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Background: Left atrial appendage occlusion (LAAO) is increasingly used as an alternative to oral anticoagulation for stroke prevention in select patients with atrial fibrillation. Data on outcomes in racial and ethnic minority individuals are limited. This analysis assessed differences in the use and outcomes of LAAO by race and ethnicity in a large national registry., Methods and Results: This analysis acquired data on patients who underwent WATCHMAN FLX implantation from the retrospective NCDR (National Cardiovascular Data Registry) LAAO registry through September 2022. All patients with an attempted WATCHMAN FLX implantation and known race and ethnicity were included. Baseline characteristics and 1-year event rates were compared. A total of 97 185 patients were analyzed; 87 339 were White individuals (90%), 3750 Black individuals (3.9%), and 2866 Hispanic individuals (Hispanic/Latinx), 2.9%). Black and Hispanic patients were younger, with a higher incidence of prior stroke and significant bleeding compared with White patients. Black and Hispanic patients were treated with LAAO in smaller numbers relative to their proportion of the US population. Rates of procedural success were similar between groups. Though direct oral anticoagulants were prescribed in most patients across the groups, dual and single antiplatelet therapy were prescribed more often in Black patients. Black patients had significantly higher rates of 1-year death and bleeding compared with White and Hispanic patients., Conclusions: Patients from racial and ethnic minority groups comprise a disproportionately small fraction of all patients who undergo LAAO. Black and Hispanic patients were younger but had significantly higher comorbidities compared with White patients. Procedural success was similar among the groups, but Black patients experienced higher rates of death and bleeding at 1 year.

Background: Oral anticoagulation is recommended after ablation for atrial fibrillation among patients at high risk for stroke. Left atrial appendage closure is a mechanical alternative to anticoagulation, but data regarding its use after atrial fibrillation ablation are lacking., Methods: We conducted an international randomized trial involving 1600 patients with atrial fibrillation who had an elevated score (≥2 in men and ≥3 in women) on the CHA 2 DS 2 -VASc scale (range, 0 to 9, with higher scores indicating a greater risk of stroke) and who underwent catheter ablation. Patients were randomly assigned in a 1:1 ratio to undergo left atrial appendage closure or receive oral anticoagulation. The primary safety end point, tested for superiority, was non-procedure-related major bleeding or clinically relevant nonmajor bleeding. The primary efficacy end point, tested for noninferiority, was a composite of death from any cause, stroke, or systemic embolism at 36 months. The secondary end point, tested for noninferiority, was major bleeding, including procedure-related bleeding, through 36 months., Results: A total of 803 patients were assigned to undergo left atrial appendage closure, and 797 to receive anticoagulant therapy. The mean (±SD) age of the patients was 69.6±7.7 years, 34.1% of the patients were women, and the mean CHA 2 DS 2 -VASc score was 3.5±1.3. At 36 months, a primary safety end-point event had occurred in 65 patients (8.5%) in the left atrial appendage closure group (device group) and in 137 patients (18.1%) in the anticoagulation group (P<0.001 for superiority); a primary efficacy end-point event had occurred in 41 patients (5.3%) and 44 patients (5.8%), respectively (P<0.001 for noninferiority); and a secondary end-point event had occurred in 3.9% and 5.0% (P<0.001 for noninferiority). Complications related to the appendage closure device or procedure occurred in 23 patients., Conclusions: Among patients who underwent catheter-based atrial fibrillation ablation, left atrial appendage closure was associated with a lower risk of non-procedure-related major or clinically relevant nonmajor bleeding than oral anticoagulation and was noninferior to oral anticoagulation with respect to a composite of death from any cause, stroke, or systemic embolism at 36 months. (Funded by Boston Scientific; OPTION ClinicalTrials.gov number, NCT03795298.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Long-term outcomes following left atrial appendage occlusion outside clinical trials and small registries are largely unknown. Collecting these data was a condition of US market authorization of the WATCHMAN device. The aim of this analysis was to evaluate the rates of stroke, bleeding, and death among Medicare beneficiaries following left atrial appendage occlusion implantation during initial commercial availability of the WATCHMAN left atrial appendage occlusion device overall and in important subgroups., Methods: All Medicare fee-for-service beneficiaries ≥65 years of age who underwent left atrial appendage occlusion from April 1, 2016, to August 31, 2020, were included based on the International Classification of Diseases, Tenth Revision , and Current Procedural Terminology codes. Over a 5-year follow-up period, the cumulative incidence over time of mortality, ischemic stroke, and major bleeding were calculated using the