Citations

AbstractBackgroundCholelithiasis is a frequent complication in pediatric sickle cell disease (SCD). Though it is standard practice to perform a cholecystectomy in pediatric SCD patients with symptoms of cholelithiasis, the use of elective cholecystectomy for asymptomatic patients remains controversial.ProcedureRecords of 191 pediatric sickle cell patients with cholelithiasis who underwent cholecystectomy were retrospectively reviewed. Patients classified as follows: (i) elective—no preoperative symptoms, cholelithiasis on screening ultrasound, comprehensive preoperative plan; (ii) symptomatic—preoperative symptoms of cholelithiasis on diagnostic ultrasound, comprehensive preoperative plan; or (iii) emergent—hospitalization for acute cholecystitis symptoms, cholelithiasis on diagnostic ultrasound, limited preoperative preparation. We compared the morbidity of cholecystectomy by examining pre‐ and post‐cholecystectomy hospital admission days, length of stay for cholecystectomy, and surgical complications.ResultsPatients with SCD underwent a total of 191 cholecystectomies over a 10‐year period: 51 elective, 110 symptomatic, and 30 emergent. Patients who required emergent cholecystectomy had a longer postoperative hospitalization time than elective or symptomatic cholecystectomy (7.3 vs 4.3, P < 0.001). Baseline values for total bilirubin and aspartate aminotransferase (AST) were significantly elevated (P < 0.02 and P < 0.07, respectively) in patients requiring emergent cholecystectomy.ConclusionsThis represents the largest reported retrospective review of pediatric cholelithiasis and cholecystectomy in SCD to date. These data strongly suggest that elective cholecystectomy decreases morbidity associated with emergent cholecystectomy. The overall outcomes for symptomatic and elective patients are favorable. However, our study indicates the need for prospective studies to identify clinical indicators for those emergent patients.

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.

AbstractAlthough studies suggest that patients with limited health literacy and/or low numeracy skills may stand to gain the most from shared decision making (SDM), the impact of these conditions on the effective implementation of SDM in the emergency department (ED) is not well understood. In this article from the proceedings of the 2016 Academic Emergency Medicine Consensus Conference on Shared Decision Making in the Emergency Department we discuss knowledge gaps identified and propose consensus‐driven research priorities to help guide future work to improve SDM for this patient population in the ED.

Abstract Donor organ shortage is the main limitation to liver transplantation as a treatment for end-stage liver disease and acute liver failure. Liver regenerative medicine may in the future offer an alternative form of therapy for these diseases, be it through cell transplantation, bioartificial liver (BAL) devices, or bioengineered whole organ liver transplantation. All three strategies have shown promising results in the past decade. However, before they are incorporated into widespread clinical practice, the ideal cell type for each treatment modality must be found, and an adequate amount of metabolically active, functional cells must be able to be produced. Research is ongoing in hepatocyte expansion techniques, use of xenogeneic cells, and differentiation of stem cell-derived hepatocyte-like cells (HLCs). HLCs are a few steps away from clinical application, but may be very useful in individualized drug development and toxicity testing, as well as disease modeling. Finally, safety concerns including tumorigenicity and xenozoonosis must also be addressed before cell transplantation, BAL devices, and bioengineered livers occupy their clinical niche. This review aims to highlight the most recent advances and provide an updated view of the current state of affairs in the field of liver regenerative medicine.

Key points Intracellular pH regulation is vital to neurons as nerve activity produces large and rapid acid loads in presynaptic terminals. Rapid clearance of acid loads is necessary to maintain control of neurotransmission, but neuronal acid clearance mechanisms remain poorly understood. Glutamate is loaded into synaptic vesicles via the vesicular glutamate transporter (VGLUT), a mechanism conserved across phyla, and this study reports a previously unknown role for VGLUT as an acid‐extruding protein when deposited in the plasmamembrane during exocytosis. The finding was made in Drosophila (fruit fly) larval motor neurons through a combined pharamacological and genetic dissection of presynaptic pH homeostatic mechanisms. A dual role for VGLUT serves to integrate neuronal activity and pH regulation in presynaptic nerve terminals. AbstractNeuronal activity can result in transient acidification of presynaptic terminals, and such shifts in cytosolic pH (pHcyto) probably influence mechanisms underlying forms of synaptic plasticity with a presynaptic locus. As neuronal activity drives acid loading in presynaptic terminals, we hypothesized that the same activity might drive acid efflux mechanisms to maintain pHcyto homeostasis. To better understand the integration of neuronal activity and pHcyto regulation we investigated the acid extrusion mechanisms at Drosophila glutamatergic motorneuron terminals. Expression of a fluorescent genetically encoded pH indicator, named ‘pHerry’, in the presynaptic cytosol revealed acid efflux following nerve activity to be greater than that predicted from measurements of the intrinsic rate of acid efflux. Analysis of activity‐induced acid transients in terminals deficient in either endocytosis or exocytosis revealed an acid efflux mechanism reliant upon synaptic vesicle exocytosis. Pharmacological and genetic dissection in situ and in a heterologous expression system indicate that this acid efflux is mediated by conventional plasmamembrane acid transporters, and also by previously unrecognized intrinsic H+/Na+ exchange via the Drosophila vesicular glutamate transporter (DVGLUT). DVGLUT functions not only as a vesicular glutamate transporter but also serves as an acid‐extruding protein when deposited on the plasmamembrane.

Objectives To identify geriatric obesity interventions that can guide clinical recommendations. Design Systematic review using Medline (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, CINAHL , EMBASE (Ovid), and Psyc INFO (Proquest) from January 1, 2005, to October 12, 2015, to identify English‐language randomized controlled trials. Participants Individuals aged 60 and older (mean age ≥65) and classified as having obesity (body mass index ≥30 kg/m 2 ). Interventions Behavioral weight loss interventions not involving pharmacological or procedural therapies lasting 6 months or longer. Measurements Two investigators performed the systematic review using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses criteria and achieved a high concordance rate (97.3%) in summarizing the primary outcomes. The three primary outcomes were weight loss, physical performance, and quality of life. Results Of 5,741 citations, 19 were included. (Six studies were unique, and the remaining 13 were based on the same study population.) Duration ranged from 6 to 18 months (n = 405 participants, age range 66.7–71.1). Weight loss in the intervention groups ranged from 0.5 to 10.7 kg (0.1–9.3%). Five studies had a resistance exercise program accompanying a dietary component. Greater weight loss was observed in groups with a dietary component than those with exercise alone. Exercise alone led to better physical function but no significant weight loss. Combined dietary and exercise components led to the greatest improvement in physical performance measures and quality of life and mitigated reductions in muscle and bone mass observed in diet‐only study arms. Heterogeneous outcomes were observed, which limited the ability to synthesize the data quantitatively. Conclusions The evidence supporting geriatric obesity interventions to improve physical function and quality of life is of low to moderate quality. Well‐designed trials are needed in this population.

Introduction.Pneumocystispneumonia (PCP) is rising in the non-HIV population and associates with higher morbidity and mortality. The aggressive immunosuppressive regimens, as well as the lack of stablished guidelines for chemoprophylaxis, are likely contributors to this increased incidence. Herein, we have explored the underlying conditions, immunosuppressive therapies, and clinical outcomes of PCP in HIV-negative patients.Methods. Retrospective analysis of PCP in HIV-negative patients at Mayo Clinic from 2006–2010. The underlying condition, immunosuppressive therapies, coinfection, and clinical course were determined. PCP diagnosis required symptoms of pneumonia and identification of the organisms by visualization or by a real-time polymerase chain reaction.Results. A total of 128 cases of PCP were identified during the study period. Hematological malignancies were the predisposing condition for 50% of the patients. While 87% had received corticosteroids or other immunosuppressive therapies for >4 weeks prior to the diagnosis, only 7 were receiving PCP prophylaxis. Up to 43% of patients were not on daily steroids. Sixty-seven patients needed Intensive Care Unit (ICU) and 53 received mechanical ventilation. The mortality for those patients requiring ICU was 40%.Conclusions. PCP diagnosis in the HIV-negative population requires a high level of suspicion even if patients are not receiving daily corticosteroids. Mortality remains high despite adequate treatment.