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BackgroundWhile central obesity increases gastroesophageal reflux (GER) by mechanically disrupting the anti‐reflux barrier, limited data exist on pathways by which central obesity may potentiate esophageal injury by non‐mechanical means. Obesity has been associated with an impaired epithelial intestinal barrier.ObjectiveWe aimed to assess the influence of central obesity and reflux on the squamous esophageal epithelial intercellular space diameter (ICSD).MethodsThe ICSD was measured using electron microscopy in esophageal biopsies from individuals who underwent ambulatory pH monitoring and endoscopy. Anthropometric measurements were obtained on all participants. Participants were classified into four groups: with and without central obesity and reflux.ResultsSixteen individuals were studied with four in each study group. The mean ICSD was almost three‐fold greater (p < 0.001) in the group with central obesity without reflux, compared to controls without central obesity and reflux. It was also comparable to the ICSD in groups with acid reflux only and those with both reflux and central obesity.ConclusionsThere is evidence of esophageal squamous ICSD increase in individuals with central obesity who do not have evidence of acid and nonacid reflux on ambulatory pH monitoring. This may reflect a mechanism by which central obesity potentiates reflux‐induced esophageal injury and inflammation.

AbstractIntroductionAlzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders.MethodsWe review the contributions of the MRI core from present and past cycles of ADNI (ADNI‐1, ‐Grand Opportunity and ‐2). We also review plans for the future‐ADNI‐3.ResultsContributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials.DiscussionOver the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.

Background/Objectives. Vagal block therapy (vBloc) is effective for moderate to severe obesity at one year.Subjects/Methods. The ReCharge trial is a double-blind, randomized controlled clinical trial of 239 participants with body mass index (BMI) of 40 to 45 kg/m or 35 to 40 kg/m with one or more obesity-related conditions. Interventions were implantation of either vBloc or Sham devices and weight management counseling. Mixed models assessed percent excess weight loss (%EWL) and total weight loss (%TWL) in intent-to-treat analyses. At 18 months, 142 (88%) vBloc and 64 (83%) Sham patients remained enrolled in the study.Results. 18-month weight loss was 23% EWL (8.8% TWL) for vBloc and 10% EWL (3.8% TWL) for Sham (P<0.0001). vBloc patients largely maintained 12-month weight loss of 26% EWL (9.7% TWL). Sham regained over 40% of the 17% EWL (6.4% TWL) by 18 months. Most weight regain preceded unblinding. Common adverse events of vBloc through 18 months were heartburn/dyspepsia and abdominal pain; 98% of events were reported as mild or moderate and 79% had resolved.Conclusions. Weight loss with vBloc was sustained through 18 months, while Sham regained weight between 12 and 18 months. vBloc is effective with a low rate of serious complications.

Study Design: Evidence-based systematic review. Objectives: To define the optimal treatment of fractures involving the C2 body, including those with concomitant injuries, based upon a systematic review of the literature. Summary of Background Data: Axis body fractures have customarily been treated nonoperatively, but there are some injuries that may require operative intervention. High-quality literature is sparse and there are few class I or class II studies to guide treatment decisions. Materials and Methods: A literature search was conducted using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus (EMBASE, MEDLINE, COMPENDEX). The quality of literature was rated according to a grading tool developed by the Center for Evidence-based Medicine. Operative and nonoperative treatment of axis body fractures were compared using fracture bony union as the primary outcome measure. As risk factors for nonunion were not consistently reported, cases were analyzed individually. Results: The literature search identified 62 studies, of which 10 were case reports which were excluded from the analysis. A total of 920 patients from 52 studies were included. The overall bony union rate for all axis body fractures was 91%. Although the majority of fractures were treated nonoperatively, there has been an increasing trend toward operative intervention for Benzel type III (transverse) axis body fractures. Nearly 76% of axis body fractures were classified as type III fractures, of which 88% united successfully. Nearly all Benzel type I and type II axis body fractures were successfully treated nonoperatively. The risk factors for nonunion included: a higher degree of subluxation, fracture displacement, comminution, concurrent injuries, delay in treatment, and older age. Conclusions: High rates for fracture union are reported in the literature for axis body fractures with nonoperative treatment. High-quality prospective studies are required to develop consensus as to which C2 body fractures require operative fixation.

