Incidence of Reoperation After Surgical Procedure for Left Ventricular Outflow Tract Obstruction in Children and Young Adults

BackgroundThe common causes of subaortic left ventricular outflow tract obstruction (LVOTO) are hypertrophic cardiomyopathy (HCM) and membranous/tunnel subaortic stenosis (SAS). Reoperation after corrective surgery may be due to recurrent disease, associated congenital defects, or complications of the initial procedure. This study compares the late outcomes of young patients with HCM and SAS.MethodsWe studied clinical, echocardiographic, and operative data of patients ≤21 years of age at the time of surgery for LVOTO between August 1963 and August 2018. We stratified patients into HCM (n = 152) and congenital SAS (n = 63) groups and compared survival and cumulative incidence of reoperation.ResultsAt initial repair, patients with HCM were older than patients with SAS (median [interquartile range] age, 15 [10-19] years vs 8 [5-13] years; P < .001), and patients with HCM were more symptomatic with dyspnea (P < .001), chest pain (P = .002), and presyncope/syncope (P = .005). Thirty-day mortality was 1.3% vs 0% for HCM and SAS groups. During a median follow-up of 13.1 years, survival was similar through the first 10 years; but during the second decade, patients with HCM had poorer survival (survival at 20 years, 80% vs 91% for patients with SAS; P = .007). Ten years after repair, reoperation for recurrent LVOTO was performed in 5% of patients with HCM vs 31% in those with SAS (P < .001).ConclusionsIn this surgical cohort, patients with HCM were more symptomatic preoperatively than those with SAS. Late survival of patients with SAS was superior to that of patients with HCM despite a greater need for reoperation.     

Lipids,Lipid-Lowering Therapy,and Neuropathy: A Narrative Review

Statins, or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are the mainstay of treatment for hypercholesterolemia as they effectively reduce LDL-C levels and risk of atherosclerotic cardiovascular disease. Apart from hyperglycemia, dyslipidemia and HDL dysfunction are known risk factors for neuropathy in people with obesity and diabetes. Although there are case reports of statin-induced neuropathy, ad hoc analyses of clinical trials and observational studies have shown that statins may improve peripheral neuropathy. However, large randomized controlled trials and meta-analyses of cardiovascular outcome trials with statins and other lipid-lowering drugs have not reported on neuropathy outcomes. Because neuropathy was not a prespecified outcome in major cardiovascular trials, one cannot conclude whether statins or other lipid-lowering therapies increase or decrease the risk of neuropathy. The aim of this review was to assess if statins have beneficial or detrimental effects on neuropathy and whether there is a need for large well-powered interventional studies using objective neuropathy end points.     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

Biological Disease-Modifying Antirheumatic Drugs and Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis: A Danish Cohort Study

ObjectivesClinical trials have shown a beneficial effect from biological disease-modifying antirheumatic drugs (bDMARDs) on hand or axial bone loss in patients with rheumatoid arthritis; however, it is unclear if this translates to a reduced fracture risk. We investigated the effect of bDMARDs on osteoporotic fracture risk compared to no biological treatment in rheumatoid arthritis.MethodsA cohort of patients with rheumatoid arthritis aged 18+ from DANBIO was linked to population-based health registries in Denmark (2006-2016). Adopting a prevalent new-user design, we matched bDMARD users to bDMARD-naïve patients using time-conditional propensity scores. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, and forearm) was estimated among the matched patients by Cox proportional hazards models.ResultsOut of 24,678 patients with rheumatoid arthritis, 4265 bDMARD users were matched to the same number of bDMARD-naïve patients (mean age 56.2 years, 74% female). During follow-up, 229 osteoporotic fractures occurred among bDMARD users and 205 fractures among bDMARD-naïve patients (incidence rates 12.1 and 13.0 per 1000 person-years, respectively). The use of bDMARDs was not associated with a reduced risk of osteoporotic fractures among patients with rheumatoid arthritis (hazard ratio 0.97, 95% confidence interval 0.78-1.20), compared with no biological treatment. The risk estimates were similar for all osteoporotic fracture sites.ConclusionWe found no independent beneficial effect from using bDMARDs on reducing the risk of osteoporotic fractures in patients with rheumatoid arthritis.     

Intestinal Dysbiosis in the Infant and the Future of Lacto-Engineering to Shape the Developing Intestinal Microbiome

PurposeThe goal of this study was to review the role of human milk in shaping the infant intestinal microbiota and the potential of human milk bioactive molecules to reverse trends of increasing intestinal dysbiosis and dysbiosis-associated diseases.MethodsThis narrative review was based on recent and historic literature.FindingsHuman milk immunoglobulins, oligosaccharides, lactoferrin, lysozyme, milk fat globule membranes, and bile salt–stimulating lipase are complex multifunctional bioactive molecules that, among other important functions, shape the composition of the infant intestinal microbiota.ImplicationsThe co-evolution of human milk components and human milk–consuming commensal anaerobes many thousands of years ago resulted in a stable low-diversity infant microbiota. Over the past century, the introduction of antibiotics and modern hygiene practices plus changes in the care of newborns have led to significant alterations in the intestinal microbiota, with associated increases in risk of dysbiosis-associated disease. A better understanding of mechanisms by which human milk shapes the intestinal microbiota of the infant during a vulnerable period of development of the immune system is needed to alter the current trajectory and decrease intestinal dysbiosis and associated diseases.