An immediate post op and follow up assessment of circulating adipo-cytokines after bariatric surgery in morbid obesity.

BACKGROUND: Bariatric surgery has emerged as a promising treatment for improving adipose tissue dysfunction in obesity, but the mechanisms for such amelioration are still not known. This study comprehensively explores a panel of adipo-cytokines in individuals with obesity undergoing bariatric surgery, in conjunction with markers of insulin resistance, at three time points i.e., pre-op, immediate post-op and 6 months post-surgery. METHODS: It is a case-control prospective study among obese individuals undergoing bariatric surgery (BMI ≥35 kg/m2, n=30) and non-obese subjects (BMI <25 kg/m2, n=30), comparing the levels of serum adiponectin, resistin, C-Reactive Protein (CRP), Interleukin (IL)-6 and 8, Monocyte chemoattractant protein (MCP)-1 and Tumor necrosis factor (TNF)-α between them. The same were followed at immediate and 6-month post-op periods in the former group. The serum markers were correlated with the markers of Insulin resistance like HOMA-IR, HOMA-ß and QUICKI. RESULTS: A significant increase in adiponectin was seen after weight loss in obese group (17.54 ± 1.31 µg/mL at baseline vs 68.76 ± 1.84 µg/mL at 6- month post-surgery). CRP being an acute phase protein showed significant higher levels at immediate post-op period but declined even below its baseline at 6 months after surgery (33.34 ± 16.85 µg/mL at baseline vs 59.85 ± 23.12 µg/mL at immediate post-op vs 9.66 ± 1.84 µg/mL at 6 months post-operatively). Few inconsistencies were observed in the trajectories of IL-6 and TNF-α, while other pro-inflammatory markers indicated resolution after surgery. CONCLUSION: Bariatric surgery alleviated the systemic inflammation, correlating with improved insulin resistance in individuals with obesity.

Long QT-Syndrome With Torsades de Pointes Managed Considering Financial Constraints Faced by the Patient.

Long QT syndrome (LQTS) is a rare arrhythmogenic condition characterized by abnormally long QT intervals on an electrocardiogram. The prevalence varies between 1 in 3000 and 1 in 10,000 but often remains undiagnosed. It is responsible for 3000 to 4000 sudden deaths among children and adults in the United States alone. LQTS can lead to torsades de pointes which is seen as twisting of QRS complex on electrocardiogram. We report a case of a 35-year-old patient with LQTS who presented with syncope and was found to have torsades de pointes. After acute management the patient was advised for automatic implantable cardioverter defibrillator (AICD) but because of financial constraints, she was placed on beta-blockers and permanent pacemaker.

Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis.

BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. FUNDING: The German Federal Ministry of Education and Research and Echosens.

Bariatric Surgery in Nonalcoholic Fatty Liver Disease (NAFLD): Impact Assessment Using Paired Liver Biopsy and Fibroscan.

BACKGROUND: Bariatric surgery is associated with a positive impact on the degree of hepatic steatosis and inflammation in nonalcoholic associated fatty liver disease (NAFLD), although its effect on fibrosis is contentious. The role of Fibroscan in the post-bariatric assessment of hepatic steatosis and fibrosis is unclear. OBJECTIVES: This work aims to study the impact of bariatric surgery on the course of NAFLD using both invasive (liver biopsy) and non-invasive tests (biochemical parameters and Fibroscan). METHODS: In this prospective study, the impact of bariatric surgery on the course of NAFLD was assessed using paired liver biopsy (intra-operative and post-bariatric surgery 1-year follow-up). The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) cutoffs for the assessment of hepatic fibrosis and steatosis, respectively, were calculated in both pre- and post-bariatric settings. RESULTS: Fifty-eight patients (70.7% females, mean age 39.2 years) underwent paired liver biopsy. Post-bariatric surgery 1-year liver biopsy showed significant improvement in all the histopathological parameters of NAFLD. The mean NAFLD Activity Score declined from 2.81 (± 1.08) to 1.31 (± 1.39) post-bariatric surgery. Thirty (51.7%) patients showed improvement in fibrosis, eighteen (31%) no change, and ten (17.2%) had worsening. Worsening of fibrosis was associated with a higher median age of 44.5 versus 38 years (p value = 0.033). The CAP cutoff values for the various stages of hepatic steatosis were higher pre-operatively as compared with those obtained post-bariatric surgery. CONCLUSIONS: Bariatric surgery is associated with significant improvement in histopathological parameters of NAFLD. Fibroscan shows good diagnostic accuracy in detecting advanced stage and grade of NAFLD.

