospective observational study to correlate the outcomes from two different culture media. We included in this study 25 unselected patient from our IVF Center that underwent heterologous IVF cycle with crypreserved oocytes. We analyze the fertilization rate, pregnancy rate, and embryo quality at different day of transfer obtained from two different media composition. Our results show that the rate of fertilization and the pregnancy rate were increased using medium added with this particular type of cytokines (GM-CSF).

Somatic mutations in the transcriptional corepressor gene BCORL1 in adult acute myelogenous leukemia

PubMed Central

Li, Meng; Collins, Roxane; Jiao, Yuchen; Ouillette, Peter; Bixby, Dale; Erba, Harry; Vogelstein, Bert; Kinzler, Kenneth W.

2011-01-01

To further our understanding of the genetic basis of acute myelogenous leukemia (AML), we determined the coding exon sequences of ∼ 18 000 protein-encoding genes in 8 patients with secondary AML. Here we report the discovery of novel somatic mutations in the transcriptional corepressor gene BCORL1 that is located on the X-chromosome. Analysis of BCORL1 in an unselected cohort of 173 AML patients identified a total of 10 mutated cases (6%) with BCORL1 mutations, whereas analysis of 19 AML cell lines uncovered 4 (21%) BCORL1 mutated cell lines. The majority (87%) of the mutations in BCORL1 were predicted to inactivate the gene product as a result of nonsense mutations, splice site mutation, or out-of-frame insertions or deletions. These results indicate that BCORL1 by genetic criteria is a novel candidate tumor suppressor gene, joining the growing list of genes recurrently mutated in AML. PMID:21989985

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

NASA Technical Reports Server (NTRS)

Wu, C. L.; Denq, J. C.; Harper, C. M.; O'Brien, P. C.; Low, P. A.

1998-01-01

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

Evidence of SV40 infections in hospitalized children

NASA Technical Reports Server (NTRS)

Butel, J. S.; Jafar, S.; Wong, C.; Arrington, A. S.; Opekun, A. R.; Finegold, M. J.; Adam, E.

1999-01-01

Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.

[Single embryo transfer: is Scandinavian model valuable in France?].

PubMed

Belaisch-Allart, J; Mayenga, J-M; Grefenstette, I; Chouraqui, A; Serkine, A-M; Abirached, F; Kulski, O

2008-11-01

The aim of infertility treatment is clearly to obtain one healthy baby. If the transfer of a top quality single embryo could provide a baby to all the patients, there would be no more discussion. The problem is that, nowadays, French pregnancy rates after fresh embryo or frozen embryo transfer are not the same as in Nordic countries. All studies show that in unselected patients, single embryo transfer decreases twin pregnancy rate but decreases pregnancy rate too. Pregnancy rate is dependent on embryo quality, women's age, rank of IVF attempt (clear data) but also on body mass index, ovarian reserve, smoking habits. All these data cannot be taken into account in a law. That is the reason why a flexible policy of transfer adapted to each couple is preferable. Each couple and each IVF team are unique and must keep the freedom to choose how many embryos must be transferred to obtain healthy babies, and to avoid twin pregnancies but without demonizing them.

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

Ausborn, Natalie L.; Le, Quynh Thu; Bradley, Jeffrey D.

Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growthmore » factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.« less

Comparison of 2-dimensional, 3-dimensional, and vascular ultrasonographic parameters for endometrial receptivity between 2 consecutive stimulated in vitro fertilization cycles.

PubMed

Ng, Ernest Hung Yu; Chan, Carina Chi Wai; Tang, Oi Shan; Ho, Pak Chung

2007-07-01

We compared the ultrasonographic parameters for endometrial receptivity between 2 consecutive in vitro fertilization (IVF) cycles in the same patients. Patients who had undergone 2 in vitro fertilization cycles between November 2002 and December 2004 were recruited. A 3-dimensional ultrasonographic examination with power Doppler imaging was performed on the day of oocyte retrieval to determine the endometrial thickness, endometrial pattern, pulsatility and resistive indices of uterine vessels, endometrial volume, vascularization index, flow index, and vascularization flow index of endometrial and subendometrial regions. Of 662 patients, 95 (14.4%) underwent 2 consecutive cycles using the same stimulation regimen during the study period. There were no significant differences in these ultrasonographic parameters between the first and second cycles. The intraclass correlation coefficient (ICC) for endometrial volume was significantly higher than that of other ultrasonographic parameters. The ICC for the endometrial thickness, uterine pulsatility index, and endometrial 3-dimensional power Doppler flow indices were similar. Ultrasonographic parameters for endometrial receptivity were comparable in the 2 consecutive stimulated cycles. The endometrial volume had the highest ICC among these ultrasonographic parameters and was most reproducible between 2 cycles.

Prospective study of lidocaine, bupivacaine, and epinephrine levels and blood loss in patients undergoing liposuction and abdominoplasty.

PubMed

Swanson, Eric

2012-09-01

Bupivacaine levels have not been measured in cosmetic surgery patients to establish safety. Blood loss has been underestimated using the small volumes present in the aspirate. The proportion of wetting solution removed by liposuction has not been reliably ascertained. To remedy these deficiencies, a prospective study was undertaken among 322 consecutive patients presenting for superwet ultrasonic liposuction and/or abdominoplasty, and other combined procedures, using infusions containing 0.05% lidocaine (liposuction) and/or 0.025% bupivacaine (abdominoplasty) with 1:500,000 epinephrine. Plasma levels of lidocaine, bupivacaine, and epinephrine were studied in a subset of 76 consecutive patients, including hourly intraoperative samples in 39 consecutive patients. Anesthetic levels were also measured in 12 consecutive patients during the 24-hour period after infusion. The maximum lidocaine dose was 3243 mg and the maximum level was 2.10 μg/ml. The maximum bupivacaine dose was 550 mg and the maximum level was 0.81 μg/ml. No clinical toxicity was encountered. Estimated blood loss from liposuction was 217.5 cc + 187 cc/liter of aspirate (r = 0.65). Abdominoplasty added 290 cc of blood loss, on average. The mean proportion of wetting solution removed by liposuction was 9.8 percent. Bupivacaine may be safely used in cosmetic surgery. A concentration of 1:500,000 epinephrine is safe and effective when administered as part of a wetting solution that is limited to less than 5 liters. Estimated blood loss is higher than previous estimates based on lipocrits. Combination procedures are safe.

Surgery in Jehovah's Witnesses – our experience

PubMed Central

Kujawski, Ryszard; Mik, Michał; Berut, Maciej; Dziki, Łukasz; Dziki, Adam

2015-01-01

Introduction Surgeons face a special challenge in treating Jehovah's Witnesses who refuse blood transfusion. Aim To present our surgical experience with this group of patients operated on in our department. Material and methods A retrospective study of 16 unselected Jehovah's Witnesses patients was conducted between October 2004 and February 2012. We analysed gender, age, haemogram before and after surgery, types of surgery, postoperative complications and the need for blood transfusion, and/or other drugs stimulating erythrogenesis. Results Eighty-one percent of patients were women; the average age of all patients was 57.3 years. Mean haemoglobin level, preoperative, postoperative, and on the day of discharge from hospital, was 12.5 g/dl, 9.7 g/dl, and 9.29 g/dl, respectively. Over the same time period, mean red blood cell count was 4.53 mln/µl, 3.58 mln/µl, and 3.37 mln/µl, respectively. Two out of 16 patients agreed to have blood transfusion. Drugs used for erythropoiesis stimulation included rEPO, ferrum, and folic acid. No surgical death was noted. Conclusions We found that abdominal surgery was safe in our small group of Jehovah's Witness patients. However, all Jehovah's Witness patients should be fully informed about the type of procedure and possible consequences of blood transfusion refusal. Two of our patients agreed to blood transfusion in the face of risk of death. PMID:25960813

Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation.

PubMed

Rostagno, Carlo; Olivo, Giuseppe; Comeglio, Marco; Boddi, Vieri; Banchelli, Michela; Galanti, Giorgio; Gensini, Gian Franco

2003-06-01

The study was designed to evaluate the prognostic value of the 6-min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF). Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event-free survival (death, heart transplantation). Sixty-six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300-450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox-stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers. A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.

Impairments in proverb interpretation following focal frontal lobe lesions☆

PubMed Central

Murphy, Patrick; Shallice, Tim; Robinson, Gail; MacPherson, Sarah E.; Turner, Martha; Woollett, Katherine; Bozzali, Marco; Cipolotti, Lisa

2013-01-01

The proverb interpretation task (PIT) is often used in clinical settings to evaluate frontal “executive” dysfunction. However, only a relatively small number of studies have investigated the relationship between frontal lobe lesions and performance on the PIT. We compared 52 patients with unselected focal frontal lobe lesions with 52 closely matched healthy controls on a proverb interpretation task. Participants also completed a battery of neuropsychological tests, including a fluid intelligence task (Raven’s Advanced Progressive Matrices). Lesions were firstly analysed according to a standard left/right sub-division. Secondly, a finer-grained analysis compared the performance of patients with medial, left lateral and right lateral lesions with healthy controls. Thirdly, a contrast of specific frontal subgroups compared the performance of patients with medial lesions with patients with lateral frontal lesions. The results showed that patients with left frontal lesions were significantly impaired on the PIT, while in patients with right frontal lesions the impairments approached significance. Medial frontal patients were the only frontal subgroup impaired on the PIT, relative to healthy controls and lateral frontal patients. Interestingly, an error analysis indicated that a significantly higher number of concrete responses were found in the left lateral subgroup compared to healthy controls. We found no correlation between scores on the PIT and on the fluid intelligence task. Overall our results suggest that specific regions of the frontal lobes contribute to the performance on the PIT. PMID:23850600

Do attendees at sexual health and HIV clinics prefer to be called in by name or number?

PubMed

Dabis, R; Nightingale, P; Kumar, V; Jaffer, K; Radcliffe, K

2014-06-01

Calling patients in from the waiting area is an important aspect of the initial medical encounter. According to national and international guidelines, clinics should decide on an appropriate way of calling patients in from the waiting room for consultations; however, no preference is actually recommended. A survey was carried out to see if patients were happy to be called in by number, first name, surname, full name, or title (Mr/Mrs/Miss/Ms) followed by surname. One hundred unselected patients were drawn from each clinic including; a genito-urinary medicine (GUM), a co-located GUM (cGUM) and co-located reproductive health (cRH), an HIV and a reproductive health (RH) clinic. Patients from the GUM, cGUM, cRH and RH clinics preferred to be called in by number rather than full name or title. Patients from the cRH clinic also preferred number to first name. In contrast, patients from the HIV clinics preferred to be called in by first name rather than number, surname, full name or title. Following this survey it would appear that number would be the most popular method of calling patients in sexual and reproductive health clinics and first name is the choice in HIV clinics. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Short-term improvement of erectile dysfunction by viewing humorous films in patients with atopic dermatitis.

PubMed

Kimata, Hajime

2008-09-01

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by eczema, pruritus and cutaneous hyperreactivity to allergic triggers. We and others have reported that psychogenic stress aggravates these symptoms, while viewing humorous films alleviates them. We have also found that many AD patients suffer from erectile dysfunction (ED). ED exhibits multifactorial etiologies, including psychogenic stress and reduction of serum testosterone levels. This study assessed the effects of viewing humorous films on ED in patients with AD. The effects of viewing humorous films on International Index Erectile Function (IIEF) domain (erectile function, orgasmic function, sexual desire, intercourse satisfaction, overall satisfaction) were studied. Subjects comprised 36 AD patients with ED and their healthy wives. Randomly assigned 18 patients and their healthy wives first viewed humorous films on three consecutive days (Days 1-3). After 2 weeks, they viewed control nonhumorous weather information films on three consecutive days (Days 1-3). Alternatively, other 18 patients and their wives first viewed control films on three consecutive days, and after 2 weeks they viewed humorous films on three consecutive days. Severity of ED and serum testosterone and estradiol levels were assessed 1 day before viewing (Day -1) and 1-4 days after viewing (Days 4-7). Viewing humorous films significantly improved the IIEF domain in association with increased serum testosterone levels and decreased serum estradiol levels on Day 4, while viewing control films failed to do so. However, this effect was short-term. After 4 days of viewing (Day 7), no improvement in ED or modulation of serum sex hormone levels was observed. Viewing humorous films improved ED in AD patients in association with increased serum testosterone levels and decreased serum estradiol levels. These results may be useful for the study and treatment of ED.

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study

PubMed Central

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-01-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. PMID:25533447

Is near infrared fluorescence imaging using indocyanine green dye useful in robotic partial nephrectomy: a prospective comparative study of 94 patients.

PubMed

Krane, L Spencer; Manny, Theodore B; Hemal, Ashok K

2012-07-01

To compare a consecutive prospective cohort of patients who underwent robotic partial nephrectomy (RPN) with near infrared fluorescence (NIRF) imaging with indocyanine green dye (ICG) with a previous consecutive patient cohort. A total of 47 consecutive patients with renal masses suspicious for malignancy undergoing RPN were given 5-7.5 mg of ICG before hilar clamping or tumor excision. This cohort of patients was compared with 47 immediate previous consecutive patients who had undergone RPN without NIRF real-time imaging using ICG. The intraoperative, perioperative, and postoperative parameters were collected in an institutional review board-approved prospective database. The preoperative demographics and tumor complexity according to the nephrometry or preoperative aspects and dimensions used for an anatomic (PADUA) scores were similar. The mean warm ischemia time was significantly decreased in the ICG group (15 vs 17 minutes, P = .01). The median hospital stay was 2 days in both groups. No significant difference was seen in the positive margin rate (ICG, 6% vs control, 8.5%; P = .69) or observed Clavien grade III-IV complications in these 2 cohorts (ICG, 4% vs control, 15%; P = .07). No adverse events were associated with ICG dye administration. Differential ICG uptake was observed with selective clamping or in patients with cystic tumors, hypofluorescent tumors with exophytic components, and angiomyelolipomas, but these benefits could not be quantified. NIRF-ICG was transiently helpful to identify the vascular anatomy and not helpful at all for endophytic tumors. RPN using NIRF-ICG can be performed safely and effectively. A decreased warm ischemia time in the ICG cohort was observed without specific measured advantages. Differential ICG uptake by different tumors did not lead to significant differences in the positive margin rate. Copyright © 2012 Elsevier Inc. All rights reserved.

Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly.

PubMed

Parkinson, C; Renehan, A G; Ryder, W D J; O'Dwyer, S T; Shalet, S M; Trainer, P J

2002-07-01

In patients with acromegaly serum IGF-I is increasingly used as a marker of disease activity. As a result, the relationship between serum GH and IGF-I is of profound interest. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and women with GH deficiency require 30-50% more exogenous GH to maintain the same serum IGF-I as GH-deficient men. In a selected cohort of patients with active acromegaly, studied off medical therapy using a single fasting serum GH and IGF-I measurement, we have reported previously that, for a given GH level, women have significantly lower circulating IGF-I. To evaluate the influence of age and gender on the relationship between serum GH and IGF-I in an unselected cohort of patients with acromegaly independent of disease control and medical therapy. Sixty (34 male) unselected patients with acromegaly (median age 51 years (range 24-81 years) attending a colonoscopy screening programme were studied. Forty-five had previously received pituitary radiotherapy. Patients had varying degrees of disease control and received medical therapy where appropriate. Mean serum GH was calculated from an eight-point day profile (n = 45) and values obtained during a 75-g oral glucose tolerance test (n = 15). Serum IGF-I, IGFBP-3 and acid-labile subunit were measured and the dependency of these factors on covariates such as log10 mean serum GH, sex, age and prior radiotherapy was assessed using regression techniques. The median calculated GH value was 4.7 mU/l (range 1-104). A significant linear association was observed between serum IGF-I and log10 mean serum GH for the cohort (R = 0.5, P < 0.0001). After simultaneous adjustment of the above covariates a significant difference in the relationship between mean serum GH and IGF-I was observed for males and females. On average, women had serum IGF-I levels 11.44 nmol/l lower than men with the same mean serum GH (P = 0.03, 95% CI 1.33-21.4 nmol/l). Age significantly influenced the relationship and for a given serum GH, IGF-I was estimated to fall by 0.37 nmol/l per year (P = 0.04, 95% CI 0.015-0.72). In keeping with previous observations of relative GH resistance in normal and GH-deficient females we have observed lower serum IGF-I levels for equivalent mean serum GH levels in females patients with acromegaly. This gender-dependent difference is independent of disease activity and the use of concomitant medical therapy. Additionally, we have demonstrated that for a given serum GH level, age significantly influences IGF-I concentrations in patients with acromegaly. These data have important implications for the use of serum IGF-I and GH as markers of disease activity in acromegaly.

