Heterogeneity of weight loss after gastric bypass,sleeve gastrectomy,and adjustable gastric banding

Background

Laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding all lead to substantial weight loss in obese patients. Long-term weight loss can be highly variable beyond 1-year postsurgery. This study examines and compares the frequency distribution of weight loss and lack of treatment effect rates after laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding.

Intervention for arch obstruction after the Norwood procedure: Prevalence,associated factors,and practice variability

Objective

Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality.

The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

Additive Effects of Sevoflurane and Propofol on γ-Aminobutyric Acid Receptor Function

Background: Previous studies have shown that propofol and sevoflurane enhance the function of [gamma]-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.

Methods: Wild-type [alpha]1, [beta]2, [gamma]2s GABAA receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 [mu]m [gamma]-aminobutyric acid (GABA), 0-10 [mu]m propofol, and 0-1,650 [mu]m sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results: Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA.     

Mesogonadal shunts for extrahepatic portal vein thrombosis and variceal hemorrhage.

Extrahepatic portal vein thrombosis (EHPVT) may occur in children or adults and usually comes to clinical attention due to complications of portal hypertension such as variceal hemorrhage. A variety of standard surgical techniques exist to manage these patients, but when these fail surgical options are limited. We describe two novel portosystemic shunts that utilize the gonadal vein as an autologous conduit. Four patients were evaluated for EHPVT with variceal bleeding. None of the patients were candidates for a standard splenorenal shunt due to prior surgical procedures. The first patient underwent a left mesogonadal shunt and the remaining 3 patients underwent a right mesogonadal shunt. Postoperative ultrasound or computed tomography (CT) scan confirmed early patency of the shunt in each patient. There have been no further episodes of variceal hemorrhage with follow-up of 3.5 years in the child who underwent the left mesogonadal shunt, and 17, 19, and 20 months in the patients who underwent the right mesogonadal shunt. Three of the 4 shunts remain patent. One shunt thrombosis occurred in a patient homozygous for the Factor V Leiden mutation despite anticoagulation with coumadin. This is the first report of the successful use of the gonadal vein as an in situ conduit for constructing a portosystemic shunt. In conclusion, the right and left mesogonadal shunts may be useful as salvage operations for patients with EHPVT who have failed standard surgical shunt procedures.