Body mass index-based controlled attenuation parameter cut-offs for assessment of hepatic steatosis in non-alcoholic fatty liver disease.

BACKGROUND AND AIM: In patients with liver disease, etiology and body mass index (BMI) affects controlled attenuation parameter (CAP) assessment using FibroScan. We aimed to assess the performance characteristics of CAP for hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) stratified into obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) subgroups. METHODS: In this prospective study, 219 consecutive adult NAFLD patients, with an available FibroScan value (liver stiffness measurement-[LSM] and CAP) and liver biopsy, were included. Receiver operating characteristic curves were used for assessment of the CAP cut-off values predicting different stages of hepatic steatosis. RESULTS: The mean ± standard deviation age of patients was 39.7 ± 10.5 years, 116 (53%) were males, and median (interquartile range) BMI was 31.8 (25.7-43.8) kg/m2. One hundred (45.7%) and 119 (54.3%) patients were non-obese and obese, respectively. The median values of CAP and LSM were significantly higher among obese patients as compared with the non-obese ones: 333 (304-368) vs. 320 (296-345) dB/m, p = 0.002 and 8.3 (6.1-11.4) vs. 6.6 (5.7-10.3) kPa, p = 0.012, respectively. Among non-obese NAFLD, optimal CAP cut-off values for steatosis (S) ≥ S1, ≥ S2, and ≥ S3 were 275 dB/m, 319 dB/m, and 337 dB/m, respectively. The corresponding CAP values among obese patients were higher as 285 dB/m, 340 dB/m, and 355 dB/m, respectively. BMI independently predicted CAP on multivariate analysis. The discordance of 2-grades between CAP and biopsy measured steatosis was seen in 13% in non-obese and 19.3% in obese NAFLD. CAP overestimated steatosis more often than underestimating it, with a higher proportion in obese NAFLD. CONCLUSION: In patients with NAFLD, interpretation of CAP requires consideration of BMI.

Controlled Attenuation Parameter for Assessment of Hepatic Steatosis in Indian Patients.

BACKGROUND/AIMS: The gold standard method for measurement of hepatic steatosis is liver histology. Controlled Attenuation Parameter (CAP) can measure hepatic steatosis non-invasively. We aimed to assess the accuracy of CAP for detection of hepatic steatosis. METHODS: A total of 462 patients (May 2012-January 2017)-89 non-alcoholic fatty liver disease, 182 chronic hepatitis B, 88 chronic hepatitis C and 103 patients with other etiologies who underwent simultaneous liver biopsy and CAP estimation using Transient Elastography (TE) were included. Steatosis was graded as S0: steatosis in 0-5% of hepatocytes, S1: 6-33%, S2: 34-66% and S3: 67-100%. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the accuracy of CAP in detecting hepatic steatosis. Predictors of CAP were assessed by multivariate linear regression model. RESULTS: The mean age ± SD was 33.8 ± 11.6 years; 296 (64.1%) were males. On liver histology, steatosis grades S0, S1, S2 and S3 were seen in 331 (71.6%), 74 (16.0%), 39 (8.4%) and 18 (3.9%), respectively. The median CAP (IQR) values for S0, S1, S2, and S3 steatosis were 206 (176-252) dB/m, 295 (257-331) dB/m, 320 (296-356) dB/m, and 349 (306-363) dB/m, respectively. For estimation of ≥S1, ≥S2, and ≥S3 using CAP, AUROC were 0.879, 0.893, and 0.883, respectively. In multivariate analysis, only BMI (OR 1.18; CI, 1.11-1.26, P < 0.001) and grade of hepatic steatosis (grade 1, OR, 3.94; 95% CI, 1.58-9.84, P = 0.003; grade 2, OR 42.04; 95% CI, 4.97-355.31, P = 0.001 and grade 3, OR 35.83; 95% CI 4.31-297.61, P = 0.001) independently predicted CAP. CONCLUSIONS: CAP detects hepatic steatosis with good accuracy in Indian patients with various etiologies.

Infection is the chief cause of mortality and non-death censored graft loss in the first year after renal transplantation in a resource limited population: A single centre study.