International Classification of Diseases, Tenth Revision , diagnosis codes for the full study cohort and within important prespecified subgroups., Results: WATCHMAN recipients (n=48 763) were a median of 77 (interquartile range, 72-82) years of age, 42% female, and mostly White (93%). The median CHA 2 DS 2 VASc score was 4 (interquartile range, 3-5) with prior major bleeding in 42% and prior stroke in 12%. At 5 years, death occurred in 44%, bleeding in 15% (with higher risk early following implantation), and ischemic stroke in 7%. Each of these end points was more common with greater baseline age. Male patients had greater 5-year mortality than female patients (46.9% versus 40.6%), but there was no difference between sexes in the rates of ischemic stroke (6.6% versus 7.5%) or major bleeding (14.9% for both). WATCHMAN recipients with prior ischemic stroke or a major bleeding event were older and frailer; these groups had higher rates of ischemic stroke, major bleeding, and death., Conclusions: Compared with patients enrolled in the pivotal clinical trials, Medicare beneficiaries undergoing WATCHMAN implantation were older, more female, and had more comorbid conditions. Substantial long-term mortality and major bleeding following WATCHMAN reflect the high-risk nature of the patient population, while the ischemic stroke rate was relatively low (<1.5% per year)., Competing Interests: Dr Zeitler reports consulting and speaking fees for Abbott, Biosense Webster, Medtronic, and Sanofi; travel support from Abbott, Biosense Webster, and Medtronic; and research support from Biosense Webster, Sanofi, and the National Institutes of Health. B. Bian, B.G., Dr Allocco, Dr Christen, and Dr Roy were full-time employees of Boston Scientific Corporation at the time of this work. Dr Cohen reports research grant support (to institution) from Boston Scientific, Abbott, Edwards Lifesciences, Philips, CathWorks, I-Rhythm, and Zoll Medical and consulting income from Boston Scientific, Abbott, Edwards Lifesciences, Medtronic, Elixir Medical, and HeartBeam. The other authors report no conflicts.

Dynamic susceptibility contrast (DSC) MRI is commonly part of brain tumor imaging. For quantitative analysis, measurement of the arterial input function and tissue concentration time curve is required. Usually, a linear relationship between the MR signal changes and contrast agent concentration ([Gd]) is assumed, even though this is a known simplification. The aim of this study was to develop a realistic 3D simulation model as an efficient method to assess the relationship between ΔR 2 (*) versus [Gd]. The results were validated against previously obtained 2D data and in vitro data. Furthermore, hematocrit levels (30%-50%) and field strengths (1.5-3.0-7.0 T) were varied. Subsequently, realistic tumor vascular networks were derived from intraoperative high framerate Doppler ultrasound data to study the influence of vascular structure and orientation with respect to the main magnetic field (1.5-3.0-7.0 T) for the calculation of ΔR 2 (*) versus [Gd]. The results were validated against previously obtained 2D data and in vitro data. Furthermore, hematocrit levels (30%-50%) and field strengths (1.5-3.0-7.0 T) were varied. Subsequently, realistic tumor vascular networks were derived from intraoperative high framerate Doppler ultrasound data to study the influence of vascular structure and orientation with respect to the main magnetic field (1.5-3.0-7.0 T) for the calculation of ΔR 2 (*) versus [Gd] in brain tissue. For whole blood, good agreement of the 3D model was found with in vitro and 2D simulation data when red blood cells were aligned with the blood flow. For brain tissue, minor differences were found between the vascular networks. The effect of vessel direction with respect to B 0 was apparent in case of clear directionality of the main vessels. The dependency on field strength agreed with previous reports. In conclusion, we have shown that the relationship between ΔR 2 (*) and [Gd] is affected by the organization of red blood cells and orientation of blood vessels with respect to the main magnetic field, as well as the field strength. These findings are important for further optimization of the realistic 3D model that could eventually be used to improve the estimation of hemodynamic parameters from DSC-MRI., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Background: The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described., Objectives: This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens., Methods: The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022. They grouped patients by mutually exclusive discharge antithrombotic strategies and compared the rates of adverse events at 45 days and 6 months using multivariable Cox proportional hazards regression., Results: Among 53,878 patients undergoing successful LAAO with the second-generation LAA closure device, the most common antithrombotic discharge regimens were direct oral anticoagulant (DOAC) plus aspirin (48.3%), DOAC alone (22.6%), dual antiplatelet therapy (8.1%), warfarin plus aspirin (7.7%), and DOAC plus P2Y 12 inhibitor (4.9%). In multivariate analysis, DOAC alone had a lower rate of major adverse events and major bleeding at 45 days of follow-up compared with DOAC plus aspirin (major adverse