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

PubMed

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

PubMed

Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

2016-02-01

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

Analysis of abnormalities in pituitary gland in non-missile head injury: study of 100 consecutive cases.

PubMed Central

Harper, C G; Doyle, D; Adams, J H; Graham, D I

1986-01-01

Pituitary glands, obtained at necropsy from a consecutive series of 100 patients who had died as a result of non-missile head injuries, were examined to define the incidence and pathogenesis of abnormality. Images PMID:3734113

Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

PubMed Central

Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

2016-01-01

Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

Rapid Automated Quantification of Cerebral Leukoaraiosis on CT Images: A Multicenter Validation Study.

PubMed

Chen, Liang; Carlton Jones, Anoma Lalani; Mair, Grant; Patel, Rajiv; Gontsarova, Anastasia; Ganesalingam, Jeban; Math, Nikhil; Dawson, Angela; Aweid, Basaam; Cohen, David; Mehta, Amrish; Wardlaw, Joanna; Rueckert, Daniel; Bentley, Paul

2018-05-15

Purpose To validate a random forest method for segmenting cerebral white matter lesions (WMLs) on computed tomographic (CT) images in a multicenter cohort of patients with acute ischemic stroke, by comparison with fluid-attenuated recovery (FLAIR) magnetic resonance (MR) images and expert consensus. Materials and Methods A retrospective sample of 1082 acute ischemic stroke cases was obtained that was composed of unselected patients who were treated with thrombolysis or who were undergoing contemporaneous MR imaging and CT, and a subset of International Stroke Thrombolysis-3 trial participants. Automated delineations of WML on images were validated relative to experts' manual tracings on CT images, and co-registered FLAIR MR imaging, and ratings were performed by using two conventional ordinal scales. Analyses included correlations between CT and MR imaging volumes, and agreements between automated and expert ratings. Results Automated WML volumes correlated strongly with expert-delineated WML volumes at MR imaging and CT (r 2 = 0.85 and 0.71 respectively; P < .001). Spatial-similarity of automated maps, relative to WML MR imaging, was not significantly different to that of expert WML tracings on CT images. Individual expert WML volumes at CT correlated well with each other (r 2 = 0.85), but varied widely (range, 91% of mean estimate; median estimate, 11 mL; range of estimated ranges, 0.2-68 mL). Agreements (κ) between automated ratings and consensus ratings were 0.60 (Wahlund system) and 0.64 (van Swieten system) compared with agreements between individual pairs of experts of 0.51 and 0.67, respectively, for the two rating systems (P < .01 for Wahlund system comparison of agreements). Accuracy was unaffected by established infarction, acute ischemic changes, or atrophy (P > .05). Automated preprocessing failure rate was 4%; rating errors occurred in a further 4%. Total automated processing time averaged 109 seconds (range, 79-140 seconds). Conclusion An automated method for quantifying CT cerebral white matter lesions achieves a similar accuracy to experts in unselected and multicenter cohorts. © RSNA, 2018 Online supplemental material is available for this article.

Effect of early oral feeding on length of hospital stay following gastrectomy for gastric cancer: a Japanese multicenter, randomized controlled trial.

PubMed

Shimizu, Nobuyuki; Oki, Eiji; Tanizawa, Yutaka; Suzuki, Yutaka; Aikou, Susumu; Kunisaki, Chikara; Tsuchiya, Takashi; Fukushima, Ryoji; Doki, Yuichiro; Natsugoe, Shoji; Nishida, Yasunori; Morita, Masaru; Hirabayashi, Naoki; Hatao, Fumihiko; Takahashi, Ikuo; Choda, Yasuhiro; Iwasaki, Yoshiaki; Seto, Yasuyuki

2018-05-02

This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay. The subjects of this study were patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for gastric cancer between January 2014 and December 2015. Patients were randomly assigned to the early oral feeding group (intervention group) or the conventional postoperative management group (control group) for each procedure. We evaluated the length of postoperative hospital stay and the incidence of postoperative complications in each group. No significant differences in length of postoperative stay were found between the intervention and control groups of the patients who underwent DG. The incidence of postoperative complications was significantly greater in the DG intervention group. In contrast, the length of postoperative stay was significantly shorter in the TG intervention group, although the TG group did not attain the established target sample size. Early oral feeding did not shorten the postoperative hospital stay after DG. The higher incidence of postoperative complications precluded the unselected adoption of early oral feeding for DG patients. Further confirmative studies are required to definitively establish the potential benefits of early oral feeding for TG patients.

A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer

PubMed Central

Santa-Maria, Cesar August; Kato, Taigo; Park, Jae-Hyun; Kiyotani, Kazuma; Rademaker, Alfred; Shah, Ami N.; Gross, Leeaht; Blanco, Luis Z.; Jain, Sarika; Flaum, Lisa; Tellez, Claudia; Stein, Regina; Uthe, Regina; Gradishar, William J.; Cristofanilli, Massimo; Nakamura, Yusuke; Giles, Francis J.

2018-01-01

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of CD8, granzyme A, and perforin 1 gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, p = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy. PMID:29721177

Salpingitis Isthmica Nodosa: Technical Success and Outcome of Fluoroscopic Transcervical Fallopian Tube Recanalization

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

Houston, J. Graeme; Machan, Lindsay S.

1998-01-15

Purpose: To evaluate the technical success and outcome of fallopian tube recanalization (FTR) in salpingitis isthmica nodosa (SIN). Methods: SIN is a well-recognized pathological condition affecting the proximal fallopian tube and is associated with infertility and ectopic pregnancy. We reviewed the presentations, films, and case records of all patients attending for FTR for infertility from 1990 to 1994. Technical success and total, intrauterine, and ectopic pregnancy rates at follow-up were determined. Results: SIN was observed in 22 of 349 (6%) patients. FTR was attempted in 34 tubes in these 22 patients. Technical success was achieved in 23 of 34 (68%)more » tubes affected by SIN. In 5 of the 11 failed recanalizations, failure was due to distal obstruction. At least one tube was patent on selective postprocedural salpingography in 17 of 22 (77%) patients. There were no recorded perforations or complications. At follow-up (mean 14 months), total, intrauterine, and ectopic pregnancy rates were 23%, 18%, and 4.5%, respectively. Conclusion: FTR in SIN is technically successful and, compared with previously reported results in unselected infertility patients, is associated with only a slightly less favorable intrauterine pregnancy rate and a comparable ectopic pregnancy rate. The findings of SIN at FTR should not discourage attempted fluoroscopic transcervical recanalization.« less

Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

PubMed

Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

2016-03-01

DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

Lead-related complications after DDD pacemaker implantation.

PubMed

Dębski, Maciej; Ulman, Mateusz; Ząbek, Andrzej; Boczar, Krzysztof; Haberka, Kazimierz; Kuniewicz, Marcin; Lelakowski, Jacek; Małecka, Barbara

2018-04-10

Pacing leads remain the weakest link in pacemaker systems despite advances in manufacturing technology. To assess the long-term pacing lead performance in an unselected real-life cohort following primary DDD pacing system implantation. A single-centre retrospective analysis of patients who underwent DDD pacing system implantation between October 1984 and December 2014 and were followed up until August 2016 was conducted. The inclusion criterion was at least one follow-up visit following post-implant discharge. The performance of each atrial and ventricular lead implanted was evaluated during the follow-up period, and the incidence of and predictive factors for lead dislodgement and failure were analysed. The data of 3771 patients and 24431.8 patient-years of follow-up were analysed. The mean follow-up of patients was 77.7 ± 61.8 months. During the study period, 7887 transvenous atrial and right ventricular pacing leads were implanted. Lead dislodgement occurred in 94 (1.2%) leads [92 (2.4%) patients], perforation in 11 (0.1%) leads [10 (0.3%) patients] and lead failure in 329 (4.2%) leads [275 (7.3%) patients]. Atrial lead position was a predictive factor for lead dislodgement, while age at implantation, polyurethane 80A insulation, subclavian vein access, unipolar lead construction and lead manufacturer were multivariate predictors of lead failure. Leads with polyurethane 80A insulation, unipolar construction and implantation via subclavian vein puncture exhibited the worst long-term performance.

Brief Report: Severe Inflammation Following Vaccination Against Streptococcus pneumoniae in Patients With Cryopyrin-Associated Periodic Syndromes.

PubMed

Walker, Ulrich A; Hoffman, Hal M; Williams, Rene; Kuemmerle-Deschner, Jasmin; Hawkins, Philip N

2016-02-01

Pneumococcal vaccination is recommended for patients receiving immunosuppressive drugs. We describe unusually severe adverse reactions to pneumococcal vaccination in each of 7 consecutive patients with cryopyrin-associated periodic syndromes (CAPS). Seven consecutive patients with CAPS were vaccinated with pneumococcal polysaccharide or conjugate vaccines. Clinical information was collected retrospectively. Within a few hours after the vaccination, all 7 patients developed severe local reactions at the injection site. Two patients had to be hospitalized for systemic reactions including fever. All symptoms resolved in a period of 3-17 days. Our findings indicate that pneumococcal vaccines can trigger a severe local and systemic inflammatory reaction in patients with CAPS and possibly patients with other autoinflammatory diseases. Careful consideration is warranted when implementing current European League Against Rheumatism immunization guidelines in this patient population. © 2015, American College of Rheumatology.

Androgen excess in women: experience with over 1000 consecutive patients.

PubMed

Azziz, R; Sanchez, L A; Knochenhauer, E S; Moran, C; Lazenby, J; Stephens, K C; Taylor, K; Boots, L R

2004-02-01

The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinically evident androgen excess and to document the degree of long-term success of suppressive and/or antiandrogen hormonal therapy in a large consecutive population of patients. All patients presenting for evaluation of symptoms potentially related to androgen excess between October 1987 and June 2002 were evaluated, and the data were maintained prospectively in a computerized database. For the assessment of therapeutic response, a retrospective review of the medical chart was performed, after the exclusion of those patients seeking fertility therapy only, or with inadequate follow-up or poor compliance. A total of 1281 consecutive patients were seen during the study period. Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status, determine ovulatory status, or find any evidence of androgen excess. In the remaining population of 873 patients, the unbiased prevalence of androgen-secreting neoplasms was 0.2%, 21-hydroxylase-deficient classic adrenal hyperplasia (CAH) was 0.6%, 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) was 1.6%, hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome was 3.1%, idiopathic hirsutism was 4.7%, and polycystic ovary syndrome (PCOS) was 82.0%. Fifty-nine (6.75%) patients had elevated androgen levels and hirsutism but normal ovulation. A total of 257 patients were included in the assessment of the response to hormonal therapy. The mean duration of follow-up was 33.5 months (range, 6-155). Hirsutism improved in 86%, menstrual dysfunction in 80%, acne in 81%, and hair loss in 33% of patients. The major side effects noted were irregular vaginal bleeding (16.1%), nausea (13.0%), and headaches (12.6%); only 36.6% of patients never complained of side effects. In this large study of consecutive patients presenting with clinically evident androgen excess, specific identifiable disorders (NCAH, CAH, HAIRAN syndrome, and androgen-secreting neoplasms) were observed in approximately 7% of subjects, whereas functional androgen excess, principally PCOS, was observed in the remainder. Hirsutism, menstrual dysfunction, or acne, but not alopecia, improved in the majority of patients treated with a combination suppressive therapy; although more than 60% experienced side effects.

Does Postoperative Erythropoietin Reduce Transfusions and Hemodynamic Instability Following Liposuction, Either Alone or Associated with Abdominoplasty or Mammaplasty? A Comparative, Prospective Study of 50 Consecutive Patients.

PubMed

Rosique, Rodrigo G; Rosique, Marina J F; Rabelo, Mariana Quintino

2017-02-01

Erythropoietin (EPO) is a hematopoietic growth factor and an alternative to avoid blood transfusion in high-blood-loss surgeries. We evaluate EPO efficacy to reduce clinically relevant anemia and dehydration in patients undergoing liposuction. We prospectively evaluated 50 consecutive patients subjected to liposuction greater than 2.5 L and alternately assigned into two comparable groups (25 patients each), except for the postoperative administration of erythropoietin (4000 UI per day subcutaneously) during five consecutive days. Incidence data for blood transfusion or parenteral hydration were collected. Statistical analyses were performed with significance at p value <5%. There was no significant difference between groups related to any preoperative feature or the incidence of dehydration (p = 0.1099) or transfusion (p = 1.0). Postoperative erythropoietin administration was not effective in preventing blood transfusion for anemia or parenteral hydration for hemodynamic instability in patients undergoing major liposuction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Contamination of Ambient Air with Acinetobacter baumannii on Consecutive Inpatient Days.

PubMed

Shimose, Luis A; Doi, Yohei; Bonomo, Robert A; De Pascale, Dennise; Viau, Roberto A; Cleary, Timothy; Namias, Nicholas; Kett, Daniel H; Munoz-Price, L Silvia

2015-07-01

Acinetobacter-positive patients had their ambient air tested for up to 10 consecutive days. The air was Acinetobacter positive for an average of 21% of the days; the rate of contamination was higher among patients colonized in the rectum than in the airways (relative risk [RR], 2.35; P = 0.006). Of the 6 air/clinical isolate pairs available, 4 pairs were closely related according to rep-PCR results. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Comparison of Phenotypic Value Changes in Pure Lines of Bombyx mori (Lepidoptera: Bombycidae) During Consecutive Generations Following Initial Selection on Cocoon Weight

PubMed Central

Seidavi, Alireza; Goldsmith, Marian R.

2014-01-01

Abstract The experiments reported here were conducted to investigate the effect of selection on three quantitative traits, namely cocoon weight, cocoon shell weight, and cocoon shell percentage, during four generations by rearing six pure breeds of domesticated silkworm, Bombyx mori L. (Lepidoptera: Bombycidae) of Chinese and Japanese origin compared with random unselected groups as controls. All stages of rearing and data recording were performed over four rearing periods, with generations 1–3 during successive spring seasons and generation 4 during the autumn season in year 3. Each pure line contained two groups of selected and random (control) groups. Comparisons included the effect of selection methods, pure line, and generation on the phenotypic values. We found strong main effects of pure line, generation, sex, and group and support for nearly all interactions between these main effects for all three response traits. The results indicated that cocoon weight and cocoon shell weight in the selected group were higher than in the control or nonselected group. Both selected and nonselected groups had the lowest cocoon weight, cocoon shell weight, and cocoon shell percentage in the fourth generation when environmental conditions during the autumn season were less favorable than spring. The cocoon weight and cocoon shell weight averages were higher for nonselected groups in the second and third generations, and for the selected group in the first generation due to the direct effect of selection. PMID:25527593

Brain invasion assessability in meningiomas is related to meningioma size and grade, and can be improved by extensive sampling of the surgically removed meningioma specimen.

PubMed

Pizem, Joze; Velnar, Tomaz; Prestor, Borut; Mlakar, Jernej; Popovic, Mara

2014-01-01

Despite the important prognostic value of brain invasion in meningiomas, little attention has been paid to its massessment, and the parameters associated with brain invasion assessability (identification of brain tissue in the surgical specimen) are not well characterized. The aim of our study was to determine the parameters that are associated with brain invasion assessability and brain invasion in meningiomas. By binary logistic regression analysis, we studied the association of various clinical and pathologic parameters with brain invasion assessabilitym and brain invasion in 294 meningiomas: 149 unselected consecutive meningiomas with extensive sampling, diagnosed in 2009 and 2010, collected prospectively, and 145 meningiomas diagnosed in 1999 and 2000 when little attention was paid to brain invasion assessment. Meningioma grade, size and number of tissue blocks were independent predictors of brain invasion assessability. Brain tissue was identified in 78 of 233 (33%) benign, 33 of 51 (65%) atypical, and 10 of 10 (100%) malignant meningiomas. In univariate analysis, group (prospective vs.retrospective), type (recurrent vs. primary), cleavability, meningioma grade and mitotic count were predictors of brain invasion, while only meningioma grade, and group retained predictive value in multivariate analysis. Brain invasion, when assessable, was identified in 22 of 78 (28%) benign, 21 of 33 (64%) atypical, and 10 of 10 (100%) malignant meningiomas. Brain invasion assessability is related to meningioma grade and size and can be improved by extensive sampling of meningioma surgical.