AIM: Few studies have assessed the impact of infections after renal transplantation (RTX) in low and middle income countries. This single centre study aimed to delineate the profile and impact of infections requiring hospitalization (IRH) occurring in the first year after RTX in India. METHOD: Patients who underwent RTX between July 2012 and June 2015 were followed up for 12 months after transplantation. RESULTS: 60.2% of the 387 patients studied had at least one IRH and total 492 infections were diagnosed. The most common were urinary tract (30.3%), gastrointestinal (17.1%) and pulmonary (11.2%) infections. Viral aetiology (33.3%) was most frequent, followed by bacterial (23.6%), parasitic (5.1%), tuberculosis (4.5%), and fungal infections (3.9%). 86.4% deaths were due to infections. One year patient and graft survival were inferior among recipients with IRH compared to those with no IRH: 91.8% vs. 98.1% (log rank = 0.010) and 90.1% vs. 97.4% (log rank = 0.006) respectively. Average monthly income per family member <5000 Rupees (75 USD), NODAT, and acute rejection were independent risk factors for IRH. CONCLUSION: The profile of IRH is unique involving opportunistic, community-acquired and endemic infections seen in this country. It is the predominant cause of mortality and graft loss in the first year after RTX. Poor economic status is an important determinant of IRH in our population.

Rehabilitation Therapy in Peripheral Arterial Disease.

Peripheral arterial disease (PAD) is the result of atherosclerosis in the lower limb arteries, which can give rise to intermittent claudication (IC), limb ulceration, infections, and, in some circumstances, amputation. As a result of PAD, patients are frequently limited in both walking duration and speed. These ambulatory deficits impact both functional capacity and quality of life. The prevalence of PAD is increasing, and patients with this diagnosis have high cardiovascular morbidity and mortality. A comprehensive approach is required to improve outcomes in patients with PAD and include tobacco cessation, pharmacologic management of metabolic fitness, risk-factor modification, and exercise training. Supervised exercise programs significantly improve functional capacity and quality of life in addition to reducing IC. These programs reduce morbidity and mortality and are cost-effective; yet they are uncommonly prescribed. Supervised exercise training is an accepted intervention in the PAD population and has been included in both Canadian and American guidelines for PAD management. This review describes (1) key background information related to PAD, (2) the initial approach to PAD diagnosis, (3) pharmacologic management options, (4) risk-factor modification, and (5) the currently accepted approach to exercise training. Key recommendations for enhancing PAD care in a Canadian context are also discussed.

Optimizing Value From Cardiac Rehabilitation: A Cost-Utility Analysis Comparing Age, Sex, and Clinical Subgroups.

OBJECTIVE: To assess the cost utility of a center-based outpatient cardiac rehabilitation program compared with no program within patient subgroups on the basis of age, sex, and clinical presentation (acute coronary syndrome [ACS] or non-ACS). METHODS: We performed a cost-utility analysis from a health system payer perspective to compare cardiac rehabilitation with no cardiac rehabilitation for patients who had a cardiac catheterization. The Markov model was stratified by clinical presentation, age, and sex. Clinical, quality-of-life, and cost data were provided by the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology. RESULTS: The incremental cost per quality-adjusted life-year (QALY) gained for cardiac rehabilitation varies by subgroup, from $18,101 per QALY gained to $104,518 per QALY gained. There is uncertainty in the estimates due to uncertainty in the clinical effectiveness of cardiac rehabilitation. Overall, the probabilistic sensitivity analysis found that 75% of the time participation in cardiac rehabilitation is more expensive but more effective than not participating in cardiac rehabilitation. CONCLUSION: The cost-effectiveness of cardiac rehabilitation varies depending on patient characteristics. The current analysis indicates that cardiac rehabilitation is most cost effective for those with an ACS and those who are at higher risk for subsequent cardiac events. The findings of the current study provide insight into who may benefit most from cardiac rehabilitation, with important implications for patient referral patterns.

Feasibility of community-based screening for cardiovascular disease risk in an ethnic community: the South Asian Cardiovascular Health Assessment and Management Program (SA-CHAMP).