events: HR: 0.78; 95% CI: 0.68-0.91; major bleeding: HR: 0.69; 95% CI: 0.60-0.80). These differences persisted at 6 months. Warfarin without aspirin also showed lower rates of major bleeding at both time points. No differences were seen in stroke/transient ischemic attack or device-related thrombus., Conclusions: In real-world U.S. practice, discharge on DOAC alone or warfarin alone was associated with a lower rate of adverse events compared with DOAC plus aspirin., Competing Interests: Funding Support and Author Disclosures This analysis was supported by the Boston Scientific Corporation. Although Boston Scientific had no role in the data collection, development of study questions, or analytic approaches, it paid for the statistical analytical work and manuscript support. No authors were compensated for their work on this study. The views expressed here represent those of the authors, and do not necessarily represent the official views of the American College of Cardiology Foundation’s National Cardiovascular Data Registry or its associated professional societies identified at CVQuality.ACC.org/NCDR. Dr Hsu has received honoraria from Medtronic, Abbott, Boston Scientific, Biotronik, Janssen Pharmaceuticals, Bristol Myers Squibb, Pfizer, Sanofi, Zoll Medical, iRhythm, Acutus Medical, Galvanize Therapeutics, and Biosense Webster; has received research grants from Biotronik and Biosense Webster; and has equity in Vektor Medical. Dr Yeh has received research funding and consulting fees from Abbott Vascular, Boston Scientific, and Medtronic; and has received research funding from Bard, Cook, and Philips. Dr Price has received consulting honoraria, speaker fees, and proctoring fees from Abbott Vascular and Boston Scientific; has received consulting honoraria and speaker fees from Medtronic, W.L. Gore, Philips, and Shockwave; and has equity in Indian Wells, Inc. Dr Piccini is supported by grant R01AG074185 from the National Institutes of Aging; receives grants for clinical research from Abbott, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, iRhythm, and Philips; and serves as a consultant to Abbott, Abbvie, ARCA biopharma, Bayer, Boston Scientific, Bristol Myers Squibb (Myokardia), Element Science, Itamar Medical, LivaNova, Medtronic, Milestone, ElectroPhysiology Frontiers, ReCor, Sanofi, Philips, and Up-to-Date. Drs Christen and Allocco are full-time employees and stockholders of Boston Scientific. Dr Freeman has received research funding from the National Institutes of Health/National Heart, Lung, and Blood Institute, and the American College of Cardiology National Cardiovascular Data Registry; has received consulting/advisory board fees from Medtronic, Boston Scientific, Biosense Webster, and PaceMate; and has equity in PaceMate. All other authors have reported that they have no relationships relevant to the contents of this paper., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: PINNACLE FLX (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the WATCHMAN FLX LAA Closure Technology) demonstrated improved outcomes and low incidence of adverse events with the WATCHMAN FLX device in a controlled setting. The National Cardiovascular Disease Registry's Left Atrial Appendage Occlusion Registry was utilized to assess the safety and effectiveness of WATCHMAN FLX in contemporary clinical practice in the United States., Methods: The WATCHMAN FLX Device Surveillance Post Approval Analysis Plan used data from the Left Atrial Appendage Occlusion registry to identify patients undergoing WATCHMAN FLX implantation between August 2020 and September 2022. The key safety end point was defined as all-cause death, ischemic stroke, systemic embolism, or device or procedure-related events requiring open cardiac surgery or major endovascular intervention between device implantation and hospital discharge. Major adverse events were reported at hospital discharge, 45 days, and 1 year., Results: Among 97 185 patients in the Left Atrial Appendage Occlusion registry undergoing WATCHMAN FLX, successful implantation occurred in 97.5% (n=94 784) of patients. The key safety end point occurred in 0.45% of patients. At 45 days post-procedure, all-cause death occurred in 0.81% patients, ischemic stroke in 0.23%, major bleeding in 3.1%, pericardial effusion requiring intervention in 0.50%, device-related thrombus in 0.44%, and device embolism in 0.04% patients. No peri-device leak was observed in 83.1% of patients at 45 days. At 1 year, the rate of all-cause death was 8.2%, the rate of any stroke was 1.5% (ischemic stroke, 1.2%), and major bleeding occurred in 6.4% of patients., Conclusions: In a large contemporary cohort of patients with the WATCHMAN FLX device, the rates of implant success and clinical outcomes through 1 year were comparable with the PINNACLE FLX study, demonstrating that favorable outcomes achieved in the pivotal approval study can be replicated in routine clinical practice., Competing Interests: Dr R.W. Yeh is a consultant and has research grants with Boston Scientific Corporation. Dr J.P. Piccini is a consultant and has research grants with Abbott, Boston Scientific Corporation and Bayer. Drs T. Christen and D.J. Allocco are full time employees and stockholders in Boston Scientific Corporation. The other authors report no conflicts.