The Submerged Dyslexia Iceberg: How Many School Children Are Not Diagnosed? Results from an Italian Study

PubMed Central

Barbiero, Chiara; Lonciari, Isabella; Montico, Marcella; Monasta, Lorenzo; Penge, Roberta; Vio, Claudio; Tressoldi, Patrizio Emanuele; Ferluga, Valentina; Bigoni, Anna; Tullio, Alessia; Carrozzi, Marco; Ronfani, Luca

2012-01-01

Background Although dyslexia is one of the most common neurobehavioral disorders affecting children, prevalence is uncertain and available data are scanty and dated. The objective of this study is to evaluate the prevalence of dyslexia in an unselected school population using clearly defined and rigorous diagnostic criteria and methods. Methods Cross sectional study. We selected a random cluster sample of 94 fourth grade elementary school classes of Friuli Venezia Giulia, a Region of North Eastern Italy. We carried out three consecutive levels of screening: the first two at school and the last at the Neuropsychiatry Unit of a third level Mother and Child Hospital. The main outcome measure was the prevalence of dyslexia, defined as the number of children positive to the third level of screening divided by the total number of children enrolled. Results We recruited 1774 children aged 8–10 years, of which 1528 received parents’ consent to participate. After applying exclusion criteria, 1357 pupils constituted the final working sample. The prevalence of dyslexia in the enrolled population ranged from 3.1% (95% CI 2.2–4.1%) to 3.2% (95% CI 2.4–4.3%) depending on different criteria adopted. In two out of three children with dyslexia the disorder had not been previously diagnosed. Conclusions This study shows that dyslexia is largely underestimated in Italy and underlines the need for reliable information on prevalence, in order to better allocate resources both to Health Services and Schools. PMID:23118930

Application of interactive motion charts for displaying liver transplantation data in public websites.

PubMed

Santori, G

2014-09-01

In the past several years a vast amount of digital information has become available in every field of science, and ideas to apply improved strategies for obtaining a more in-depth knowledge of the data are considered in many areas. Although several American and European organizations show regularly in their public websites the aggregated results of organ donation and transplantation, no tools are provided to engage with the final users and to enable them to handle these data. In this study, a new model of Web-based interactive motion charts was applied to aggregated liver transplantation data obtained from a consecutive 28-year series of liver transplantation performed in a single Italian center. The interactive charts were obtained by combining the Google visualization application programming interface and the googleVis package within the open source statistical environment R. The interactive charts may be embedded into online/offline Web pages and rendered in each common browser. The users may interact with the charts by selecting chart type (bubble, bar, or line chart), x- and y-axis scales (linear or logarithmic), variables, bubble size, color, and even changing opacity of unselected items. Moreover, the charts may dynamically display the trend over time of each continuous/categoric variable, allowing users both to trace how the lines changes over time and to control the animation speed. The interactive motion charts should be used in the public websites that manage aggregated data concerning organ donation and transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age.

PubMed

Malphettes, Marion; Carcelain, Guislaine; Saint-Mezard, Pierre; Leblond, Véronique; Altes, Hester Korthals; Marolleau, Jean-Pierre; Debré, Patrice; Brouet, Jean-Claude; Fermand, Jean-Paul; Autran, Brigitte

2003-03-01

Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 10(6)/kg; P =.002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+ subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L-. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.

Estimated home ranges can misrepresent habitat relationships on patchy landscapes

USGS Publications Warehouse

Mitchell, M.S.; Powell, R.A.

2008-01-01

Home ranges of animals are generally structured by the selective use of resource-bearing patches that comprise habitat. Based on this concept, home ranges of animals estimated from location data are commonly used to infer habitat relationships. Because home ranges estimated from animal locations are largely continuous in space, the resource-bearing patches selected by an animal from a fragmented distribution of patches would be difficult to discern; unselected patches included in the home range estimate would bias an understanding of important habitat relationships. To evaluate potential for this bias, we generated simulated home ranges based on optimal selection of resource-bearing patches across a series of simulated resource distributions that varied in the spatial continuity of resources. For simulated home ranges where selected patches were spatially disjunct, we included interstitial, unselected cells most likely to be traveled by an animal moving among selected patches. We compared characteristics of the simulated home ranges with and without interstitial patches to evaluate how insights derived from field estimates can differ from actual characteristics of home ranges, depending on patchiness of landscapes. Our results showed that contiguous home range estimates could lead to misleading insights on the quality, size, resource content, and efficiency of home ranges, proportional to the spatial discontinuity of resource-bearing patches. We conclude the potential bias of including unselected, largely irrelevant patches in the field estimates of home ranges of animals can be high, particularly for home range estimators that assume uniform use of space within home range boundaries. Thus, inferences about the habitat relationships that ultimately define an animal's home range can be misleading where animals occupy landscapes with patchily distributed resources.

Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer

PubMed Central

Glenn, Wendy K.; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J.; Lawson, James S.

2012-01-01

Background The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. Materials and Methods All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). Results EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk – EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. Conclusions We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer. PMID:23183846

Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

PubMed

Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

2012-01-01

The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

Maternal use of probiotics during pregnancy and effects on their offspring's health in an unselected population.

PubMed

Rutten, Nicole; Van der Gugten, Anne; Uiterwaal, Cuno; Vlieger, Arine; Rijkers, Ger; Van der Ent, Kors

2016-02-01

Probiotics are used by women in the perinatal period and may improve balance of microbiota, with possible health benefits for both mother and baby. Characteristics and (health) behaviour patterns of mothers using probiotics during pregnancy, and health effects on their offspring, were investigated. Differences between mothers using probiotics during pregnancy and those who did not, were assessed. In total, 341 out of 2491 (13.7%) mothers reported use of probiotics during pregnancy. There were no significant differences in maternal features (gestation, age, ethnicity, education) between users and non-users. Logistic regression analyses showed that consumption of probiotics was significantly associated with use of homeopathic products [odds ratio (OR) 1.65, 95% confidence interval (CI) 1.17-2.33, p = 0.005], maternal history of smoking (OR 1.72, 95% CI 1.25-2.37, p = 0.001) and paternal history of smoking (OR 1.39, 95% CI 1.01-1.89, p = 0.05). Common disease symptoms during the first year of life in the offspring did not differ between both groups. The use of probiotics or other health-related products without doctor's prescription during pregnancy might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not seem to induce positive health effects in the offspring in an unselected population. Aberrant microbiota compositions have been detected during critical periods when early programming occurs including pregnancy and early neonatal life. Probiotics modulate intestinal microbiota composition and are associated with positive health effects. The use of probiotics or other health-related products without doctor's prescription during pregnancy is associated with and might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not induce positive health effects in the offspring in this unselected population.

Impact of ELN recommendations in the management of first-line treated chronic myeloid leukaemia patients: a French cross-sectional study.

PubMed

Etienne, Gabriel; Huguet, Francoise; Guerci-Bresler, Agnès; Nicolini, Franck E; Maloisel, Frédéric; Coiteux, Valérie; Dauriac, Charles; Carpentier, Nathalie; Bourdeix, Isabelle; Tulliez, Michel; Cony-Makhoul, Pascale

2016-07-01

The availability of tyrosine kinase inhibitors has extended therapeutic options for chronic myeloid leukaemia (CML) patients. Monitoring recommendations and clinical response goals have recently been updated. The objective of this study was to describe the profile of CML patients in chronic phase currently receiving first-line therapy, including treatment, monitoring and response kinetics. A multicentre, cross-sectional, epidemiological survey in unselected chronic phase CML patients in France attending consultations during a one-month period was performed. 438 of 697 (62·8%) reported patients were currently receiving first-line treatment and were analysed. Imatinib was the most frequently received treatment (72·4% of patients). Retrospective cytogenetic and molecular assessments at 3, 6, 12 or 18 months were available in 88·4% of patients. At the 12-month assessment, 32·2% were not in major molecular response (MMR). At last assessment, among 355 patients with duration of treatment ≥ 12 months, 91·5% had achieved MMR and 66·5% were in deep molecular response. This study, performed in everyday practice population of CML patients, suggests that monitoring of molecular responses in real-life practice is aligned with European LeukaemiaNet recommendations. The majority of patients still receiving first-line treatment are in optimal response, with a few being classified as in the warning area or responding to failure. © 2016 John Wiley & Sons Ltd.

Factors Influencing Patient Selection of a Foot and Ankle Surgeon.

PubMed

Manning, Blaine T; Bohl, Daniel D; Wang, Kevin C; Hamid, Kamran S; Holmes, George B; Lee, Simon

2017-09-01

An increasingly consumer-centric health insurance market has empowered patients to select the providers of their choice. There is a lack of studies investigating the rationale by which patients select a foot and ankle surgeon. In the present study, 824 consecutive new patients seeking treatment from 3 foot-ankle surgeons were consecutively administered an anonymous questionnaire prior to their first appointment. It included rating the importance of 15 factors regarding specialist selection on a 1 to 10 scale, with 10 designated " Very important" and 1 designated " Not important at all." The remaining questions were multiple choice regarding patient perspectives on other surgeon aspects (appointment availability, waiting room times, clinic proximity, etc). Of 824 consecutive patients administered the survey, 305 (37%) responded. Patients rated board certification (9.24 ± 1.87) and on-site imaging availability (8.48 ± 2.37)-on a 1 to 10 scale, with 10 designated "Very important- as the 2 most important criteria in choosing a foot and ankle surgeon. Patients rated advertisements as least important. Among the patients, 91% responded that a maximum of 30 minutes should elapse between clinic check-in and seeing their physician; 61% responded that a maximum of 20 minutes should elapse between clinic check-in and seeing their physician. In the context of an increasingly consumer-driven paradigm of health care delivery and reimbursement, it is important to understand patients' preferences in specialist selection. Level III: Prospective questionnaire.

Anterior cervical discectomy and fusion in the outpatient ambulatory surgery setting compared with the inpatient hospital setting: analysis of 1000 consecutive cases.

PubMed

Adamson, Tim; Godil, Saniya S; Mehrlich, Melissa; Mendenhall, Stephen; Asher, Anthony L; McGirt, Matthew J

2016-06-01

OBJECTIVE In an era of escalating health care costs and pressure to improve efficiency and cost of care, ambulatory surgery centers (ASCs) have emerged as lower-cost options for many surgical therapies. Anterior cervical discectomy and fusion (ACDF) is one of the most prevalent spine surgeries performed, and the frequency of its performance is rapidly increasing as the aging population grows. Although ASCs offer significant cost advantages over hospital-based surgical centers, concern over the safety of outpatient ACDF has slowed its adoption. The authors intended to 1) determine the safety of the first 1000 consecutive ACDF surgeries performed in their outpatient ASC, and 2) compare the safety of these outpatient ACDFs with that of consecutive ACDFs performed during the same time period in the hospital setting. METHODS A total of 1000 consecutive patients who underwent ACDF in an ACS (outpatient ACDF) and 484 consecutive patients who underwent ACDF at Vanderbilt University Hospital (inpatient ACDF) from 2006 to 2013 were included in this retrospective study of patients' medical records. Data were collected on patient demographics, comorbidities, operative details, and perioperative and 90-day morbidity. Perioperative morbidity and hospital readmission were compared between the outpatient and inpatient ACDF groups. RESULTS Of the first 1000 outpatient ACDF cases performed in the authors' ASC, 629 (62.9%) were 1-level and 365 (36.5%) were 2-level ACDFs. Mean patient age was 49.5 ± 8.6, and 484 (48.4%) were males. All patients were observed postoperatively at the ASC postanesthesia care unit (PACU) for 4 hours before being discharged home. Eight patients (0.8%) were transferred from the surgery center to the hospital postoperatively (for pain control [n = 3], chest pain and electrocardiogram changes [n = 2], intraoperative CSF leak [n = 1], postoperative hematoma [n = 1], and profound postoperative weakness and surgical reexploration [n = 1]). No perioperative deaths occurred. The 30-day hospital readmission rate was 2.2%. All 90-day surgical morbidity was similar between outpatient and inpatient cohorts for both 1-level and 2-level ACDFs. CONCLUSIONS An analysis of 1000 consecutive patients who underwent ACDF in an outpatient setting demonstrates that surgical complications occur at a low rate (1%) and can be appropriately diagnosed and managed in a 4-hour ASC PACU window. Comparison with an inpatient ACDF surgery cohort demonstrated similar results, highlighting that ACDF can be safely performed in the outpatient ambulatory surgery setting without compromising surgical safety. In an effort to decrease costs of care, surgeons can safely perform 1- and 2-level ACDFs in an ASC environment.

Study designs for identification of rare disease variants in complex diseases: the utility of family-based designs.

PubMed

Ionita-Laza, Iuliana; Ottman, Ruth

2011-11-01

The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer's disease and most cancers, sequencing affected individuals with a positive family history of the disease can be extremely advantageous for identifying rare disease variants. In contrast, for complex diseases with large values of the sibling recurrence risk ratio, sequencing unselected affected individuals may be preferable.

A Membrane-Free Neutral pH Formate Fuel Cell Enabled by a Selective Nickel Sulfide Oxygen Reduction Catalyst.

PubMed

Yan, Bing; Concannon, Nolan M; Milshtein, Jarrod D; Brushett, Fikile R; Surendranath, Yogesh

2017-06-19

Polymer electrolyte membranes employed in contemporary fuel cells severely limit device design and restrict catalyst choice, but are essential for preventing short-circuiting reactions at unselective anode and cathode catalysts. Herein, we report that nickel sulfide Ni 3 S 2 is a highly selective catalyst for the oxygen reduction reaction in the presence of 1.0 m formate. We combine this selective cathode with a carbon-supported palladium (Pd/C) anode to establish a membrane-free, room-temperature formate fuel cell that operates under benign neutral pH conditions. Proof-of-concept cells display open circuit voltages of approximately 0.7 V and peak power values greater than 1 mW cm -2 , significantly outperforming the identical device employing an unselective platinum (Pt) cathode. The work establishes the power of selective catalysis to enable versatile membrane-free fuel cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heterogeneous Photocatalysis and Photoelectrocatalysis: From Unselective Abatement of Noxious Species to Selective Production of High-Value Chemicals.

PubMed

Augugliaro, Vincenzo; Camera-Roda, Giovanni; Loddo, Vittorio; Palmisano, Giovanni; Palmisano, Leonardo; Soria, Javier; Yurdakal, Sedat

2015-05-21

Heterogeneous photocatalysis and photoelectrocatalysis have been considered as oxidation technologies to abate unselectively noxious species. This article focuses instead on the utilization of these methods for selective syntheses of organic molecules. Some promising reactions have been reported in the presence of various TiO2 samples and the important role played by the amorphous phase has been discussed. The low solubility of most of the organic compounds in water limits the utilization of photocatalysis. Dimethyl carbonate has been proposed as an alternative green organic solvent. The recovery of the products by coupling photocatalysis with pervaporation membrane technology seems to be a solution for future industrial applications. As far as photoelectrocatalysis is concerned, a decrease in recombination of the photogenerated pairs occurs, enhancing the rate of the oxidation reactions and the quantum yield. Another benefit is to avoid reaction(s) between the intermediates and the substrate, as anodic and cathodic reactions take place in different places.

Clinical presentation and management of stable coronary artery disease in Austria.

PubMed

Pichlhöfer, Otto; Maier, Manfred; Badr-Eslam, Roza; Ristl, Robin; Zebrowska, Magdalena; Lang, Irene M

2017-01-01

Cardiovascular disease is the main cause of death in Austria. However, no systematic information exists regarding characteristics and treatments of contemporary patients with stable coronary artery disease (CAD) in Austria. We assembled two retrospective physicians' databases to describe demographics, clinical profiles, and therapeutic strategies in patients with stable CAD. In addition, we compared patient profiles of secondary care internists and hospital-based cardiologists with those of general practitioners in a primary care setting outside of hospital. The study population was identified from retrospective chart review of 1020 patients from 106 primary care physicians in Austria (ProCor II registry), and was merged with a previous similar database of 1280 patients under secondary care (ProCor I registry) to yield a total patient number of 2300. Female patients with stable CAD were older, had more angina and/or heart failure symptoms, and more depression than males. Female gender, type 2 diabetes mellitus, higher CCS class and asthma/COPD were predictors of elevated heart rate, while previous coronary events/revascularization predicted a lower heart rate in multivariate analysis. There were no significant differences with regard to characteristics and management of patients of general practitioners in the primary care setting versus internists in secondary care. Characteristics and treatments of unselected patients with stable ischemic heart disease in Austria resemble the pattern of large international registries of stable ischemic heart disease, with the exception that diabetes and systemic hypertension were more prevalent.

Shift in responsibilities in diabetes care: the Nurse-Driven Diabetes In-Hospital Treatment protocol (N-DIABIT).

PubMed

Manders, I G; Stoecklein, K; Lubach, C H C; Bijl-Oeldrich, J; Nanayakkara, P W B; Rauwerda, J A; Kramer, M H H; Eekhoff, E M W

2016-06-01

To investigate the feasibility, safety and efficacy of the Nurse-Driven Diabetes In-Hospital Treatment protocol (N-DIABIT), which consists of nurse-driven correctional therapy, in addition to physician-guided basal therapy, and is carried out by trained ward nurses. Data on 210 patients with diabetes consecutively admitted in the 5-month period after the introduction of N-DIABIT (intervention group) were compared with the retrospectively collected data on 200 consecutive patients with diabetes admitted in the 5-month period before N-DIABIT was introduced (control group). Additional per-protocol analyses were performed in patients in whom mean patient-based protocol adherence was ≥ 70% (intervention subgroup, n = 173 vs. control subgroup, n = 196). There was no difference between the intervention and the control group in mean blood glucose levels (8.9 ± 0.1 and 9.1 ± 0.2 mmol/l, respectively; P = 0.38), consecutive hyperglycaemic (blood glucose ≥ 10.0 mmol/l) episodes; P = 0.15), admission duration (P = 0.79), mean number of blood glucose measurements (P = 0.21) and incidence of severe hypoglycaemia (P = 0.29). Per-protocol analyses showed significant reductions in mean blood glucose levels and consecutive hypoglycaemia and hyperglycaemia in the intervention compared with the control group. Implementation of N-DIABIT by trained ward nurses in non-intensive care unit diabetes care is feasible, safe and non-inferior to physician-driven care alone. High protocol adherence was associated with improved glycaemic control. © 2015 Diabetes UK.

[Treatment of acromegaly with octreotide LAR].

PubMed

Sosa, Ernesto; Espinosa-de-los-Monteros, Ana Laura; González, Baldomero; Vargas, Guadalupe; Mier, Fernando; Mercado, Moisés

2008-01-01

Treatment of acromegaly with somastostatin analogues, albeit highly effective, is not curative and its elevated cost represents a major disadvantage. Hereby we describe our Center's experience using a fixed, 20 mg q.4 weeks- dose of octreotide LAR. 97 patients, 69 females, 71 with macroadenomas, treated with 20-mg im injections of octreotide LAR every 4 weeks, in 23 as primary therapy. No dose escalation was allowed. Patients were evaluated with GH and IGF-1 levels at 4 weeks after the third injection; thereafter, assessments occurred at 3 to 6 months intervals. In 27 unselected patients, evaluations were also performed 6 weeks after the SA injection. A GH concentration < 2.5 ng/mL was reached by 71%, 75% and 83% of patients at the 3rd , 6th and 12th months of follow up respectively, whereas over 30% achieved an IGF-1 index < or = 1.0 at each of these time points, and both biochemical goals were achieved by 30%, 33% and 32% of patients at the same time points. Biochemical success was the same for those patients treated primarily and those treated secondarily and prior radiation made no difference. A baseline GH level > 10 ng/mL was associated with a poor response. A biochemical control rate comparable with other published series it is feasible to reach with the treatment with a fixed dose of 20 mg.

Ovarian Epithelial Inclusions With Mucinous Differentiation: A Clinicopathologic Study of 42 Cases.

PubMed

Seidman, Jeffrey D; Krishnan, Jayashree

2017-07-01

Ovarian epithelial inclusions lined by mucinous epithelium are rare and of uncertain origin. Ovaries containing such inclusions were studied in 42 women. The inclusions were divided into 3 groups: serous epithelial lined with typical ciliated morphology but with distinct basophilic cytoplasmic mucin in some or all of the lining cells, those lined by typical mucinous epithelium, and those lined by a combination of typical mucinous epithelium and serous epithelium. The mean patient age was 61.5 years. Pure mucinous inclusions were found in 27 patients, serous-type inclusions with cytoplasmic mucin in 20, and mixed type in 10. All 3 types of inclusions were found in 1 patient. Two types of inclusions were found in 13. Four patients had associated mucinous neoplasms (1 mucinous cystadenoma, 1 atypical proliferative seromucinous tumor, and 2 seromucinous cystadenomas), and 11 patients (26%) had endometriosis. The fallopian tubes in 4 patients (9.5%) also displayed mucinous metaplasia; this was not significantly different from the 3.1% we found in our previously reported series of unselected tubes from the same population. These findings suggest that mucinous inclusions may arise as a direct metaplastic change in serous-type inclusions. Other possible origins of mucinous inclusions in the ovarian cortex include endometriosis and Brenner (transitional cell) nests. Whether such inclusions can be a source of mucinous ovarian neoplasms as are Brenner tumors and mature cystic teratomas is unknown and may warrant further investigation.

Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type.

PubMed

Hutton, Saunie M; Spritz, Richard A

2008-10-01

Oculocutaneous albinism (OCA) is a genetically heterogeneous group of disorders characterized by absent or reduced pigmentation of the skin, hair, and eyes. In humans, four genes have been associated with "classical" OCA and another 12 genes with syndromic forms of OCA. To assess the prevalence of different forms of OCA and different gene mutations among non-Hispanic Caucasian patients, we performed DNA sequence analysis of the four genes associated with "classical" OCA (TYR, OCA2, TYRP1, SLC45A2), the two principal genes associated with syndromic OCA (HPS1, HPS4), and a candidate OCA gene (SILV), in 121 unrelated, unselected non-Hispanic/Latino Caucasian patients carrying the clinical diagnosis of OCA. We identified apparent pathologic TYR gene mutations in 69% of patients, OCA2 mutations in 18%, SLC45A2 mutations in 6%, and no apparent pathological mutations in 7% of patients. We found no mutations of TYRP1, HPS1, HPS4, or SILV in any patients. Although we observed a diversity of mutations for each gene, a relatively small number of different mutant alleles account for a majority of the total. This study demonstrates that, contrary to long-held clinical lore, OCA1, not OCA2, is by far the most frequent cause of OCA among Caucasian patients.

Incidence and diagnosis of anosognosia for hemiparesis revisited

PubMed Central

Baier, B; Karnath, H

2005-01-01

Background: In previous studies, the incidence of anosognosia for hemiparesis has varied between 17% and 58% in samples of brain damaged patients with hemiparesis. Objective: To determine whether this wide variation might be explained by the different criteria used for diagnosing anosognosia. Methods: 128 acute stroke patients with hemiparesis or hemiplegia were tested for anosognosia for hemiparesis using the anosognosia scale of Bisiach et al. Results: 94% of the patients who were rated as having "mild anosognosia"—that is, they did not acknowledge their hemiparesis spontaneously following a general question about their complaints—suffered from, and mentioned, other neurological deficits such as dysarthria, ptosis, or headache. However, they immediately acknowledged their paresis when they were asked about the strength of their limbs. Their other deficits clearly had a greater impact. These patients had significantly milder paresis than those who denied their disorder even when asked directly about their limbs. Conclusions: Patients who do not mention their paresis spontaneously but do so when questioned about it directly should not be diagnosed having "anosognosia." If this more conservative cut off criterion is applied to the data of the present as well as previous studies, a frequency of between 10% and 18% for anosognosia for hemiparesis is obtained in unselected samples of acute hemiparetic stroke patients. The incidence thus seems smaller than previously assumed. PMID:15716526

Method of Breast Reconstruction Determines Venous Thromboembolism Risk Better Than Current Prediction Models

PubMed Central

Patel, Niyant V.; Wagner, Douglas S.

2015-01-01

Background: Venous thromboembolism (VTE) risk models including the Davison risk score and the 2005 Caprini risk assessment model have been validated in plastic surgery patients. However, their utility and predictive value in breast reconstruction has not been well described. We sought to determine the utility of current VTE risk models in this population and the VTE rate observed in various methods of breast reconstruction. Methods: A retrospective review of breast reconstructions by a single surgeon was performed. One hundred consecutive transverse rectus abdominis myocutaneous (TRAM) patients, 100 consecutive implant patients, and 100 consecutive latissimus dorsi patients were identified over a 10-year period. Patient demographics and presence of symptomatic VTE were collected. 2005 Caprini risk scores and Davison risk scores were calculated for each patient. Results: The TRAM reconstruction group was found to have a higher VTE rate (6%) than the implant (0%) and latissimus (0%) reconstruction groups (P < 0.01). Mean Davison risk scores and 2005 Caprini scores were similar across all reconstruction groups (P > 0.1). The vast majority of patients were stratified as high risk (87.3%) by the VTE risk models. However, only TRAM reconstruction patients demonstrated significant VTE risk. Conclusions: TRAM reconstruction appears to have a significantly higher risk of VTE than both implant and latissimus reconstruction. Current risk models do not effectively stratify breast reconstruction patients at risk for VTE. The method of breast reconstruction appears to have a significant role in patients’ VTE risk. PMID:26090287

Use of cumulative mortality data in patients with acute myocardial infarction for early detection of variation in clinical practice: observational study.

PubMed

Lawrance, R A; Dorsch, M F; Sapsford, R J; Mackintosh, A F; Greenwood, D C; Jackson, B M; Morrell, C; Robinson, M B; Hall, A S

2001-08-11

Use of cumulative mortality adjusted for case mix in patients with acute myocardial infarction for early detection of variation in clinical practice. Observational study. 20 hospitals across the former Yorkshire region. All 2153 consecutive patients with confirmed acute myocardial infarction identified during three months. Variable life-adjusted displays showing cumulative differences between observed and expected mortality of patients; expected mortality calculated from risk model based on admission characteristics of age, heart rate, and systolic blood pressure. The performance of two individual hospitals over three months was examined as an example. One, the smallest district hospital in the region, had a series of 30 consecutive patients but had five more deaths than predicted. The variable life-adjusted display showed minimal variation from that predicted for the first 15 patients followed by a run of unexpectedly high mortality. The second example was the main tertiary referral centre for the region, which admitted 188 consecutive patients. The display showed a period of apparently poor performance followed by substantial improvement, where the plot rose steadily from a cumulative net lives saved of -4 to 7. These variations in patient outcome are unlikely to have been revealed during conventional audit practice. Variable life-adjusted display has been integrated into surgical care as a graphical display of risk-adjusted survival for individual surgeons or centres. In combination with a simple risk model, it may have a role in monitoring performance and outcome in patients with acute myocardial infarction.

Use of Autologous Scleral Graft in Ahmed Glaucoma Valve Surgery.

PubMed

Wolf, Alvit; Hod, Yair; Buckman, Gila; Stein, Nili; Geyer, Orna

2016-04-01

To compare the efficacy of an autoscleral free-flap graft versus an autoscleral rotational flap graft in Ahmed glaucoma valve (AGV) surgery. Medical records (2005 to 2012) of 51 consecutive patients (51 eyes) who underwent AGV surgery with the use of either an autoscleral free-flap graft or an autoscleral rotational flap graft to cover the external tube at the limbus were retrieved for review. The main outcome measure was the incidence of tube exposure associated with each surgical approach. Twenty-seven consecutive patients (27 eyes) received a free-flap graft and 24 consecutive patients (24 eyes) received a rotational flap graft. The mean follow-up time was 55.6 ± 18.3 months for the former and 24.2± 5 .0 months for the latter (P<0.0001). Two patients in the free-flap group (8.9%) developed tube exposure at 24 and 55 months postoperatively compared with none of the patients in the rotational flap group. Graft thinning without evidence of conjunctival erosion was observed in 15 patients (55%) in the free-flap group and in 7 patients (29.1%) in the rotational flap group. The use of an autoscleral rotational flap graft is an efficacious technique for primary tube patch grafting in routine AGV surgery, and yielded better results than an autoscleral free-flap graft. Its main advantages over donor graft material are availability and lower cost.

Impact of robotics on the outcome of elderly patients with endometrial cancer.

PubMed

Lavoue, Vincent; Zeng, Xing; Lau, Susie; Press, Joshua Z; Abitbol, Jeremie; Gotlieb, Raphael; How, Jeffrey; Wang, Yifan; Gotlieb, Walter H

2014-06-01

To evaluate the impact of introducing a robotics program on clinical outcome of elderly patients with endometrial cancer. Evaluation and comparison of peri-operative morbidity and disease-free interval in 163 consecutive elderly patients (≥70years) with endometrial cancer undergoing staging procedure with traditional open surgery compared to robotic surgery. All consecutive patients ≥70years of age with endometrial cancer who underwent robotic surgery (n=113) were compared with all consecutive patients ≥70years of age (n=50) before the introduction of a robotic program in December 2007. Baseline patient characteristics were similar in both eras. Patients undergoing robotic surgery had longer mean operating times (244 compared with 217minutes, p=0.009) but fewer minor adverse events (17% compared with 60%, p<0.001). The robotics cohort had less estimated mean blood loss (75 vs 334mL, p<0.0001) and shorter mean hospital stay (3 vs 6days, p<0.0001). There was no difference in disease-free survival (p=0.61) during the mean follow-up time of 2years. Transitioning from open surgery to a robotics program for the treatment of endometrial cancer in the elderly has significant benefits, including lower minor complication rate, less operative blood loss and shorter hospitalization without compromising 2-year disease-free survival. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of endometrial scratch on natural-cycle cryopreserved embryo transfer outcomes: a randomized controlled study.

PubMed

Mak, Jennifer Sze Man; Chung, Cathy Hoi Sze; Chung, Jacqueline Pui Wah; Kong, Grace Wing Shan; Saravelos, Sotirios H; Cheung, Lai Ping; Li, Tin-Chiu

2017-07-01

The benefit of endometrial scratch (ES) prior to embryo transfer is controversial. Systemic analysis has confirmed its potential benefit, especially in women with repeated IVF failures, yet most studies have focused on fresh embryo transfer, and its effect on vitrified-warmed embryo transfer (FET) cycles is yet to be explored. We hereby present our prospective, double-blind, randomized controlled study on the evaluation of the implantation and pregnancy rate after ES prior to natural-cycle FET. A total of 299 patients underwent natural-cycle FET and were randomized to receive ES (n = 115) or endocervical manipulation as control (n = 114) prior to FET cycle, and a total of 196 patients had embryo transfer (93 patients in each group). Our study showed no significant difference in the implantation and pregnancy rate, as well as the clinical and ongoing pregnancy or live birth rates between the two groups. It appears that ES does not have any beneficial effect on an unselected group of women undergoing FET in natural cycles. Further studies on its effect in women with recurrent implantation failure after IVF are warranted. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Acute respiratory distress syndrome: an audit of incidence and outcome in Scottish intensive care units.

PubMed

Hughes, M; MacKirdy, F N; Ross, J; Norrie, J; Grant, I S

2003-09-01

This prospective audit of incidence and outcome of the acute respiratory distress syndrome was conducted as part of the national audit of intensive care practice in Scotland. All patients with acute respiratory distress syndrome in 23 adult intensive care units were identified using the diagnostic criteria defined by the American-European Consensus Conference. Daily data collection was continued until death or intensive care unit discharge. Three hundred and sixty-nine patients were diagnosed with acute respiratory distress syndrome over the 8-month study period. The frequency of acute respiratory distress syndrome in the intensive care unit population was 8.1%; the incidence in the Scottish population was estimated at 16.0 cases.100,000(-1).year(-1). Intensive care unit mortality for acute respiratory distress syndrome was 53.1%, with a hospital mortality of 60.9%. In our national unselected population of critically ill patients, the overall outcome is comparable with published series (Acute Physiology and Chronic Health Evaluation II standardised mortality ratio = 0.99). However, mortality from acute respiratory distress syndrome in Scotland is substantially higher than in recent other series suggesting an improvement in outcome in this condition.

Volume of hydration in terminal cancer patients.

PubMed

Bruera, E; Belzile, M; Watanabe, S; Fainsinger, R L

1996-03-01

In this retrospective study we reviewed the volume and modality of hydration of consecutive series of terminal cancer patients in two different settings. In a palliative care unit 203/290 admitted patients received subcutaneous hydration for 12 +/- 8 days at a daily volume of 1015 +/- 135 ml/day. At the cancer center, 30 consecutive similar patients received intravenous hydration for 11.5 +/- 5 days (P > 0.2) but at a daily volume of 2080 +/- 720 ml/day (P < 0.001). None of the palliative care unit patients required discontinuation of hydration because of complications. Hypodermoclysis was administered mainly as a continuous infusion, an overnight infusion, or in one to three 1-h boluses in 62 (31%), 98 (48%) and 43 (21%) patients, respectively. Our findings suggest that, in some settings, patients may be receiving excessive volumes of hydration by less comfortable routes such as the intravenous route. Increased education and research in this area are badly needed.

Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma.

PubMed

Cabello, I; Servitje, O; Corbella, X; Bardés, I; Pintó, X

2017-04-01

Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia. To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene. From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA. Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination. Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia. © 2017 British Association of Dermatologists.

Sexual Orientation in Adolescents Who Commit Suicide.

ERIC Educational Resources Information Center

Shaffer, David; And Others

1995-01-01

Examined relationship between suicidal behavior and homosexuality in adolescence in an unselected, matched sample. Found no evidence that suicide is a common characteristic of gay youth, or that when suicide does occur among gay teenagers, that it is a direct consequence of stigmatization or lack of support. (JBJ)

An Evaluation of the Navy’s Health Promotion Videotapes

DTIC Science & Technology

1990-04-30

1263. Fisher, L., Rowley, P. T., & Lipkin. M. (1981). Genetic counseling for beta- thalassemia trait following health screening in a health maintenence...counseling for x, ta- thalassemia trait in a population unselected for interest: Effects on knowledge and m ,ood. American Journal of Human Genetics

[Critical appraisal of organ procurement under Maastricht 3 condition].

PubMed

Puybasset, L; Bazin, J-E; Beloucif, S; Bizouarn, P; Crozier, S; Devalois, B; Eon, B; Fieux, F; Gisquet, E; Guibet-Lafaye, C; Kentish, N; Lienhart, A; Nicolas-Robin, A; Otero Lopez, M; Pelluchon, C; Roussin, F; Beydon, L

2012-05-01

The ethics committee of the French Society of Anesthesia and Intensive Care (Sfar) has been requested by the French Biomedical Agency to consider the issue of organ donation in patients after a decision of withdrawing life supporting therapies has been taken. This category of organ donation is performed in the USA, Canada, United Kingdom, the Netherlands and Belgium. The three former countries have published recommendations, which formalize procedures and operations. The Sfar ethics committee has considered this issue and envisioned the different aspects of the whole process. Consequently, it sounds a note of caution regarding the applicability of this type of organ procurement in unselected patient following a decision to withdraw life supporting therapies. According to the French regulation concerning organ procurement in brain dead patients, the committee stresses the need to restrict this specific way of procurement to severely brain injured patients, once confirmatory investigations predicting a catastrophic prognosis have been performed. It suggests that the nature of the confirmatory investigation required should be formalized by the French Biomedical Agency on behalf of the French parliamentarians. This should help preserving population trust regarding organ procurement and provide a framework to medical decision. This text has been endorsed by the Sfar. Copyright © 2012. Published by Elsevier SAS.

The value of radiology in predicting gallstone type when selecting patients for medical treatment.

PubMed Central

Bell, G D; Dowling, R H; Whitney, B; Sutor, D J

1975-01-01

Since medical treatment of gallstones is confined to cholesterol-rich stones, the ability of clinical radiographs to predict gallstone type was tested prospectively by comparing the preoperative radiological appearance of gallstones from 57 unselected patients with cholelithiasis coming to cholecystectomy with the subsequent analysis of the stones both by X-ray diffraction and by chemical techniques. Fifty-two per cent of the patients had 'non-functioning' gallbladders which failed to opacify after at least two contrast examinations and 25 out of 50 had radioopaque stones. Of the 25 patients with radiolucent stones, the stones in 20 ((80%) were predominantly cholesterol in type but radiology was misleading in five; three contained 40-55% calcium salts but were still radiolucent while two were amorphous and contained less than 10% cholesterol by weight on chemical analysis. While radiology was sometimes misleading when the stones were small and irregular, large radiolucent stones with a smooth profile were invariably cholesterol-rich stones. The results also show that in men calcified stones were commoner than in women and that in older women the gallstones contained more calcium salts and less cholesterol than in younger women less than 50 yr). This paper analyses critically the value and limitations of clinical radiology in predicting gallstone type. PMID:1140634

Survival After Relapse of Medulloblastoma.

PubMed

Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

2016-05-01

Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations.

The prevalence of BRCA1 and BRCA2 mutations among young Mexican women with triple-negative breast cancer

PubMed Central

Villarreal-Garza, C.; Weitzel, J. N.; Llacuachaqui, M.; Sifuentes, E.; Magallanes-Hoyos, M. C.; Gallardo, L.; Alvarez-Gómez, R. M.; Herzog, J.; Castillo, D.; Royer, R.; Akbari, Mohammad; Lara-Medina, F.; Herrera, L. A.; Mohar, A.

2015-01-01

Various guidelines recommend that women with triple-negative breast cancer should be tested for BRCA1 mutations, but the prevalence of mutations may vary with ethnic group and with geographic region, and the optimal cutoff age for testing has not been established. We estimated the frequencies of BRCA1 and BRCA2 (BRCA) mutations among 190 women with triple-negative breast cancer, unselected for family history, diagnosed at age 50 or less at a single hospital in Mexico City. Patients were screened for 115 recurrent BRCA mutations, which have been reported previously in women of Hispanic origin, including a common large rearrangement Mexican founder mutation (BRCA1 ex9-12del). A BRCA mutation was detected in 44 of 190 patients with triple-negative breast cancer (23 %). Forty-three mutations were found in BRCA1 and one mutation was found in BRCA2. Seven different mutations accounted for 39 patients (89 % of the total mutations). The Mexican founder mutation (BRCA1 ex9-12del) was found 18 times and accounted for 41 % of all mutations detected. There is a high prevalence of BRCA1 mutations among young triple-negative breast cancer patients in Mexico. Women with triple-negative breast cancer in Mexico should be screened for mutations in BRCA1. PMID:25716084

Analysis of polymorphic patterns in candidate genes in Israeli patients with prostate cancer.

PubMed

Figer, Arie; Friedman, Tal; Manguoglu, Ayse Esra; Flex, Dov; Vazina, Amnon; Novikov, Ilia; Shtrieker, Avi; Sidi, A Ami; Tichler, Thomas; Sapir, Einat Even; Baniel, Jack; Friedman, Eitan

2003-10-01

The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known. To evaluate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters. Jewish Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters. The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner. In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Mutation frequency in 15 common cancer genes in high-risk head and neck squamous cell carcinoma.

PubMed

McBride, Sean M; Rothenberg, S Michael; Faquin, William C; Chan, Annie W; Clark, John R; Ellisen, Leif W; Wirth, Lori J

2014-08-01

With prior studies having looked at unselected cohorts, we sought to explore the mutational landscape in a high-risk group of head and neck squamous cell carcinoma (HNSCC) tumors. A multiplexed polymerase chain reaction (PCR) assay evaluating 68 loci in 15 genes was performed on 64 patients with high-risk HNSCC. Because of the frequent PIK3CA and AKT1 mutations in patients with oropharyngeal carcinoma, we evaluated the relationship between mutation status and both clinical/pathologic variables and tumor control in this subgroup. Seventeen of 64 patients harbored mutations in the assayed loci: 16% in PIK3CA, 9% in TP53, 2% in AKT1, and 2% in epidermal growth factor receptor (EGFR). The frequency of PIK3CA/AKT1 mutations in oropharyngeal and sinonasal primaries was increased compared to other primary sites (35% vs 6%; p = .005). There was no relationship between mutation status and overall survival (OS), disease-specific death, or progression in the oropharyngeal cohort. We identified frequent PIK3CA mutations in patients with high-risk HNSCC confined predominantly to the oropharyngeal and sinonasal subsites; for the first time, mutation in AKT1 has been identified in HNSCC. Copyright © 2014 Wiley Periodicals, Inc.

[Institutional Prevalence and Context of Severe Sleep Disorders in Psychosomatic Rehabilitation].

PubMed

Linden, Michael

2015-07-01

In cases of burnout, chronic fatigue, depression, somatization, overtaxation, or impairment in wellbeing and work capacity, the cause can be sleep problems. Goal of the present study was to estimate the prevalence of sleep problems in psychosomatic inpatients. Included were 1325 unselected patients from a psychosomatic rehabilitation hospital. They filled in the SCL-90, the PSQI and were assessed in respect to their clinical, social and occupational status. At admission 13.4% of patients had a PSQI score of 5 at maximum (no sleep problem), 34.6% 6 to 10 (moderate sleep problem) und 52.1% over 10 (severe sleep problem). At discharge there was a reduction of sleep problems with 32.7% of patients over 10. Sleep problems were significantly associated with more severe mental problems, older age, women, lower socioeconomic status, and also incapacity to work or early retirement. Mental disorders can cause sleep problems and sleep problems mental disorders and incapacity to work, with a negative interaction. The high rate of severe sleep problems in rehabilitation patients shows that this problem is in need of special diagnostic and therapeutic attention. Also, the equipment of hospitals and the qualification of therapists should allow adequate care. © Georg Thieme Verlag KG Stuttgart · New York.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy.

PubMed

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-07-01

Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy.Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test.Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology.The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy

PubMed Central

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-01-01

Abstract Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy. Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test. Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology. The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment. PMID:26131823

Cortical processing during smartphone text messaging.

PubMed

Tatum, William O; DiCiaccio, Benedetto; Yelvington, Kirsten H

2016-06-01

The objective of this study was to report the EEG features of text messaging using smartphones. One hundred twenty-nine patients were prospectively evaluated during video-EEG monitoring (VEM) over 16months. A reproducible texting rhythm (TR) present during active text messaging with a smartphone was compared with passive and forced audio telephone use, thumb/finger movements, cognitive testing/calculation, scanning eye movements, and speech/language tasks in patients with and without epilepsy. Statistical significance was set at p<0.05. Twenty-seven patients with a TR were identified from a cohort of 129 (93 female, mean age: 36; range: 18-71) unselected VEM patients. Fifty-three out of 129 patients had epileptic seizures (ES), 74/129 had nonepileptic seizures (NES), and 2/129 were dual-diagnosed. A reproducible TR was present in 27/129 (20.9%) specific to text messaging (p<0.0001) and present in 28% of patients with ES and 16% of patients with NES (p=NS). The TR was absent during independent tasks and audio cellular telephone use (p<0.0001). Age, gender, epilepsy type, MRI results, and EEG lateralization in patients with focal seizures were unrelated (p=NS). Our results suggest that the TR on scalp EEG represents a novel technology-specific neurophysiological alteration of brain networks. We propose that cortical processing in the contemporary brain is uniquely activated by the use of PEDs. These findings have practical implications that could impact industry and research in nonverbal communication. Copyright © 2016 Elsevier Inc. All rights reserved.

Impairments in proverb interpretation following focal frontal lobe lesions.

PubMed

Murphy, Patrick; Shallice, Tim; Robinson, Gail; MacPherson, Sarah E; Turner, Martha; Woollett, Katherine; Bozzali, Marco; Cipolotti, Lisa

2013-09-01

The proverb interpretation task (PIT) is often used in clinical settings to evaluate frontal "executive" dysfunction. However, only a relatively small number of studies have investigated the relationship between frontal lobe lesions and performance on the PIT. We compared 52 patients with unselected focal frontal lobe lesions with 52 closely matched healthy controls on a proverb interpretation task. Participants also completed a battery of neuropsychological tests, including a fluid intelligence task (Raven's Advanced Progressive Matrices). Lesions were firstly analysed according to a standard left/right sub-division. Secondly, a finer-grained analysis compared the performance of patients with medial, left lateral and right lateral lesions with healthy controls. Thirdly, a contrast of specific frontal subgroups compared the performance of patients with medial lesions with patients with lateral frontal lesions. The results showed that patients with left frontal lesions were significantly impaired on the PIT, while in patients with right frontal lesions the impairments approached significance. Medial frontal patients were the only frontal subgroup impaired on the PIT, relative to healthy controls and lateral frontal patients. Interestingly, an error analysis indicated that a significantly higher number of concrete responses were found in the left lateral subgroup compared to healthy controls. We found no correlation between scores on the PIT and on the fluid intelligence task. Overall our results suggest that specific regions of the frontal lobes contribute to the performance on the PIT. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort.

PubMed

Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; Boulle, Andrew; Vogt, Monica; Gupta-Wright, Ankur; Nicol, Mark P; Meintjes, Graeme

2017-03-21

We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB. Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions. Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9-99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50-11.75). Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis.

Pegylated interferon-alpha2b plus ribavirin therapy in patients with hepatitis C and psychiatric disorders: results of a cohort study.

PubMed

Lang, Jean-Philippe; Melin, Pascal; Ouzan, Denis; Rotily, Michel; Fontanges, Thierry; Marcellin, Patrick; Chousterman, Michel; Cacoub, Patrice

2010-01-01

Hepatitis C antiviral therapies have significant psychiatric side effects. It is therefore believed that they might exacerbate mental illness in patients with pre-existing psychiatric disorders, resulting in poor adherence and response to antiviral treatment. We aimed to assess adherence to treatment, virological outcomes and mental safety in psychiatric patients, compared with non-psychiatric patients, treated for hepatitis C. A cohort study involved unselected hepatitis C patients on scheduled therapy with pegylated interferon-alpha2b and ribavirin, between 2002 and 2005 in France, and followed-up until 6 months after the end of treatment. Virological response was reported by the physician according to standard definitions and adverse events were monitored. Adherence to treatment was assessed by patient report. Among 1,860 patients, 403 (22%) had pre-existing psychiatric disorders, mostly depressive and anxiety disorders. Strict adherence was similar in psychiatric and non-psychiatric patients (35% versus 39%; P=0.20) as was the rate of sustained virological response (52% versus 51%; P=0.75). Conversely the rate of mental adverse events was higher in psychiatric patients (78% versus 57%; P<0.001). Baseline characteristics independently associated with the risk of later mental adverse events were history of depression, initial pegylated interferon-alpha2b dose and female gender. Antiviral therapy in hepatitis C patients with associated psychiatric disease appears as effective as in other patients but results in a higher rate of mental adverse events, emphasizing the need for close monitoring of these psychiatric patients.

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

PubMed

Besser, Michal J; Shapira-Frommer, Ronnie; Treves, Avraham J; Zippel, Dov; Itzhaki, Orit; Schallmach, Ester; Kubi, Adva; Shalmon, Bruria; Hardan, Izhar; Catane, Raphael; Segal, Eran; Markel, Gal; Apter, Sara; Nun, Alon Ben; Kuchuk, Iryna; Shimoni, Avichai; Nagler, Arnon; Schachter, Jacob

2009-05-01

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Diagnosis and initial management of urological injuries associated with 200 consecutive pelvic fractures.

PubMed

Palmer, J K; Benson, G S; Corriere, J N

1983-10-01

During 26 months 200 consecutive patients with fracture of the bony pelvis were evaluated and treated for urological injury. There was no correlation between the extent of pelvic injury and degree of hematuria but hematuria was present in all patients with a urological injury. All urological injuries occurred with anterior arch fractures. The over-all incidence of injury was 13.5 per cent (bladder 9 per cent, urethra 3.5 per cent and combined 1 per cent). Limited extraperitoneal bladder ruptures were treated successfully by Foley catheter drainage.

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

PubMed

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-03-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Evaluation of three sampling methods to monitor outcomes of antiretroviral treatment programmes in low- and middle-income countries.

PubMed

Tassie, Jean-Michel; Malateste, Karen; Pujades-Rodríguez, Mar; Poulet, Elisabeth; Bennett, Diane; Harries, Anthony; Mahy, Mary; Schechter, Mauro; Souteyrand, Yves; Dabis, François

2010-11-10

Retention of patients on antiretroviral therapy (ART) over time is a proxy for quality of care and an outcome indicator to monitor ART programs. Using existing databases (Antiretroviral in Lower Income Countries of the International Databases to Evaluate AIDS and Médecins Sans Frontières), we evaluated three sampling approaches to simplify the generation of outcome indicators. We used individual patient data from 27 ART sites and included 27,201 ART-naive adults (≥15 years) who initiated ART in 2005. For each site, we generated two outcome indicators at 12 months, retention on ART and proportion of patients lost to follow-up (LFU), first using all patient data and then within a smaller group of patients selected using three sampling methods (random, systematic and consecutive sampling). For each method and each site, 500 samples were generated, and the average result was compared with the unsampled value. The 95% sampling distribution (SD) was expressed as the 2.5(th) and 97.5(th) percentile values from the 500 samples. Overall, retention on ART was 76.5% (range 58.9-88.6) and the proportion of patients LFU, 13.5% (range 0.8-31.9). Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4-77.7) for random, 76.5% (75.3-77.5) for systematic and 76.0% (74.1-78.2) for the consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6-14.5), 13.5% (12.6-14.3) and 14.0% (12.5-15.5), respectively. With consecutive sampling, 50% of sites had SD within ±5% of the unsampled site value. Our results suggest that random, systematic or consecutive sampling methods are feasible for monitoring ART indicators at national level. However, sampling may not produce precise estimates in some sites.