BACKGROUND: South Asian Canadians experience disproportionately high rates of cardiovascular disease (CVD). The goal of this qualitative study was to determine the feasibility of implementing a sustainable, culturally adapted, community-based CVD risk factor screening program for this population. METHODS: South Asians (≥ 45 years) in Calgary, Alberta underwent opportunistic cardiovascular risk factor screening by lay trained volunteers at local religious facilities. Those with elevated blood pressure (BP) or ≥ 1 risk factor underwent point of care cholesterol testing, 10-year CVD risk calculation, counseling, and referral to family physicians and local culturally tailored chronic disease management (CDM) programs. Participants were invited for re-screening and were surveyed about health system follow-up, satisfaction with the program and suggestions for improvement. Changes in risk factors from baseline were estimated using McNemar's test (proportions) and paired t-tests (continuous measures). RESULTS: Baseline assessment was completed for 238 participants (median age 64 years, 51% female). Mean TC, HDL and TC/HDL were 5.41 mmol/L, 1.12 mmol/L and 4.7, respectively. Mean systolic and diastolic blood pressures (mmHg) were 129 and 75 respectively. Blood pressure and TC/HDL ratios exceeded recommended targets in 36% and 58%, respectively, and 76% were at high risk for CVD. Ninety-nine participants (47% female) attended re-screening. 82% had accessed health care providers, 22% reported medication changes and 3.5% had attended the CDM programs. While BP remained unchanged, TC and TC/HDL decreased and HDL increased significantly (mean differences: -0.52 mmol/L, -1.04 and +0.07 mmol/L, respectively). Participants were very satisfied (80%) or satisfied (20%) with the project. Participants suggested screening sessions and CDM programs be more accessible by: delivering evening or weekends programs at more sites, providing transportation, offering multilingual programs/translation assistance, reducing screening wait times and increasing numbers of project staff. CONCLUSIONS: SA-CHAMP demonstrated the feasibility and value of implementing a lay volunteer-led, culturally adapted, sustainable community-based CVD risk factor screening program in South Asian places of worship in Calgary, Alberta, Canada. Subsequent screening and CDM programs were refined based on the learnings from this study. Further research is needed to determine physician and patient factors associated with uptake of and adherence to risk reduction strategies.

Post-exercise assessment of cardiac repolarization alternans in patients with coronary artery disease using the modified moving average method.

OBJECTIVES: We sought to evaluate the utility of T-wave alternans (TWA) assessment in the immediate post-exercise period to identify and validate cutpoints for the modified moving average (MMA) assessment method. BACKGROUND: The presence of TWA is associated with an increased risk of cardiovascular death (CVD). The immediate post-exercise period, where increased physiologic stress and minimal surface artifact coexist, appears ideal to implement the MMA method. METHODS: A test (n = 322) and validation cohort (n = 681) provided 1,003 patients with coronary artery disease (CAD). We assessed TWA immediately after exercise. The outcomes, CVD and mortality, were adjudicated independent of the TWA results. RESULTS: During 48 months of follow-up 85 deaths, 54 categorized as CVD (64%), were observed. A linear relationship between the magnitude of TWA and the risk of CVD was identified. As a continuous measure TWA voltage was equivalent to ejection fraction in predicting the risk of CVD. To facilitate clinical application, a sensitive, modest predictive accuracy (20 microV) and a specific, greater predictive accuracy MMA cutpoint (60 microV) were identified and validated. Each cutpoint was associated with a 2.5-fold greater risk of CVD, independent of other important variables, including ejection fraction. CONCLUSIONS: Post-exercise assessment of TWA using the MMA method is a strong, independent predictor of risk in patients with CAD. The 20-microV cutpoint (87% sensitivity) appears to be most suitable in higher-risk patients, whereas the 60-microV cutpoint (95% specificity) appears more appropriate when TWA is used as a single screening test in those at lower risk. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; NCT00399503).

Noninvasive risk assessment early after a myocardial infarction the REFINE study.

OBJECTIVES: This study sought to determine whether combined assessment of autonomic tone plus cardiac electrical substrate identifies most patients at risk of serious events after myocardial infarction (MI) and to compare assessment at 2 to 4 weeks versus 10 to 14 weeks after MI. BACKGROUND: Methods to identify most patients at risk of serious events after MI are required. METHODS: Patients (n = 322) with an ejection fraction (EF) <0.50 in the initial week after MI were followed up for a median of 47 months. Serial assessment of autonomic tone, including heart rate turbulence (HRT), electrical substrate, including T-wave alternans (TWA), and EF was performed, interpreted blinded, and categorized using pre-specified cut-points where available. The primary outcome was cardiac death or resuscitated cardiac arrest. All-cause mortality and fatal or nonfatal cardiac arrest were secondary outcomes. RESULTS: Mean EF significantly increased over the initial 8 weeks after MI. Testing 2 to 4 weeks after MI did not reliably identify patients at risk, whereas testing at 10 to 14 weeks did. The 20% of patients with impaired HRT, abnormal exercise TWA, and an EF <0.50 beyond 8 weeks post-MI had a 5.2 (95% confidence interval [CI] 2.4 to 11.3, p < 0.001) higher adjusted risk of the primary outcome. This combination identified 52% of those at risk, with good positive (23%; 95% CI 17% to 26%) and negative (95%; 95% CI 93% to 97%) accuracy. Similar results were observed for the secondary outcomes. CONCLUSIONS: Impaired HRT, abnormal TWA, and an EF <0.50 beyond 8 weeks after MI reliably identify patients at risk of serious events. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; http://www.clinicaltrials.gov/ct/show/NCT00399503?order=1; NCT00399503).