Vascularized bone grafts of the wrist and hand help to achieve bone union in various clinical settings such as bone fusion or nonunion treatment. Among the multiple possible donor sites, the base of the second metacarpal is convenient because of its relatively straightforward harvesting, lack of impairment of the hand vascularization, sufficient bone supply for small joint fusion and phalanx or metacarpal nonunion management. The flap is versatile as it can reach any carpal and metacarpal bone as well as the proximal phalanx of all fingers. The arc of rotation of the flap depends on which side of the dorsal intercarpal arch it is based, either radially or ulnarly. It can also be pedicled distally by a retrograde flow through the second dorsal metacarpal artery. The robust vascularization of the flap allows for reliable healing. We present five new indications in various clinical settings that illustrate the versatility of the arc of rotation of the flap.

Background: The original description of boxer's knuckle injury of the fifth ray mentions that the injury occurs between the extensor digitorum communis (EDC) and the extensor digiti minimi (EDM). Subsequent reports claim similar findings. Anatomical studies show that the EDC of the fifth ray is absent in most patients, while the EDM is generally composed of two slips. We present a modification of the current description of boxer's knuckle injury of the little finger based on the correlation between advanced preoperative 3D imaging and intraoperative findings., Methods: Five patients were investigated preoperatively using high-resolution ultrasound and 3D tendon reconstruction-based MR arthrography. Surgical exploration identified the lesion site relative to the EDM and EDC., Results: All patients had two slips of the EDM and no EDC to the fifth ray. The injury appeared as a longitudinal tear of the EDM between its two slips. The mean gap was 7.8 mm (range 4.5-10 mm) on the pathological side vs. 1.3 mm (range 1-2 mm) on the healthy contralateral side., Conclusions: We believe that previous descriptions of boxer's knuckle of the fifth ray are inaccurate. High-resolution ultrasound and 3D reconstructions based on MR arthrography are reliable diagnostic tools allowing to locate the injury with precision.

Background: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy., Study Design: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding., Conclusions: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF., Clinical Trial Registration: NCT04394546., Competing Interests: Disclosures Dr Kar is a consultant to BSC, Abbott Vascular, Medtronic, LAMINAR, V-wave, Intershunt Highlife, co-principal investigator of the CHAMPION AF and REPAIR-MR studies and a steering committee member for the Triluminate and RELIEVE HF trials. Dr Doshi serves as a consultant to BSC, Biosense Webster, Abbott Vascular, Conformal and is co-principal investigator of the CHAMPION AF study. Dr Alkhouli is on the advisory board for BSC and received institutional research grant from BSC. Dr Camm received personal fees from Anthos, Menarini, Bayer, Daiichi Sankyo, Pfizer, Abbott and BSC. Dr Coylewright received research funding from BSC and Edwards Life Sciences and is a consultant for BSC, Edwards Life Sciences, Occlutech and Medtronic. Dr Gibson received research grant support payable to his institution and consulting fees from J&J, BMS, Diachi Sankyo, CeleCor and Merck. Dr Granger receives consulting fees from Abbvie, Abiomed, Alnylam Pharmaceuticals, Anthos, Bayer Corporation, Boehringer Ingelheim, BSC, Bristol Myers Squibb, Cardionomics, CeleCor Therapeutics, Janssen Pharmaceutical, Medscape, LLC, Medtronic, Inc., Merck, Nation Institutes of Health, Novo Nordisk, Novartis Pharmaceutical Company, PLX Pharma, Pfizer, Philips, REATA and NephroSynergy. He has an equity in Tenac.io. and salary funded by Duke grants sponsored by Boehinger Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, FDA, Janssen Pharmaceuticals, Novartis Pharmaceutical Company, Pfizer, and Philips. Dr Gurol received research funding from NIH and the hospital he is affiliated to received research funding from AVID, Pfizer and BSC. Dr Huber is on the Watchman Advisory Board. Dr Mansour is a consultant: for BSC. Dr Nair is an advisory board member and consultant for, and received research grant support from Biosense Webster, BSC, Abbott and Medtronic. Dr Natale is a consultant for Abbott, Baylis, Biosense