[PERCUTANEOUS CORRECTION OF FOREFOOT DEFORMITIES IN DIABETIC PATIENTS IN ORDER TO PREVENT PRESSURE SORES - TECHNIQUE AND RESULTS IN 20 CONSECUTIVE PATIENTS].

PubMed

Yassin, Mustafa; Garti, Avraham; Heller, Eyal; Weissbrot, Moshe; Robinson, Dror

2017-04-01

Diabetes mellitus is a 21st century pandemic. Due to life-span prolongation combined with the increased rate of diabetes, a growing population of patients is afflicted with neuropathic foot deformities. Traditional operative repair of these deformities is associated with a high complication rate and relatively common infection incidence. In recent years, in order to prevent these complications, percutaneous deformity correction methods were developed. Description of experience accumulated in treating 20 consecutive patients with diabetic neuropathic foot deformities treated in a percutaneous fashion. A consecutive series of patients treated at our institute for neuropathic foot deformity was assessed according to a standard protocol using the AOFAS forefoot score and the LUMT score performed at baseline as well as at 6 months and 12 months. Treatment related complications were monitored. All procedures were performed in an ambulatory setting using local anesthesia. A total of 12 patients had soft tissue corrections, and 8 had a combined soft tissue and bone correction. Baseline AOFAS score was 48±7 and improved to 73±9 at six months and 75±7 at one year. LUMT score in 11 patients with a chronic wound decreased from 22±4 to 2±1 at one year post-op. One patient required hospitalization due to post-op bleeding. Percutaneous techniques allow deformity correction of diabetic feet, including those with open wounds in an ambulatory setting with a low complication rate.

Effect of Hypoglycemic Agents on Ischemic Preconditioning in Patients With Type 2 Diabetes and Symptomatic Coronary Artery Disease

PubMed Central

Rahmi, Rosa Maria; Uchida, Augusto Hiroshi; Rezende, Paulo Cury; Lima, Eduardo Gomes; Garzillo, Cibele Larrosa; Favarato, Desiderio; Strunz, Celia M.C.; Takiuti, Myrthes; Girardi, Priscyla; Hueb, Whady; Kalil Filho, Roberto; Ramires, José A.F.

2013-01-01

OBJECTIVE To assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS We performed a prospective study of 96 consecutive patients allocated into two groups: 42 to group repaglinide (R) and 54 to group vildagliptin (V). All patients underwent two consecutive exercise tests (ET1 and ET2) in phase 1 without drugs. In phase 2, 1 day after ET1 and -2, 2 mg repaglinide three times daily or 50 mg vildagliptin twice daily was given orally to patients in the respective group for 6 days. On the seventh day, 60 min after 6 mg repaglinide or 100 mg vildagliptin, all patients underwent two consecutive exercise tests (ET3 and ET4). RESULTS In phase 1, IPC was demonstrated by improvement in the time to 1.0 mm ST-segment depression and rate pressure product (RPP). All patients developed ischemia in ET3; however, 83.3% of patients in group R experienced ischemia earlier in ET4, without significant improvement in RPP, indicating the cessation of IPC (P < 0.0001). In group V, only 28% of patients demonstrated IPC cessation, with 72% still having the protective effect (P < 0.0069). CONCLUSIONS Repaglinide eliminated myocardial IPC, probably by its effect on the KATP channel. Vildagliptin did not damage this protective mechanism in a relevant way in patients with type 2 diabetes and CAD, suggesting a good alternative treatment in this population. PMID:23250803

Ethical decisions in dental treatment planning using the Ozar model: a descriptive study of fifty-two consecutive patients.

PubMed

Schuman, N J; Turner, J E

1997-01-01

Chairside dental ethics necessitates special consideration by the faculty member-dentist, the dental student, and the patient. The patient must always be aware of treatment options, in addition to learning the health status of the oral hard and soft tissues, costs, and time to be involved to accomplish proposed treatment. What may seem like a burden to an individual practitioner is actually only the necessities incurred by any self governing profession. Fifty-two consecutive dental patients had their cases reviewed for the ethical behavior of the dentist-practitioner, student, and patient. Categories reviewed were informed consent (100%), agreement, compromise, economic issues, conflict, and institutional issues. The results were: 1. Agreement: 17 cases, 2. Compromise: 21 cases, 3. Economic Issues: 4 cases, 4. Conflict: 6 cases, and 5. Institutional Issues: 4 cases. Fourteen percent of all patients were minors. Ninety percent of the patients were treated. Of those 10% not treated, five percent were for medical reasons, and five percent of the patients refused treatment. These results were placed in the Ozar Model 9 and were categorized as follows: 1. Appropriate pain free oral function: 22 cases, 2. Patient Autonomy: 14 cases, 3. Life and health: 9 cases, 4. Preferred practice values: 6 cases, and 5. Other external considerations: 1 case. This template demonstrated appropriate ethical behavior on the part of dentists, students, and patients, especially with a 90% treatment group, and only 5% refusing treatment. The 52 consecutive patients were characteristic of the University of Tennessee's overall patient pool. No identifiable differences were found between patients regardless of gender, age, or race.

BRCA germline mutations in women with uterine serous carcinoma--still a debate.

PubMed

Lavie, Ofer; Ben-Arie, Alon; Segev, Yakir; Faro, Jonathan; Barak, Frida; Haya, Nir; Auslender, Ron; Gemer, Ofer

2010-12-01

To determine the incidence of BRCA1 and BRCA2 mutations in an enlarged series of uterine serous carcinoma (USC) patients and to determine whether patients with USC are associated with a personal or familial history of breast or ovarian carcinoma. A cohort of all consecutive patients with diagnosed USC was identified for 9 years. Family pedigrees were drawn as far back and laterally as possible. In all patients, genomic DNA was extracted from peripheral blood samples and analyzed for the 3 mutations common in Ashkenazi Jewish patients. All patients went through total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Tubal, ovarian, and peritoneal carcinoma were ruled out clinically and pathologically in all patients. Of 51 consecutive patients with USC in Ashkenazi Jews studied, we identified 13 patients (25.5%) who were previously found to have breast carcinoma, 17 patients (33.3%) who had a first-degree relative with breast or ovarian carcinoma, and 8 patients (15.7%) who were found to be carriers of 1 of the 3 BRCA germline mutations. This series of USC patients, the largest consecutive series to date, suggests a higher incidence of BRCA carriers among Ashkenazi Jews as compared with the general population. This high rate of BRCA germline mutations in USC patients coupled with a high rate of personal and familial cancer histories may suggest that USC is associated with the hereditary breast-ovarian syndrome. This potential association of USC to the BRCA-associated cancer spectrum may have implications for the clinical management and intervention of unaffected BRCA1-2 germline mutation carriers. However, at the current time, there are insufficient data to provide evidence-based guidelines regarding the optimal timing or specific intervention to prevent cancers in these high-risk women.

Low Alcohol and Cigarette Use Is Associated to the Risk of Developing Chronic Pancreatitis.

PubMed

Di Leo, Milena; Leandro, Gioacchino; Singh, Satish K; Mariani, Alberto; Bianco, Margherita; Zuppardo, Raffaella Alessia; Goni, Elisabetta; Rogger, Teresa Marzia; Di Mario, Francesco; Guslandi, Mario; De Cobelli, Francesco; Del Maschio, Alessandro; Testoni, Pier Alberto; Cavestro, Giulia Martina

2017-02-01

The aim of this study was to investigate the contribution of smoking and alcohol intake and pancreas divisum on the risk of developing chronic pancreatitis (CP). Consecutive patients with CP who underwent secretin-enhanced magnetic resonance cholangiopancreatography were compared with consecutive patients without pancreatic disease who underwent secretin-enhanced magnetic resonance cholangiopancreatography for irritable bowel syndrome. We enrolled 145 consecutive CP patients and 103 irritable bowel syndrome patients from 2010 to 2014. In a univariate analysis, statistically significant differences in sex, mean age, and the duration and amount of cigarette and alcohol use were found. Per a receiver operating characteristic curve analysis, thresholds for cigarette and alcohol consumption were, respectively, 5.5 cigarettes and 13.5 g daily. In a multivariate analysis, independent risk factors for CP were male sex (odds ratio [OR], 2.05), smoking more than 5.5 cigarettes per day (OR, 2.72), and drinking more than 13.5 g/d (OR, 6.35). In an Italian population, we confirmed smoking and alcohol as cofactors in the development of CP. This study shows that alcohol intake and smoking habits are 2 of the most important risk factors for the development of CP.

Repeatability of measurements of removal of mite-infested brood to assess Varroa Sensitive Hygiene

USDA-ARS?s Scientific Manuscript database

Varroa Sensitive Hygiene is a useful resistance trait that bee breeders could increase in different populations with cost-effective and reliable tests. We investigated the reliability of a one-week test estimating the changes in infestation of brood introduced into highly selected and unselected co...

Selection signature analysis in Holstein cattle identified genes known to affect reproduction

USDA-ARS?s Scientific Manuscript database

Using direct comparison of 45,878 SNPs between a group of Holstein cattle unselected since 1964 and contemporary Holsteins that on average take 30 days longer for successful conception than the 1964 Holsteins, we conducted selection signature analyses to identify genomic regions associated with dair...

How Long Will I Be Blue? Prolonged Skin Staining Following Sentinel Lymph Node Biopsy Using Intradermal Patent Blue Dye

PubMed Central

Gumus, Metehan; Gumus, Hatice; Jones, Sue E; Jones, Peter A; Sever, Ali R; Weeks, Jennifer

2013-01-01

Summary Background Blue dye used for sentinel lymph node biopsy (SLNB) in breast cancer patients may cause prolonged skin discoloration at the site of injection. The aim of this study was to assess the duration of such skin discoloration. Patients and Methods 236 consecutive patients who had undergone breast conserving surgery and SLNB for breast cancer were reviewed prospectively from January 2007 to December 2009. Results Of the 236 patients, 2 had undergone bilateral surgery, and 41 had been examined in consecutive yearly reviews. Blue discoloration remained visible at the injection site after 12, 24, and > 36 months in 36.5, 23.6, and 8.6% of the patients, respectively. Conclusion The use of patent blue for identification of the sentinel lymph node in patients undergoing breast cancer surgery may result in prolonged discoloration of the skin at the injection site. PMID:24415970

Outcomes of Cardiopulmonary Resuscitation and Estimation of Healthcare Costs in Potential ‘Do Not Resuscitate’ Cases

PubMed Central

Ahmad, Akhwand S.; Mudasser, Sayed; Khan, Muhammad N.; Abdoun, Hafiz N. H.

2016-01-01

Objectives: Cardiopulmonary resuscitation (CPR) is a life-saving procedure which may fail if applied unselectively. ‘Do not resuscitate’ (DNR) policies can help avoid futile life-saving attempts among terminally-ill patients. This study aimed to assess CPR outcomes and estimate healthcare costs in potential DNR cases. Methods: This retrospective study was carried out between March and June 2014 and included 50 adult cardiac arrest patients who had undergone CPR at Sultan Qaboos Hospital in Salalah, Oman. Medical records were reviewed and treating teams were consulted to determine DNR eligibility. The outcomes, clinical risk categories and associated healthcare costs of the DNR candidates were assessed. Results: Two-thirds of the potential DNR candidates were ≥60 years old. Eight patients (16%) were in a vegetative state, 39 (78%) had an irreversible terminal illness and 43 (86%) had a low likelihood of successful CPR. Most patients (72%) met multiple criteria for DNR eligibility. According to clinical risk categories, these patients had terminal malignancies (30%), recent massive strokes (16%), end-stage organ failure (30%) or were bed-bound (50%). Initial CPR was unsuccessful in 30 patients (60%); the remaining 20 patients (40%) were initially resuscitated but subsequently died, with 70% dying within 24 hours. These patients were ventilated for an average of 5.6 days, with four patients (20%) requiring >15 days of ventilation. The average healthcare cost per patient was USD $1,958.9. Conclusion: With careful assessment, potential DNR patients can be identified and futile CPR efforts avoided. Institutional DNR policies may help to reduce healthcare costs and improve services. PMID:26909209

Choroidal metastasis in disseminated lung cancer: frequency and risk factors.

PubMed

Kreusel, Klaus-Martin; Wiegel, Thomas; Stange, Marit; Bornfeld, Norbert; Hinkelbein, Wolfgang; Foerster, Michael H

2002-09-01

To determine frequency, risk factors, and benefit of a prospective screening for intraocular metastasis in patients with metastatic lung cancer. Consecutive observational case series. An ophthalmologic screening was performed on 84 consecutive patients suffering from metastatic lung cancer. Medical history and disease stage were evaluated in regard to the risk for intraocular metastasis. In six patients (7.1%) choroidal metastasis (CM) was detected. Choroidal metastasis was present only when at least two other organ system were affected by metastasis (P =.03). The choroid was the sixth common site of organ metastasis. Mean remaining life span in patients with CM was 1.9 (0.2-5.9) months. Choroidal metastasis is common in advanced metastatic lung cancer. However, due to the short survival of affected individuals, a systematic screening of at-risk patients for CM seems to be of limited benefit.

Ophthalmologic screening in 25 consecutive geriatric psychiatric inpatient admissions.

PubMed

Billick, Stephen B; Garakani, Amir

2014-03-01

In the aging process, people are at increasing risk of visual abnormalities such as cataracts, glaucoma, age-related macular degeneration, and other retinal defects. This holds true for geriatric psychiatric patients as well. These ophthalmic problems may increase risk of falls or increase the comorbidity from dementing processes and depression. Geriatric patients presenting for psychiatric treatment may also be misdiagnosed or under-diagnosed as a result of these visual problems. This quality assurance review of 25 consecutive geriatric psychiatric inpatients demonstrated discrepancies between chart documentation and actual ophthalmologic pathology present in the patients. Doing a simple but complete ophthalmologic screening as part of the general physical examination on admission to an inpatient psychiatric unit can identify those patients who will need more in depth examination of their eyes and promote more accurate differential diagnoses for the patients.

Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area

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

Jimenez-Jimenez, F.J.; Mateo, D.; Gimenez-Roldan, S.

1992-01-01

Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex-matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p less than 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedatingmore » the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future case-control studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed.« less

Cerebellar damage impairs the self-rating of regret feeling in a gambling task

PubMed Central

Clausi, Silvia; Coricelli, Giorgio; Pisotta, Iolanda; Pavone, Enea Francesco; Lauriola, Marco; Molinari, Marco; Leggio, Maria

2015-01-01

Anatomical, clinical, and neuroimaging evidence implicates the cerebellum in processing emotions and feelings. Moreover recent studies showed a cerebellar involvement in pathologies such as autism, schizophrenia and alexithymia, in which emotional processing have been found altered. However, cerebellar function in the modulation of emotional responses remains debated. In this study, emotions that are involved directly in decision-making were examined in 15 patients (six males; age range 17–60 years) affected by cerebellar damage and 15 well matched healthy controls. We used a gambling task, in which subjects’ choices and evaluation of outcomes with regard to their anticipated and actual emotional impact were analyzed. Emotions, such as regret and relief, were elicited, based on the outcome of the unselected gamble. Interestingly, despite their ability to avoid regret in subsequent choices, patients affected by cerebellar lesions were significantly impaired in evaluating the feeling of regret subjectively. These results demonstrate that the cerebellum is involved in conscious recognizing of negative feelings caused by the sense of self-responsibility for an incorrect decision. PMID:25999829

Endoscopic sleeve gastroplasty: the learning curve.

PubMed

Hill, Christine; El Zein, Mohamad; Agnihotri, Abhishek; Dunlap, Margo; Chang, Angela; Agrawal, Alison; Barola, Sindhu; Ngamruengphong, Saowanee; Chen, Yen-I; Kalloo, Anthony N; Khashab, Mouen A; Kumbhari, Vivek

2017-09-01

 Endoscopic sleeve gastroplasty (ESG) is gaining traction as a minimally invasive bariatric treatment. Concern that the learning curve may be slow, even among those proficient in endoscopic suturing, is a barrier to widespread implementation of the procedure. Therefore, we aimed to define the learning curve for ESG in a single endoscopist experienced in endoscopic suturing who participated in a 1-day ESG training program.  Consecutive patients who underwent ESG between February 2016 and November 2016 were included. The performing endoscopist, who is proficient in endoscopic suturing for non-ESG procedures, participated in a 1-day ESG training session before offering ESG to patients. The outcome measurements were length of procedure (LOP) and number of plications per procedure. Nonlinear regression was used to determine the learning plateau and calculate the learning rate.  Twenty-one consecutive patients (8 males), with mean age 47.7 ± 11.2 years and mean body mass index 41.8 ± 8.5 kg/m 2 underwent ESG. LOP decreased significantly across consecutive procedures, with a learning plateau at 101.5 minutes and a learning rate of 7 cases ( P  = 0.04). The number of plications per procedure also decreased significantly across consecutive procedures, with a plateau at 8 sutures and a learning rate of 9 cases ( P  < 0.001). Further, the average time per plication decreased significantly with consecutive procedures, reaching a plateau at 9 procedures ( P  < 0.001).  Endoscopists experienced in endoscopic suturing are expected to achieve a reduction in LOP and number of plications per procedure in successive cases, with progress plateauing at 7 and 9 cases, respectively.

Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia.

PubMed

Lazarevic, Vladimir; Hörstedt, Ann-Sofi; Johansson, Bertil; Antunovic, Petar; Billström, Rolf; Derolf, Åsa; Lehmann, Sören; Möllgård, Lars; Peterson, Stefan; Stockelberg, Dick; Uggla, Bertil; Vennström, Lovisa; Wahlin, Anders; Höglund, Martin; Juliusson, Gunnar

2015-05-01

Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression.

PubMed

Dicker, Frank; Schnittger, Susanne; Haferlach, Torsten; Kern, Wolfgang; Schoch, Claudia

2006-11-01

Compared with fluorescence in situ hybridization (FISH), conventional metaphase cytogenetics play only a minor prognostic role in chronic lymphocytic leukemia (CLL) so far, due to technical problems resulting from limited proliferation of CLL cells in vitro. Here, we present a simple method for in vitro stimulation of CLL cells that overcomes this limitation. In our unselected patient population, 125 of 132 cases could be successfully stimulated for metaphase generation by culture with the immunostimulatory CpG-oligonucleotide DSP30 plus interleukin 2. Of 125 cases, 101 showed chromosomal aberrations. The aberration rate is comparable to the rate detected by parallel interphase FISH. In 47 patients, conventional cytogenetics detected additional aberrations not detected by FISH analysis. A complex aberrant karyotype, defined as one having at least 3 aberrations, was detected in 30 of 125 patients, compared with only one such case as defined by FISH. Conventional cytogenetics frequently detected balanced and unbalanced translocations. A significant correlation of the poor-prognosis unmutated IgV(H) status with unbalanced translocations and of the likewise poor-prognosis CD38 expression to balanced translocations and complex aberrant karyotype was found. We demonstrate that FISH analysis underestimates the complexity of chromosomal aberrations in CLL. Therefore, conventional cytogenetics may define subgroups of patients with high risk of progression.

Clinical Outcomes from Unselected "Real-World" Patients with Long Coronary Lesion Receiving 40 mm Biodegradable Polymer Coated Sirolimus-Eluting Stent.

PubMed

Polavarapu, Anurag; Polavarapu, Raghava Sarma; Prajapati, Jayesh; Thakkar, Kamlesh; Raheem, Asif; Mayall, Tamanpreet; Thakkar, Ashok

2015-01-01

Background. Long lesions being implanted with drug-eluting stents (DES) are associated with relatively high restenosis rates and higher incidences of adverse events. Objectives. We aimed to examine the safety and efficacy of the long (40 mm) biodegradable polymer coated Indolimus sirolimus-eluting stent (SES) in real-world patients with long coronary lesions. Methods. This study was observational, nonrandomized, retrospective, and carried out in real-world patients. A total of 258 patients were enrolled for the treatment of long coronary lesions, with 40 mm Indolimus. The primary endpoints in the study were incidence of major adverse cardiac events (MACE), a miscellany of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) or target vessel revascularization (TVR), and stent thrombosis (ST) up to 6-month follow-up. Results. The study population included higher proportion of males (74.4%) and average age was 53.2 ± 11.0 years. A total of 278 lesions were intervened successfully with 280 stents. The observed MACE at 6-month follow-up was 2.0%, which included 0.8% cardiac death and 1.2% MI. There were no TLR or TVR and ST observed during 6-month follow-up. Conclusions. The long (40 mm) Indolimus stent demonstrated low MACE rate and was proven to be safe and effective treatment for long lesions in "real-world" patients.

Outcome of physiotherapy as part of a multidisciplinary rehabilitation in an unselected polio population with one-year follow-up: an uncontrolled study.

PubMed

Bertelsen, Merete; Broberg, Susse; Madsen, Ellen

2009-01-01

The aim of this study was to evaluate the outcome of physiotherapy as part of a multidisciplinary rehabilitation. Prospective uncontrolled intervention study. Fifty patients with late effects of polio, first time referred to physiotherapy at the Danish Society of Polio and Accident Victims (PTU) Rehabilitation Centre. The intervention was physiotherapy as an essential part of an individually planned multidisciplinary rehabilitation. The outcome measures Six-Minute Walk Test and Timed-Stands Test were used to assess the functional capacity. Quality of life was evaluated by Medical Outcome Survey Short Form (SF-36) and fatigue by Multidimensional Fatigue Inventory (MFI-20). Patients were tested at baseline; 3 months after the start of rehabilitation and at one-year follow-up. The patients showed significantly better functional capacity on all measurements 3 months after start of intervention and at one-year follow-up. The patients showed significant improvement in 3 of the SF-36 dimensions regarding quality of life, but only the improvement in "general health" remained after one year. This study shows that patients with late effects of polio, who experience new problems related to polio, can benefit from an individually planned multidisciplinary intervention with emphasis on physiotherapy, and the improvement in physical capacity and general health can remain at one-year follow-up.

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

PubMed

Osman, Faizel; Franklyn, Jayne A; Daykin, Jacqueline; Chowdhary, Saqib; Holder, Roger L; Sheppard, Michael C; Gammage, Michael D

2004-08-15

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Recurrent pregnancy loss: what is the impact of consecutive versus non-consecutive losses?

PubMed

Egerup, P; Kolte, A M; Larsen, E C; Krog, M; Nielsen, H S; Christiansen, O B

2016-11-01

Is there a different prognostic impact for consecutive and non-consecutive early pregnancy losses in women with secondary recurrent pregnancy loss (RPL)? Only consecutive early pregnancy losses after the last birth have a statistically significant negative prognostic impact in women with secondary RPL. The risk of a new pregnancy loss increases with the number of previous pregnancy losses in patients with RPL. Second trimester losses seem to exhibit a stronger negative impact than early losses. It is unknown whether the sequence of pregnancy losses plays a role for the prognosis in patients with a prior birth. This retrospective cohort study of pregnancy outcome in patients with unexplained secondary RPL included in three previously published, Danish double-blinded placebo-controlled trials of intravenous immunoglobulin (IvIg) conducted from 1991 to 2014. No other treatments were given. Patients with documented explained pregnancy losses (ectopic pregnancies and aneuploid miscarriages) were excluded. Of the 168 patients included in the trials, 127 had secondary RPL and experienced a subsequent live birth or unexplained pregnancy loss in the first pregnancy after giving informed consent to participate in the trials (the index pregnancy). Data analyzed by multivariate analysis included the independent variables age, the number of early pregnancy losses before and after the last birth, respectively and a second trimester pregnancy loss before or after the last birth, respectively. The outcome variable was unexplained loss in the index pregnancy. In patients with secondary RPL, both a late and each early loss before the last birth did not significantly influence the risk of a new pregnancy loss in the index pregnancy: incidence rate ratio (IRR) 1.31 (95% CI 0.62-2.77) and IRR 0.88 (95% CI 0.70-1.11), respectively. In contrast, the impact on risk of pregnancy loss conferred by a late and by each early pregnancy loss occurring after the birth was significant: IRR 2.15 (95% CI 1.57-2.94, P < 0.0001) and IRR 1.14 (95% CI 1.04-1.24, P = 0.002), respectively. Of the patients, 48% were treated with IvIg, which could influence the results. However, allocation to IvIg was random and prognostic variables were equally distributed in IvIg and placebo-treated patients. A birth in women with secondary RPL eradicates the negative prognostic impact of previous pregnancy losses and this finding is important for our understanding of the pathogenesis. It indicates that only consecutive pregnancy losses should count in the definition of RPL. There was no particular funding for this study. The authors declare that there is no conflict of interest. Not applicable for two of the included randomized controlled trials. For the last trial: Clinical.Gov NCT00722475. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adult-onset intradural spinal teratoma: report of 18 consecutive cases and outcomes in a single center.

PubMed

Wan, Wei; Yang, Cheng; Yan, Wangjun; Liu, Tielong; Yang, Xinghai; Song, Dianwen; Xiao, Jianru

2017-07-01

Eighteen consecutive patients with adult-onset intradural spinal teratoma underwent surgical treatment in our center from 1998 to 2013. Teratoma is defined as a neoplasm composed of elements derived from three germ cell layers (ectoderm, endoderm and mesoderm). Intraspinal teratoma is extremely rare and accounts for 0.2-0.5% of all spinal cord tumors. Moreover, teratoma occurs primarily in neonates and young children. Adult-onset intradural spinal teratoma is even rare. The aim of this study was to discuss the clinical characteristics, diagnosis and therapeutic strategies of adult-onset intradural spinal teratoma. This retrospective study included 18 consecutive adult patients with intradural teratoma who were surgically treated in our center between 1998 and 2013. The clinical features, pathogenesis, diagnostic strategies and surgical outcomes were discussed. Neurological function outcomes were evaluated by the JOA scoring system. Of the 18 included patients, 4 patients received subtotal resection and the other 14 patients received total resection. All the 18 cases were diagnosed with mature teratoma. The mean follow-up period was 79.7 (median 60.5; range 27-208) months. Local recurrence occurred in two of the four patients who underwent subtotal resection and in no patient who underwent total resection. The neurologic status improved in 16 cases and remained unchanged in the other two patients. Adult-onset intradural spinal teratoma is extremely rare. To the best of our knowledge, this is the largest series of patients with this disease. Despite the slow-growth and indolent nature, radical resection remains the recommended treatment to reduce tumor recurrence.

Fluoroscopically Guided Transcervical Fallopian Tube Recanalization of Post-Sterilization Reversal Mid-Tubal Obstructions

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

Houston, J. Graeme; Anderson, David; Mills, John

2000-03-15

Purpose: To assess the technical success and early outcome of fluoroscopically guided transcervical fallopian tube recanalization (FTR) in mid-tubal occlusion following sterilization reversal surgery.Methods: From July 1995 to January 1998, patients with greater than 12 months secondary infertility underwent hysterosalpingography (HSG). FTR was performed in proximal or mid-tubal occlusion. Cases of FTR in mid-tubal occlusion were included in this study. Technical success (defined as complete tubal patency) using a standard guidewire and hydrophilic glidewire, the number of patients with at least one patent tube, and the intrauterine and ectopic pregnancy rates were determined.Results: Twenty-six infertile patients with previous sterilization reversalmore » underwent HSG. Eight of 26 (31%) patients (mean age 32 years, range 23-37 years), had attempted FTR for mid-tubal occlusion at the site of surgical anastomosis. Fourteen tubes were attempted as there were two previous salpingectomies. Technical success was achieved in eight of 14 (57%) tubes attempted, resulting in five of eight (62%) patients having at least one patent tube. At follow-up (mean 18 months, range 12-28 months) in these five patients there was one intrauterine pregnancy. There were no ectopic pregnancies.Conclusions: FTR in mid-tubal obstruction in infertile patients following sterilization reversal surgery is technically feasible and may result in intrauterine pregnancy. In this small group there was a lower technical success rate and lower pregnancy rate than in unselected proximal tubal occlusion.« less

Higher serum chloride concentrations are associated with acute kidney injury in unselected critically ill patients.

PubMed

Zhang, Zhongheng; Xu, Xiao; Fan, Haozhe; Li, Danyu; Deng, Hongsheng

2013-10-28

Chloride administration has been found to be harmful to the kidney in critically ill patients. However the association between plasma chloride concentration and renal function has never been investigated. This was a retrospective study conducted in a tertiary 24-bed intensive care unit from September 2010 to November 2012. Data on serum chloride for each patient during their ICU stay were abstracted from electronic database. Cl0 referred to the initial chloride on ICU entry, Cl(max), Cl(min) and Cl(mean) referred to the maximum, minimum and mean chloride values before the onset of AKI, respectively. AKI was defined according to the conventional AKIN criteria. Univariate and multivariable analysis were performed to examine the association of chloride and AKI development. A total of 1221 patients were included into analysis during study period. Three hundred and fifty-seven patients (29.2%) developed AKI. Cl(max) was significantly higher in AKI than in non-AKI group (111.8 ± 8.1 vs 107.9 ± 5.4 mmol/l; p < 0.001); Cl0 was not significantly different between AKI and non-AKI patients; Cl(mean) was significantly higher in AKI than non-AKI (104.3 ± 5.8 vs 103.4 ± 4.5;  = 0.0047) patients. Cl(max) remained to be associated with AKI in multivariable analysis (OR: 1.10, 95% CI: 1.08-1.13). Chloride overload as represented by Cl(mean) and Cl(max) is significantly associated with the development of AKI.

TEL/AML1 positivity in childhood ALL: average or better prognosis? Czech Paediatric Haematology Working Group.

PubMed

Zuna, J; Hrusák, O; Kalinová, M; Muzíková, K; Starý, J; Trka, J

1999-01-01

The presence of TEL/AML1 fusion gene in childhood acute lymphoblastic leukaemia (ALL) defines a subgroup of patients with better than average outcome. However, the prognostic significance of this aberration has recently been disputed by the Berlin-Frankfurt-Münster (BFM) study group due to its relatively high incidence found in relapsed patients (19.6% and 21.9%, in two cohorts). In contrast, only four out of 45 (8.9%) unselected relapsed patients (all of whom had been treated according to BFM protocols) in the Czech Republic carry this fusion. From March 1995 to June 1998, 41 out of 190 (21.6%) newly diagnosed children with ALL were TEL/AML1-positive. There is a statistically significant difference between the incidence of TEL/AML1 fusion at diagnosis and at relapse within our group (P = 0.035). Interim analysis of the minimal residual disease (MRD) detection shows heterogeneity within the group of newly diagnosed TEL/AML1-positive leukaemias--10 out of 24 patients tested at the end of induction therapy had detectable levels of MRD. However, only one of these patients reached relapse-predictive level (10(-3)) of MRD. In conclusion, we corroborate low frequency of TEL/AML1 positivity among relapsed patients with ALL among Czech children who are treated by the BFM protocols. Moreover, we demonstrate different patterns of bone marrow clean-up in TEL/AML1-positive patients.

Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis.

PubMed

Takeda, Takashi; Banno, Kouji; Yanokura, Megumi; Adachi, Masataka; Iijima, Moito; Kunitomi, Haruko; Nakamura, Kanako; Iida, Miho; Nogami, Yuya; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

2016-10-14

Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 ( MLH1 ) and MutS homolog 2 ( MSH2 ) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1 , MSH2 , and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6 . The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

[Sequelae of severe craniocerebral injuries. An epidemiological study in the Canton of St. Gallen].

PubMed

Annoni, J M; Beer, S; Kesselring, J

1991-02-16

Severe head injuries often lead to serious medical and socioeconomic sequelae. The incidence rate indicated in other studies shows a wide variation due to differences in selection criteria. Based upon an unselected population, the incidence of severe head injury was calculated and the surviving patients were interviewed and clinically examined 3 years after the accident in order to describe the course, rehabilitation and psychosocial sequelae after severe head injury. Retrospectively we collected 80 patients living in the canton of St. Gallen who had a severe head injury requiring hospitalization in 1987, indicating an incidence of 20 per 100,000 inhabitants. 22 (28%) of these patients died as a consequence of the head trauma. The best predictor was the Glasgow coma score at admission, which showed a highly significant direct correlation with survival rate. Regarding the degree of impairment of survivors the duration of posttraumatic amnesia was the best predictive parameter. Of the 45 patients controlled 3 years after the head trauma only 11% were severely impaired in daily activities. 79% of the patients who were gainfully employed before the accident were working full- or at least part-time. However, only 3 patients (7%) were absolutely free of symptoms. Most patients suffered from cognitive and emotional deficits. Based on an estimated incidence for minor head trauma of 174 per 100,000 inhabitants, a total annual incidence for all head traumas of 194 per 100,000 inhabitants is calculated, with severe head injury representing about 1/9 of all head injuries.

Characterization of radiographic features of consecutive lumbar spondylolisthesis.

