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BackgroundOral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non–vitamin K antagonist oral anticoagulants (NOACs) have not been characterized.HypothesisAnticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation.MethodsUsing the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status.ResultsAmong 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow‐up of 30 months (interquartile range, 24–36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65–77.5 years] vs 77 years [range, 70–82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7–99.0] vs 65.8 [range, 50.0–91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty‐day periprocedure bleeding and stroke adverse events were infrequent.ConclusionsManagement of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin‐ and NOAC‐treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC‐treated patients.

AbstractBackgroundWearable technology is growing in popularity as a result of its ability to interface with normal human movement and function.MethodsUsing proprietary hardware and software, neuronavigation images were captured and transferred wirelessly via a password‐encrypted network to the head‐up display. The operating surgeon wore a loupe‐mounted wearable head‐up display during image‐guided parieto‐occipital ventriculoperitoneal shunt placement in two patients.ResultsThe shunt placement was completed successfully without complications. The tip of the catheter ended well within the ventricles away from the ventricular wall. The wearable device allowed for continuous monitoring of neuronavigation images in the right upper corner of the surgeon's visual field without the need for the surgeon to turn his head to view the monitors.ConclusionsThe adaptable nature of this proposed system permits the display of video data to the operating surgeon without diverting attention away from the operative task. This technology has the potential to enhance image‐guided procedures.

AbstractMedical devices increasingly depend on software. While this expands the ability of devices to perform key therapeutic and diagnostic functions, reliance on software inevitably causes exposure to hazards of security vulnerabilities. This article uses a recent high‐profile case example to outline a proactive approach to security awareness that incorporates a scientific, risk‐based analysis of security concerns that supports ongoing discussions with patients about their medical devices.

AbstractAfter decades on the margins of primary health care, surgical and anaesthesia care is gaining increasing priority within the global development arena. The 2015 publications of the Disease Control Priorities third edition on Essential Surgery and the Lancet Commission on Global Surgery created a compelling evidenced‐based argument for the fundamental role of surgery and anaesthesia within cost‐effective health systems strengthening global strategy. The launch of the Global Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has further coordinated efforts to build priority for surgical care and anaesthesia. These combined efforts culminated in the approval of a World Health Assembly resolution recognizing the role of surgical care and anaesthesia as part of universal health coverage. Momentum gained from these milestones highlights the need to identify consensus goals, targets and indicators to guide policy implementation and track progress at the national level. Through an open consultative process that incorporated input from stakeholders from around the globe, a global target calling for safe surgical and anaesthesia care for 80% of the world by 2030 was proposed. In order to achieve this target, we also propose 15 consensus indicators that build on existing surgical systems metrics and expand the ability to prioritize surgical systems strengthening around the world.

Purpose To evaluate the minimum 2‐year postoperative clinical outcomes and the rate of return to sports in athletes who underwent capsular plication for the treatment of ligamentous laxity and/or borderline dysplasia during hip arthroscopy for the treatment of femoroacetabular impingement and labral pathology. Methods Since 2008, data were prospectively collected on patients who underwent hip arthroscopy for the treatment of femoroacetabular impingement and/or labral tears. Inclusion criteria were as follows: athlete at the high school, collegiate, or professional levels preoperatively, underwent capsular plication, and preoperatively recorded patient‐reported outcome scores including modified Harris hip score (mHHS), nonarthritic athletic hip score (NAHS), hip outcome score—sports‐specific subscale (HOS‐SSS), and visual analog scale (VAS). Exclusion criteria were as follows: <16 years old, preoperative Tönnis grade >1, and previous hip conditions. Sports activity and competitive levels were collected at a minimum of 2 years postoperatively. Results Fifty‐one hips (49 patients) met the inclusion criteria, and 41 hips (39 patients) had minimum 2‐year follow‐up (80.4% follow‐up). Mean mHHS increased from 67.1 preoperatively to 83.5 ( P < .0001). Mean NAHS increased from 66.8 to 88.8 ( P < .0001). Mean HOS‐SSS improved from 46.8 to 80.1 ( P < .0001). Mean VAS decreased from 5.1 to 1.7 ( P < .0001). Thirty‐five (85.4%) hip arthroscopies allowed the patients to return to sports at follow‐up. Thirty‐four (82.9%) hip arthroscopies allowed the patients to maintain their competitive physical abilities at follow‐up. Conclusions Patient‐reported outcomes and VAS in athletes significantly improved at a minimum of 2 years after capsular plication as a part of hip arthroscopy addressing varying pathologies. In addition, most patients returned to sports at similar or higher competitive levels. These results suggest that capsular plication is a favorable treatment option in athletes with ligamentous laxity and/or borderline dysplasia. Level of Evidence Level IV, therapeutic case series.

Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 (non-V600 BRAF mutations). Methods We conducted this multicenter, retrospective cohort study to characterize the clinical, pathologic, and survival implications of non-V600 BRAF mutations in metastatic CRC. We pooled patients in whom non-V600 BRAF mutations were identified from NGS databases at three large molecular genetics reference laboratories. Results A total of 9,643 patients with metastatic CRC underwent NGS testing. We identified 208 patients with non-V600 BRAF mutations, which occurred in 2.2% of all patients tested and accounted for 22% of all BRAF mutations identified. Cancers with non-V600 BRAF mutations, compared with cancers with V600E BRAF (V600E BRAF) mutations, were found in patients who were significantly younger (58 v 68 years, respectively), fewer female patients (46% v 65%, respectively), and patients who had fewer high-grade tumors (13% v 64%, respectively) or right-sided primary tumors (36% v 81%, respectively). Median overall survival was significantly longer in patients with non-V600 BRAF-mutant metastatic CRC compared with those with both V600E BRAF-mutant and wild-type BRAF metastatic CRC (60.7 v 11.4 v 43.0 months, respectively; P < .001). In multivariable analysis, non-V600 BRAF mutation was independently associated with improved overall survival (hazard ratio, 0.18; P < .001). Conclusion Non-V600 BRAF mutations occur in approximately 2.2% of patients with metastatic CRC and define a clinically distinct subtype of CRC with an excellent prognosis.

Abstract Objectives To develop and evaluate a real-time methylation-specific polymerase chain reaction (RT-MSP) MGMT assay, with a particular focus on small biopsies and indeterminate testing results. Methods We assessed formalin-fixed paraffin-embedded glioblastoma or gliosarcoma specimens (n = 641). A test-validation group (n = 51) with previously obtained reference laboratory (RL) results was used to determine performance characteristics of the RT-MSP assay. An indeterminate (equivocal) category was established for cases that could not be clearly classified as positive or negative. Results Overall agreement of RT-MSP and RL results was 91% (41/45 nonindeterminate cases). Discordant cases were tested by pyrosequencing, and results were most concordant with RT-MSP. Among cases with limited amounts of tissue (n = 7), six yielded valid results by RT-MSP (all negative); the single invalid result consisted of a stereotactic biopsy specimen obtained 14 years prior. A subset of indeterminate cases obtained during clinical testing (n = 18/575 [3%]) was also evaluated by pyrosequencing and showed a heterogeneous pattern of methylation across the eight interrogated CpG sites. Conclusions The RT-MSP assay that we developed in-house is a robust clinical detection method for the heterogeneous process of MGMT promoter methylation in glioblastoma.

Linked ContentThis article is linked to Mahadev et al and Braude, Newnham papers. To view these articles visit https://doi.org/10.1111/apt.13988 and https://doi.org/10.1111/apt.14055.

ABSTRACT Objectives: The aim of the study was to describe changes in intestinal permeability in early childhood in diverse epidemiologic settings. Methods: In a birth cohort study, the lactulose:mannitol (L:M) test was administered to 1980 children at 4 time points in the first 24 months of life in 8 countries. Data from the Brazil site with an incidence of diarrhea similar to that seen in the United States and no growth faltering was used as an internal study reference to derive age‐ and sex‐specific z scores for mannitol and lactulose recoveries and the L:M ratio. Results: A total of 6602 tests demonstrated mannitol recovery, lactulose recovery, and the L:M ratio were associated with country, sex, and age. There was heterogeneity in the recovery of both probes between sites with mean mannitol recovery ranging for 1.34% to 5.88%, lactulose recovery of 0.19% to 0.58%, and L:M ratios 0.10 to 0.17 in boys of 3 months of age across different sites. We observed strong sex‐specific differences in both mannitol and lactulose recovery, with boys having higher recovery of both probes. Alterations in intestinal barrier function increased in most sites from 3 to 9 months of age and plateaued or diminished from 9 to 15 months of age. Conclusions: Alterations in recovery of the probes differ markedly in different epidemiologic contexts in children living in the developing world. The rate of change in the L:M‐ z ratio was most rapid and consistently disparate from the reference standard in the period between 6 and 9 months of age, suggesting that this is a critical period of physiologic impact of enteropathy in these populations.

Background Patients with celiac disease (CD) are at increased risk of certain infections, but it is unknown if mucosal healing influences this risk. Methods We collected data on 29,096 individuals with CD (equal to villous atrophy) through Sweden’s 28 pathology departments undergoing biopsy 1969–2008. Through the Swedish Patient Register we obtained information on any infection and specifically sepsis, streptococcal infection, influenza, Clostridium difficile, herpes zoster and pneumococcal infection up until December 2009. We used Cox regression to calculate hazard ratios (HRs) for the risk of future diagnosis of infection according to mucosal healing on follow-up biopsy (persistent villous atrophy vs mucosal healing). Results Of 5598 CD individuals with no record of any infections before follow-up biopsy, 45% had persistent villous atrophy, 619 (24%) of them had a later infection, compared to 579 (19%) in those with mucosal healing ( p < 0.01); the yearly incidence was 2.1% in both groups. Adjusting for age, sex, calendar period, time between biopsies and education, persistent villous atrophy was however not associated with later infection overall (HR = 0.99; 95% CI = 0.88–1.11) or with any of the specific infections. Conclusions In CD, mucosal healing does not influence the risk of serious infection requiring hospital-based medical attention.