Webster, BSC, Biotronik and Medtronic. Dr Pocock is a consultant for BSC. Dr Reddy serves as a consultant to, and has received grant support from, BSC. He reports additional disclosures unrelated to this manuscript: Consultant for and has equity in Ablacon, Acutus Medical, Affera, Medtronic, Apama Medical, Anumana, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD, Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Farapulse, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; Consultant for AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, Pulse Biosciences; Equity in Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. Dr Saliba is on the advisory board for BSC. Dr Christen and Allocco are full-time employees with an equity interest in BSC. Dr Ellenbogen received research support/lecture fees/honorarium and is a consultant for BSC. Dr Leon received clinical research grants to Columbia University from Abiomed-J&J, Abbott, BSC, Edwards and Medtronic., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

ImUnity is an original 2.5D deep-learning model designed for efficient and flexible MR image harmonization. A VAE-GAN network, coupled with a confusion module and an optional biological preservation module, uses multiple 2D slices taken from different anatomical locations in each subject of the training database, as well as image contrast transformations for its training. It eventually generates 'corrected' MR images that can be used for various multi-center population studies. Using 3 open source databases (ABIDE, OASIS and SRPBS), which contain MR images from multiple acquisition scanner types or vendors and a large range of subjects ages, we show that ImUnity: (1) outperforms state-of-the-art methods in terms of quality of images generated using traveling subjects; (2) removes sites or scanner biases while improving patients classification; (3) harmonizes data coming from new sites or scanners without the need for an additional fine-tuning and (4) allows the selection of multiple MR reconstructed images according to the desired applications. Tested here on T1-weighted images, ImUnity could be used to harmonize other types of medical images., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Aims: Leptin has been associated with adverse effects on cardiovascular disease, but the effect of confounding by body fat in these associations remains unclear. To investigate associations between leptin and heart function and subclinical cardiovascular disease adjusted for total body fat, and to investigate the causal relation between leptin and cardiovascular disease using Mendelian randomisation., Methods and Results: Leptin concentrations, total body fat and diverse measures of subclinical cardiovascular disease were determined in participants of the Netherlands Epidemiology of Obesity study. Linear regression between leptin concentration and measures of heart function, ECG measures, and carotid intima media thickness as a measure of subclinical atherosclerosis was adjusted for potential confounding factors, and additionally including total body fat. We analysed the combined effects of genetic variants from a GWAS on leptin concentrations in publicly-available summary statistics of coronary heart disease GWAS (CARDIoGRAMplusC4D, n = 184,305). As many as 6107 men and women, mean (SD) age 56 (6) years, BMI 26 (4) kg/m 2 , and median leptin concentration 12.1 μg (IQR: 6.7-22.6) were included. In observational analyses, leptin was weakly associated with heart function and subclinical cardiovascular disease, but these associations attenuated when adjusting for total body fat. A doubling of genetically-determined leptin concentration was associated with an odds ratio of cardiovascular disease of 0.69 (0.37, 1.27)., Conclusion: Observational associations between leptin and subclinical measures of cardiovascular disease were largely explained by differences in total body fat. Results of analyses of genetically-determined leptin and coronary heart disease risk were inconclusive due to a large confidence interval., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The FLXibility Post-Approval Study collected data on unselected patients implanted with a WATCHMAN FLX in a commercial clinical setting., Methods and Results: Patients were implanted with a WATCHMAN FLX per local standard of care, with a subsequent first follow-up visit from 45 to 120 days post-implant and a final