OBJECT Neuroophthalmological morbidity is commonly associated with large and giant cavernous and supraclinoid internal carotid artery (ICA) aneurysms. The authors sought to evaluate the neuroophthalmological outcomes after treatment of these aneurysms with the Pipeline Embolization Device (PED). METHODS The Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial was an international, multicenter prospective trial evaluating the safety and efficacy of the PED. All patients underwent complete neuroophthalmological examinations both before the PED procedure and at a 6-month follow-up. All examinations were performed for the purpose of this study and according to study criteria. RESULTS In total, 108 patients were treated in the PUFS trial, 98 of whom had complete neuroophthalmological follow-up. Of the patients with complete follow-up, 39 (40%) presented with a neuroophthalmological baseline deficit that was presumed to be attributable to the aneurysm, and patients with these baseline deficits had significantly larger aneurysms. In 25 of these patients (64%), the baseline deficit showed at least some improvement 6 months after PED treatment, whereas in 1 patient (2.6%), the deficits only worsened. In 5 patients (5%), new deficits had developed at the 6-month follow-up, while in another 6 patients (6%), deficits that were not originally assumed to be related to the aneurysm had improved by that time. A history of diabetes was associated with failure of the baseline deficits to improve after the treatment. The aneurysm maximum diameter was significantly larger in patients with a new deficit or a worse baseline deficit at 6 months postprocedure. CONCLUSIONS Patients treated with the PED for large and giant ICA aneurysms had excellent neuroophthalmological outcomes 6 months after the procedure, with deficits improving in most of the patients, very few deficits worsening, and few new deficits developing.

Abstract Objective Clinicians’ ability to use and interpret genetic information depends upon how those data are displayed in electronic health records (EHRs). There is a critical need to develop systems to effectively display genetic information in EHRs and augment clinical decision support (CDS). Materials and Methods The National Institutes of Health (NIH)-sponsored Clinical Sequencing Exploratory Research and Electronic Medical Records & Genomics EHR Working Groups conducted a multiphase, iterative process involving working group discussions and 2 surveys in order to determine how genetic and genomic information are currently displayed in EHRs, envision optimal uses for different types of genetic or genomic information, and prioritize areas for EHR improvement. Results There is substantial heterogeneity in how genetic information enters and is documented in EHR systems. Most institutions indicated that genetic information was displayed in multiple locations in their EHRs. Among surveyed institutions, genetic information enters the EHR through multiple laboratory sources and through clinician notes. For laboratory-based data, the source laboratory was the main determinant of the location of genetic information in the EHR. The highest priority recommendation was to address the need to implement CDS mechanisms and content for decision support for medically actionable genetic information. Conclusion Heterogeneity of genetic information flow and importance of source laboratory, rather than clinical content, as a determinant of information representation are major barriers to using genetic information optimally in patient care. Greater effort to develop interoperable systems to receive and consistently display genetic and/or genomic information and alert clinicians to genomic-dependent improvements to clinical care is recommended.

Objective To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node ( RPLN ) recurrence of renal cell carcinoma ( RCC ) using a multicentre international cohort. Patients and Methods In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pT any N any M0 disease. Progression‐free ( PFS ) and cancer‐specific survival ( CSS ) were estimated using the Kaplan–Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression. Results The median (interquartile range, IQR ) age at resection was 57.0 (50.0–62.5) years. The median ( IQR ) time to RPLN recurrence after nephrectomy was 12.6 (6.9–39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5–24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7–44.2] months) ( P = 0.66). The median ( IQR ) size of the RPLN recurrence before resection was 2.6 (1.9–5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median ( IQR ) follow‐up after RPLN resection for patients alive at last follow‐up was 28.0 (13.7–51.2) months. During follow‐up, 26 patients developed RCC recurrence, at a median ( IQR ) of 9.9 (4.0–18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3‐ and 5‐year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005). Conclusion Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance.