Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer

Background and Aims: Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population. Methods: Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95 confidence intervals (CIs). Results: After adjustment for potential confounders, opium use (OR 1.91; 95 CI 1.06-3.43) and alcohol consumption (OR 4.16; 95 CI 1.86-9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95 CI 0.62-1.39). Conclusion: In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not. Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved

Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The CCTRN SENECA Trial.

BACKGROUND: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment. OBJECTIVES: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC. METHODS: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 10 RESULTS: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group. CONCLUSIONS: In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC

Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients

Background: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment. Objectives: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC. Methods: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 108 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers. Results: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group. Conclusions: In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC

A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial

Aims: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy. Methods and results: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups. Conclusions: This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients

Nonalcoholic fatty liver: The association with metabolic abnormalities, body mass index and central obesity - A population-based study

Background: To assess the prevalence of nonalcoholic fatty liver (NAFL) in Iran and to evaluate correlates of NAFL in categories of body mass index (BMI). Methods: Using a cluster random sampling approach, 7723 subjects over 18 years of age underwent abdominal ultrasonography, laboratory evaluations, blood pressure, and anthropometric measurements and were interviewed to obtain baseline characteristics. Prevalence of NAFL according to BMI and waist to hip ratio and its association with metabolic abnormalities in categories of BMI were assessed in multivariate analysis. Results: The overall prevalence of NAFL was 35.2 95% confidence interval (CI) 34.1-36.3. A significant number of subjects with BMI <30 had NAFL 22.1% (CI 21.0-23.2). Waist to hip ratio for 38.2% (CI 35.6-40.8) of the subjects with NAFL, and BMI <30 was higher than normal values. The odds ratio for association of NAFL and dyslipidemias were higher in subjects with BMI <30 versus those with BMI �30: (1) hypertriglyceridemia: 2.21 vs. 1.57, P=0.006; (2) lower high-density lipoprotein: 1.29 versus 0.98, P=0.046. Higher low-density lipoprotein also revealed greater association with NAFL in subjects with BMI <25 than those with BMI �25 (odds ratio 1.84 vs. 1.1, P=0.015). Conclusions: NAFL shows stronger association with central obesity compared to high BMI. NAFL has stronger association with dyslipidemias in subjects with low compared with high BMI. © Mary Ann Liebert, Inc. 2015

Immune responses to hepatitis B immunization 10–18 years after primary vaccination: a population-based cohort study

We evaluated the immune response to neonatal HBV immunization in children of infected parents 10–18 years after primary vaccination. Healthy individuals immunized with an infantile course of three doses of HBV vaccine were tested for persistence of anti-HB surface antibody (HBsAb). Those with an HBsAb level of <10 IU/mL received a booster dose of the vaccine with subsequent doses to those without protective titres. HBsAb concentrations were determined 4 weeks after each dose of the booster vaccine. The data were analysed separately for three age groups: 10–11, 12–14 and 15–18 years old. A total of 541 healthy individuals were studied. The highest seroprotection rate of 48% was observed in the youngest vaccinees (10–11 years old). This declined to 26.5% in the oldest (15–18 years old) group (P = 0.008). The youngest vaccinees showed the highest rate of anamnestic immune responses (96%). However, 25% of oldest individuals failed to mount an anamnestic immune response in challenge with a booster dose of the vaccine (P = 0.005), suggesting waning immunity with increasing age. Age (OR: 0.80; P = 0.01) and prebooster HBsAb levels (OR: 0.37; P = 0.01) identified responders to first booster doses of the vaccine by logistic regression analysis. The majority of high-risk vaccinees showed anamnestic immune response 10–11 years after primary immunization. However, we found a significant proportion (25%) of older individuals with no anamnetic response, which suggests a waning of immune memory. Detailed long-term follow-up studies are necessary to determine the risk of natural infection among these individuals before a booster schedule can be recommended. © 2016 John Wiley & Sons Lt

Ischemia and No Obstructive Stenosis (INOCA) at CT Angiography, CT Myocardial Perfusion, Invasive Coronary Angiography, and SPECT: The CORE320 Study

Background: CT allows evaluation of atherosclerosis, coronary stenosis, and myocardial ischemia. Data on the characterization of ischemia and no obstructive stenosis (INOCA) at CT remain limited.Purpose: This was an observational study to describe the prevalence of INOCA defined at coronary CT angiography with CT perfusion imaging and associated clinical and atherosclerotic characteristics. The analysis was also performed for the combination of invasive coronary angiography (ICA) and SPECT as a secondary aim.Materials and Methods: The prospective CORE320 study (ClinicalTrials.gov: NCT00934037) enrolled participants between November 2009 and July 2011 who were symptomatic and referred for clinically indicated ICA. Participants underwent CT angiography, rest-adenosinestress CT perfusion, and rest-stress SPECT prior to ICA. For this ancillary study, the following three phenotypes were considered, using either CT angiography/CT perfusion or ICA/SPECT data: (a) participants with obstructive (>= 50%) stenosis, (b) participants with no obstructive stenosis but ischemia (ie, INOCA) on the basis of abnormal perfusion imaging results, and (c) participants with no obstructive stenosis and normal perfusion imaging results. Clinical characteristics and CT angiography athero-scleroticplaque measures were compared by using the Pearson chi(2) or Wilcoxon rank-sum test.Results: A total of 381 participants (mean age, 62 years [interquartile range, 56-68 years]; 129 [34%] women) were evaluated. A total of 31 (27%) of 115 participants without obstructive (>= 50%) stenosis at CT angiography had abnormal CT perfusion findings. The corresponding value for ICA/SPECT was 45 (30%) of 151. The prevalence of INOCA was 31 (8%) of 381 (95% confidence interval [CI]: 5%, 11%) with CT angiography/CT perfusion and 45 (12%) of 381 (95% CI: 9%, 15%) with ICA/SPECT. Participants with CT-defined INOCA had greater total atheroma volume (118 vs 60 mm(3), P =.008), more positive remodeling (13% vs 1%, P =.006), and greater low-attenuation atheroma volume (20 vs 10 mm(3), P =.007) than participants with no obstructive stenosis and no ischemia. Comparisons for ICA/SPECT showed similar trends.Conclusion: In CORE320, ischemia and no obstructivestenosis (INOCA) prevalence was 8% and 12% at CT angiography/CT perfusion and invasive coronary angiography/SPECT, respectively. Participants with INOCA had greater atherosclerotic burden and more adverse plaque features at CT compared with those with no obstructive stenosis and no ischemia. (C) RSNA, 2019Cardiolog

Diagnostic accuracy of semi-automatic quantitative metrics as an alternative to expert reading of CT myocardial perfusion in the CORE320 study

Cardiolog

Polypill for the prevention of cardiovascular disease (PolyIran): Study design and rationale for a pragmatic cluster randomized controlled trial

Background The complexity of treatment regimens, costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage. The polypill, a fixed dose combination pill of established drugs, is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events (MCVE). Design and methods The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized to either non-pharmacological preventive interventions alone (minimal care arm) or together with a polypill (polypill arm) comprising hydrochlorothiazide, aspirin, atorvastatin and either enalapril or valsartan. This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers (Behvarz) to the participants. The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infarction, unstable angina, sudden death, heart failure, coronary artery revascularization procedures, and non-fatal and fatal stroke. Trial status From February 2011 to April 2013, 8410 individuals (236 clusters) attended the eligibility assessment. Of those, 3421 in the polypill arm and 3417 in the minimal care arm were eligible. The study is ongoing. Conclusion The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial. If the polypill strategy proves effective, it may be implemented to prevent cardiovascular disease in developing countries. © European Society of Cardiology 2014