PubMed

Sun, Yapeng; Wang, Hui; Yang, Dalong; Zhang, Nan; Yang, Sidong; Zhang, Wei; Ding, Wenyuan

2016-11-01

Radiographic features of consecutive lumbar spondylolisthesis were retrospectively analyzed in a total of 17 patients treated for this condition at the Third Hospital of Hebei Medical University from June 2005 to March 2012.To investigate the radiographic features, pelvic compensatory mechanisms, and possible underlying etiologies of consecutive lumbar spondylolisthesis.To the best of our knowledge, there is no previous report concerning the characteristics of consecutive lumbar spondylolisthesis.The Taillard index and the lumbar lordosis (LL), pelvic incidence (PI), sacrum slope (SS), and pelvic tilt (PT) were determined on lateral X-ray images, and the angular displacement was analyzed on flexion-extension X-ray images. Correlation between LL and various pelvic parameters and correlation between Taillard index and angular displacement were assessed by Pearson correlation analysis.A total of 20 cases of isthmic spondylolisthesis and 14 of degenerative spondylolisthesis were retrospectively studied in 17 patients. The Taillard index and the angular displacement in the lower vertebrae were both larger than those in the upper vertebrae. Statistical analysis revealed that LL was correlated with PI and PT, whereas PI was correlated with PT and SS. However, no correlation was identified between Taillard index and angular displacement.In consecutive lumbar spondylolisthesis, the degree of vertebral slip and the angular displacement of the lower vertebrae were both greater than those of the upper vertebrae, indicating that the compensatory mechanism of the pelvis plays an important role in maintaining sagittal balance.

Characterization of radiographic features of consecutive lumbar spondylolisthesis

PubMed Central

Sun, Yapeng; Wang, Hui; Yang, Dalong; Zhang, Nan; Yang, Sidong; Zhang, Wei; Ding, Wenyuan

2016-01-01

Abstract Radiographic features of consecutive lumbar spondylolisthesis were retrospectively analyzed in a total of 17 patients treated for this condition at the Third Hospital of Hebei Medical University from June 2005 to March 2012. To investigate the radiographic features, pelvic compensatory mechanisms, and possible underlying etiologies of consecutive lumbar spondylolisthesis. To the best of our knowledge, there is no previous report concerning the characteristics of consecutive lumbar spondylolisthesis. The Taillard index and the lumbar lordosis (LL), pelvic incidence (PI), sacrum slope (SS), and pelvic tilt (PT) were determined on lateral X-ray images, and the angular displacement was analyzed on flexion–extension X-ray images. Correlation between LL and various pelvic parameters and correlation between Taillard index and angular displacement were assessed by Pearson correlation analysis. A total of 20 cases of isthmic spondylolisthesis and 14 of degenerative spondylolisthesis were retrospectively studied in 17 patients. The Taillard index and the angular displacement in the lower vertebrae were both larger than those in the upper vertebrae. Statistical analysis revealed that LL was correlated with PI and PT, whereas PI was correlated with PT and SS. However, no correlation was identified between Taillard index and angular displacement. In consecutive lumbar spondylolisthesis, the degree of vertebral slip and the angular displacement of the lower vertebrae were both greater than those of the upper vertebrae, indicating that the compensatory mechanism of the pelvis plays an important role in maintaining sagittal balance. PMID:27861359

[Monitoring AIDS patients for the development of cytomegalovirus (CMV) disease using multiplex PCR].

PubMed

Terra, A P; Silva-Vergara, M L; Gomes, R A; Pereira, C L; Simpson, A J; Caballero, O L

2000-01-01

The human cytomegalovirus is an important pathogen in patients infected with the human immunodeficiency virus (HIV). The CMV viral load seems to be predictor of the development of the CMV disease in these patients. We used a multiplex PCR protocol that also provides quantitative information in those samples from which a single band is amplified and contains fewer viral genomes than those from which both targets are amplified. Monthly blood samples were collected from 270 AIDS patients. From twenty patients, two CMV targets were amplified three or more consecutive times and these patients developed CMV related disease during the study. In contrast, patients who did not result positive for both viral targets, for three or more consecutive times, or who had alternating positive and negative samples during the follow up did not present CMV related disease. The results suggest that the PCR multiplex can be used for the identification of HIV positive patients with higher risk of development of CMV disease.

Suitability of Varicose Veins for Endovenous Treatments

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

Goode, S. D., E-mail: s.goode@sheffield.ac.u; Kuhan, G.; Altaf, N.

2009-09-15

The aim of the study was to assess the suitability of radiofrequency ablation (RFA), endovenous laser ablation (EVLA), and foam sclerotherapy (FS) for patients with symptomatic varicose veins (VVs). The study comprised 403 consecutive patients with symptomatic VVs. Data on 577 legs from 403 consecutive patients with symptomatic VVs were collected for the year 2006. Median patient age was 55 years (interquartile range 45-66), and 62% patients were women. A set of criteria based on duplex ultrasonography was used to select patients for each procedure. Great saphenous vein (GSV) reflux was present in 77% (446 of 577) of legs. Overall,more » 328 (73%) of the legs were suitable for at least one of the endovenous options. Of the 114 legs with recurrent GSV reflux disease, 83 (73%) were suitable to receive endovenous therapy. Patients with increasing age were less likely to be suitable for endovenous therapy (P = 0.03). Seventy-three percent of patients with VVs caused by GSV incompetence are suitable for endovenous therapy.« less

Health Care Utilization and Expenditures Associated With Remote Monitoring in Patients With Implantable Cardiac Devices.

PubMed

Ladapo, Joseph A; Turakhia, Mintu P; Ryan, Michael P; Mollenkopf, Sarah A; Reynolds, Matthew R

2016-05-01

Several randomized trials and decision analysis models have found that remote monitoring may reduce health care utilization and expenditures in patients with cardiac implantable electronic devices (CIEDs), compared with in-office monitoring. However, little is known about the generalizability of these findings to unselected populations in clinical practice. To compare health care utilization and expenditures associated with remote monitoring and in-office monitoring in patients with CIEDs, we used Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases. We selected patients newly implanted with an implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy defibrillator (CRT-D), or permanent pacemaker (PPM), in 2009, who had continuous health plan enrollment 2 years after implantation. Generalized linear models and propensity score matching were used to adjust for confounders and estimate differences in health care utilization and expenditures in patients with remote or in-office monitoring. We identified 1,127; 427; and 1,295 pairs of patients with a similar propensity for receiving an ICD, CRT-D, or PPM, respectively. Remotely monitored patients with ICDs experienced fewer emergency department visits resulting in discharge (p = 0.050). Remote monitoring was associated with lower health care expenditures in office visits among patients with PPMs (p = 0.025) and CRT-Ds (p = 0.006) and lower total inpatient and outpatient expenditures in patients with ICDs (p <0.0001). In conclusion, remote monitoring of patients with CIEDs may be associated with reductions in health care utilization and expenditures compared with exclusive in-office care. Copyright © 2016 Elsevier Inc. All rights reserved.

[Ambulatory laparoscopic cholecystectomy. A cohort study of 1,600 consecutive cases].

PubMed

Planells Roig, Manuel; Garcia Espinosa, Rafael; Cervera Delgado, María; Navarro Vicente, Francisco; Carrau Giner, Miguel; Sanahuja Santafé, Angel; Arnal Bertomeu, Consuelo

2013-03-01

A descriptive analysis of day-case laparoscopic cholecystectomy (ALC) in a cohort of 1,600 consecutive patients performed in Instituto de Cirugía y Aparato Digestivo (ICAD), Clínica Quirón de Valencia in the period 1997-2010. Prospective observational study of 1,601 consecutive patients undergoing elective laparoscopic cholecystectomy (LC) provided by the regional health service and private health companies. Conversion rate, non-planned admissions, readmissions, surgery duration and demographics. ALC was successfully performed in 80.8% of cases. LC with over-night (ON) stay accounted for 13.4% of patients. Admission was necessary in 4.6%. Mortality was 0.13%, 0.08 in ALC and 0.5% in ON LC. Readmissions occurred in 2.1%, 1.6% in ALC group, 5.4% in ON stay and 4.2% in admission group. ALC is a reliable and safe procedure. Minimization of admission rates is the key for cost-effective optimization in the management of cholelithiasis. ALC should be considered as the reference standard in gallbladder stone disease treatment. Copyright © 2011 AEC. Published by Elsevier Espana. All rights reserved.

Genetic counseling for beta-thalassemia trait following health screening in a health maintenance organization: comparison of programmed and conventional counseling.

PubMed Central

Fisher, L; Rowley, P T; Lipkin, M

1981-01-01

Providing adequate counseling of patients identified in genetic screening programs is a major responsibility and expense. Adults in a health maintenance organization, unselected for interest, were screened for beta-thalassemia trait as part of preventive health care. Counseling was provided by either a trained physician (conventional counseling) or by a videotape containing the same information followed by an opportunity to question a trained physician (programmed counseling). Immediately before and after counseling, knowledge of thalassemia, knowledge of genetics, and mood change were assessed by questionnaire. Comparable mood changes and similar learning about thalassemia and genetics occurred with both counseling methods. Thus, as judged by immediate effects on knowledge and mood, videotaped instruction can greatly reduce professional time required for genetic counseling and facilitate the incorporation of genetic screening into primary health care. PMID:7325162

Protocol for a randomized comparison of integrated versus consecutive dual task practice in Parkinson’s disease: the DUALITY trial

PubMed Central

2014-01-01

Background Multiple tasking is an integral part of daily mobility. Patients with Parkinson’s disease have dual tasking difficulties due to their combined motor and cognitive deficits. Two contrasting physiotherapy interventions have been proposed to alleviate dual tasking difficulties: either to discourage simultaneous execution of dual tasks (consecutive training); or to practice their concurrent use (integrated training). It is currently unclear which of these training methods should be adopted to achieve safe and consolidated dual task performance in daily life. Therefore, the proposed randomized controlled trial will compare the effects of integrated versus consecutive training of dual tasking (tested by combining walking with cognitive exercises). Methods and design Hundred and twenty patients with Parkinson’s disease will be recruited to participate in this multi-centered, single blind, randomized controlled trial. Patients in Hoehn & Yahr stage II-III, with or without freezing of gait, and who report dual task difficulties will be included. All patients will undergo a six-week control period without intervention after which they will be randomized to integrated or consecutive task practice. Training will consist of standardized walking and cognitive exercises delivered at home four times a week during six weeks. Treatment is guided by a physiotherapist twice a week and consists of two sessions of self-practice using an MP3 player. Blinded testers will assess patients before and after the control period, after the intervention period and after a 12-week follow-up period. The primary outcome measure is dual task gait velocity, i.e. walking combined with a novel untrained cognitive task to evaluate the consolidation of learning. Secondary outcomes include several single and dual task gait and cognitive measures, functional outcomes and a quality of life scale. Falling will be recorded as a possible adverse event using a weekly phone call for the entire study period. Discussion This randomized study will evaluate the effectiveness and safety of integrated versus consecutive task training in patients with Parkinson’s disease. The study will also highlight whether dual task gait training leads to robust motor learning effects, and whether these can be retained and carried-over to untrained dual tasks and functional mobility. Trial registration Clinicaltrials.gov NCT01375413. PMID:24674594

Some aspects of the DSM-III personality disorders illustrated by a consecutive sample of hospitalized patients.

PubMed

Dahl, A A

1986-01-01

The main innovations of DSM-III concerning the personality disorders are the assignment of a separate axis and definitions of diagnostic criteria for these disorders. Even with these improvements, diagnosis of the personality disorders shows only moderate interrater reliability. Reasons for this are discussed. Data from a consecutive sample of hospitalized patients are used to illustrate the prevalence of the personality disorders, the coexistence of axis I disorders, and the overlap within the personality disorders. The method of conditional probabilities is presented as a way to get better separation of these disorders.

My First 100 Consecutive Microvascular Free Flaps: Pearls and Lessons Learned in First Year of Practice

PubMed Central

2013-01-01

Background: Microvascular reconstruction for oncologic defects is a challenging and rewarding endeavor, and successful outcomes are dependent on a multitude of factors. This study represents lessons learned from a personal prospective experience with 100 consecutive free flaps. Methods: All patients’ medical records were reviewed for demographics, operative notes, and complications. Results: Overall 100 flaps were performed in 84 consecutive patients for reconstruction of breast, head and neck, trunk, and extremity defects. Nineteen patients underwent free flap breast reconstruction with 10 patients undergoing bilateral reconstruction and 2 patients receiving a bipedicle flap for reconstruction of a unilateral breast defect. Sixty-five free flaps were performed in 61 patients with 3 patients receiving 2 free flaps for reconstruction of extensive head and neck defects and 1 patient who required a second flap for partial flap loss. Trunk and extremity reconstruction was less common with 2 free flaps performed in each group. Overall, 19 patients (22.6%) developed complications and 14 required a return to the operating room. There were no flap losses in this cohort. Thorough preoperative evaluation and workup, meticulous surgical technique and intraoperative planning, and diligent postoperative monitoring and prompt intervention are critical for flap success. Conclusions: As a young plastic surgeon embarking in reconstructive plastic surgery at an academic institution, the challenges and dilemmas presented in the first year of practice have been daunting but also represent opportunities for learning and improvement. Skills and knowledge acquired from time, experience, and mentors are invaluable in optimizing outcomes in microvascular free flap reconstruction. PMID:25289221

Altered plasma levels of cytokines, soluble adhesion molecules and matrix metalloproteases in venous thrombosis.

PubMed

Mosevoll, Knut Anders; Lindås, Roald; Tvedt, Tor Henrik Anderson; Bruserud, Øystein; Reikvam, Håkon

2015-07-01

Recent studies have emphasized the importance of the inflammatory response mediated by monocyte and neutrophil activation in deep venous thrombosis (DVT); we therefore investigated whether this response was reflected in the plasma profile of inflammatory mediators in patients with suspected DVT. We included a group of 169 consecutive patients admitted to hospital from the primary health care service with suspected lower limb DVT. Plasma levels of 43 mediators were examined for a cohort of 89 consecutive patients and 20 healthy controls by Luminex multiplex analyses, i.e. 13 interleukins, 3 immunomodulatory cytokines, 8 chemokines, 8 growth factors, 3 adhesion molecules and 8 matrix metalloproteases. Selected mediators were analyzed for a second cohort of 80 consecutive patients. Thirty-five of 169 (21%) of referred patients were diagnosed with DVT. Only P-selectin (p<0.0001), vascular cell adhesion protein 1 (VCAM-1, p=0.0009), matrix metalloprotease 8 (MMP-8, p=0.0151) and hepatocyte growth factor (HGF, p=0.0415) differed significantly when comparing patients with and without DVT. When comparing DVT patients with healthy controls we observed significant differences for several mediators, where P-selectin (p=0.0009), VCAM-1 (p<0.0001), all the MMPs (all p<0.0014) and HGF (p<0.0001) showed the strongest significant differences. Unsupervised hierarchical clustering analyses based on biomarkers showing differences between patients with and without DVT could be used to identify patient subsets that differed significantly in DVT frequency. Plasma biomarker profiling of selected soluble mediators can be used to identify subsets among patients with suspected lower limb thrombosis that differ significantly in their frequencies of DVT. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients.

PubMed

Chan, Jessie Ying Wing; Che, Kit I; Lam, Karry Mau Chu; Chow, Kai-Ming; Chung, Kwok-Yi; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

2007-04-01

Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial. We studied 165 unselected adult PD patients. We compared the comprehensive Malnutrition-Inflammation Score (MIS) and the 7-point Subjective Global Assessment (SGA) score. The mean age was 59.2 +/- 11.5 years. Seventy patients were male. MIS significantly correlated with the SGA score (r =-0.667, P < 0.001). Of the 165 patients, 132 (80.0%) had similar classification of nutritional status by SGA and MIS (Group I); 17 (10.3%) were classified as normal by SGA but moderately malnourished by MIS (Group II), while 16 (9.7%) were classified as normal by MIS but moderately malnourished by SGA (Group III). Group II had been dialysed longer than Group I (71.7 +/- 50.3 vs 40.7 +/- 37.5 months, P = 0.011). As compared with Group I, Group III was more likely to require helper for PD exchange (37.5%vs 9.7%, P = 0.004), marginally more likely to be diabetic (62.5%vs 35.6%, P = 0.085) and had a slightly higher Charlson's comorbidity score (6.13 +/- 1.78 vs 4.98 +/- 2.1, P = 0.085), although the latter two were not statistically significant. MIS has a reasonable correlation with the conventional SGA score in PD patients. Patients with limited self-care capability, diabetes and multiple comorbidities probably had worse score (i.e. worse nutrition) revealed by SGA than by MIS, while patients who had been dialysed longer had worse score revealed by MIS than by SGA.