PET-CT reveals increased intestinal glucose uptake after gastric surgery

BackgroundMechanisms of metabolic improvement after bariatric surgery remain incompletely understood. Intestinal glucose uptake is increased after gastric bypass in rodents, potentially contributing to reduced blood glucose and type 2 diabetes remission.ObjectiveWe assessed whether intestinal glucose uptake is increased in humans after gastric surgery.SettingUniversity Hospital, United States.MethodsIn a retrospective, case-control cohort study, positron emission tomography-computerized tomography scans performed for clinical indications were analyzed to quantify intestinal glucose uptake in patients with or without history of gastric surgery. We identified 19 cases, defined as patients over age 18 with prior gastric surgery (Roux-en-Y gastric bypass [n = 10], sleeve gastrectomy [n = 1], or Billroth I [n = 2] or II gastrectomy [n = 6]), and 43 controls without gastric surgery, matched for age, sex, and indication for positron emission tomography-computerized tomography. Individuals with gastrointestinal malignancy or metformin treatment were excluded. Images were obtained 60 minutes after ¹⁸F-fluorodeoxyglucose injection (4.2 MBq/kg), and corrected by attenuation; noncontrast low-dose computerized tomography was obtained in parallel. Fused and nonfused images were analyzed; standardized uptake values were calculated for each region by volumes of interest at the region of highest activity.ResultsBoth standardized uptake values maximum and mean were significantly increased by 41% to 98% in jejunum, ascending, and transverse colon in patients with prior gastric surgery (P < .05 versus controls).ConclusionIntestinal glucose uptake is increased in patients with prior gastric surgery. Prospective studies are important to dissect the contributions of weight loss, dietary factors, and systemic metabolism, and to determine the relationship with increased insulin-independent glucose uptake and reductions in glycemia.     

Late morbidity and mortality in adult survivors of childhood glioma with neurofibromatosis type 1: report from the Childhood Cancer Survivor Study

PurposeNeurofibromatosis type 1 (NF1) is associated with tumor predisposition and nonmalignant health conditions. Whether survivors of childhood cancer with NF1 are at increased risk for poor long-term health outcomes is unknown.MethodsOne hundred forty-seven 5+ year survivors of childhood glioma with NF1 from the Childhood Cancer Survivor Study were compared with 2629 non-NF1 glioma survivors and 5051 siblings for late mortality, chronic health conditions, and psychosocial, neurocognitive, and socioeconomic outcomes.ResultsSurvivors with NF1 (age at diagnosis: 6.8 ± 4.8 years) had greater cumulative incidence of late mortality 30 years after diagnosis (46.3% [95% confidence interval: 23.9–62.2%]) compared with non-NF1 survivors (18.0% [16.1–20.0%]) and siblings (0.9% [0.6–1.2%]), largely due to subsequent neoplasms. Compared with survivors without NF1, those with NF1 had more severe/life-threatening chronic conditions at cohort entry (46.3% [38.1–54.4%] vs. 30.8% [29.1–32.6%]), but similar rates of new conditions during follow-up (rate ratio: 1.26 [0.90–1.77]). Survivors with NF1 were more likely to report psychosocial impairments, neurocognitive deficits, and socioeconomic difficulties compared with survivors without NF1.ConclusionsLate mortality among glioma survivors with NF1 is twice that of other survivors, due largely to subsequent malignancies. Screening, prevention, and early intervention for chronic health conditions and psychosocial and neurocognitive deficits may reduce long-term morbidity in this vulnerable population.     

Wnt signaling in bone and muscle

Wnt signaling plays key roles in many aspects of development. In this review, we will briefly describe the components of signaling pathways induced by Wnt ligands and then describe the current state of research as this applies to aspects of development and disease as it relates to skeletal muscle and bone. We will conclude with a discussion of the parallels and differences in Wnt signaling in these two contexts and how these pathways are being (or could potentially be) targeted for therapeutic treatment of musculoskeletal diseases.This article is part of a Special Issue entitled “Muscle Bone Interactions”.     

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.