follow-up at 1-year post-procedure. A Clinical Event Committee adjudicated all major adverse events and TEE/CT imaging results were adjudicated by a core laboratory. Among 300 patients enrolled at 17 centres in Europe, the mean age was 74.6 ± 8.0 years, mean CHA2DS2-VASc score was 4.3 ± 1.6, and 62.1% were male. The device was successfully implanted in 99.0% (297/300) of patients. The post-implant medication regimen was DAPT for 87.3% (262/300). At first follow-up, core-lab adjudicated complete seal was 88.2% (149/169), 9.5% (16/169) had leak <3 mm, 2.4 (4/169) had leak ≥3 mm to ≤5 mm, and 0% had >5 mm leak. At 1 year, 93.3% (280/300) had final follow-up; 60.5% of patients were on a single antiplatelet medication, 21.4% were on DAPT, 5.6% were on direct oral anticoagulation, and 12.1% were not taking any antiplatelet/anticoagulation medication. Adverse event rates through 1 year were: all-cause death 10.8% (32/295); CV/unexplained death 5.1% (15/295); disabling and non-disabling stroke each 1.0% (3/295, all non-fatal); pericardial effusion requiring surgery or pericardiocentesis 1.0% (3/295); and device-related thrombus 2.4% (7/295)., Conclusion: The WATCHMAN FLX device had excellent procedural success rates, high LAA seal rates, and low rates of thromboembolic events in everyday clinical practice., Competing Interests: Conflict of interest. T.R.B.: proctoring/consultancy honoraria (Boston Scientific). M.G.: proctoring/consultancy honoraria (Abbott, Boston Scientific), research grants (Boston Scientific). J.E.N.K.: procotoring/consultancy honoraria (Abbott, Boston Scientific), research grants (Abbott, Boston Scientific). T.S.: proctoring/consultancy honoraria (Boston Scientific). M.S.: nothing to disclose. G.C.: proctoring/consultancy honoraria (Abbott, Boston Scientific, Lifetech). M.B.: Speaker honoraria and study support (Abbott, Boston Scientific, Daiichi, Medtronic, MSD/Pfizer). D.H.-S.: proctoring/advisory board honoraria (Abbott, Boston Scientific, Eclipse Medical). T.C.: salary and equity (Boston Scientific Corporation). D.J.A.: salary and equity (Boston Scientific Corporation)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Intracardiac echocardiography (ICE) is increasingly used to guide left atrial appendage closure (LAAC)., Objectives: The aim of this study was to investigate the efficacy and safety of ICE-guided LAAC with the Watchman FLX device., Methods: The ICE LAA (I Can See Left Atrial Appendage) study was a prospective, multicenter study with independent adjudication of echocardiographic data by a core laboratory and clinical events by a clinical events committee. Patients with atrial fibrillation with CHA 2 DS 2 -VASc scores ≥2 and clinical indications for LAAC were eligible. Preplanning with either cardiac computed tomography or transesophageal echocardiography (TEE) within 7 days prior to LAAC was mandatory. Intraprocedural ICE was carried out from the left atrium. The primary outcome was the rate of significant peridevice leaks (>5 mm) at 45-day TEE., Results: A total of 100 patients were enrolled. The mean age was 76 ± 8 years, the mean CHA 2 DS 2 -VASc score was 4.0 ± 1.5, and the mean HAS-BLED score was 2.5 ± 0.9. The incidence of the primary outcome of significant peridevice leak (>5 mm) was 0%; all patients evaluated by TEE at 45 days had effective LAAC. All patients received Watchman FLX devices, and technical success was 100%. The number of devices per case was 1.0 ± 0.1. ICE successfully guided the assessment of device release criteria, including device compression (19.2% ± 7.1%; recommended range: 10%-30%). No subject required conversion to TEE. Procedural complications were 4 access-site bleeds. There was no stroke, transient ischemic attack, systemic embolization, pericardial effusion, device embolization, or device-related thrombus during the procedure or 45-day follow-up., Conclusions: ICE can be used to successfully guide LAAC with the Watchman FLX, with excellent procedural success, a high rate of effective LAAC, and minimal periprocedural complications. (I Can See Left Atrial Appendage [ICELAA] Clinical Study; NCT04196335)., Competing Interests: Funding Support and Author Disclosures The ICE LAA study was supported by Boston Scientific. Dr Nielsen-Kudsk is a proctor and an investigator for Abbott and Boston Scientific. Dr Berti is a proctor for Abbott and Boston Scientific. Dr Caprioglio has received speaker honoraria from Abbott, Philips, and GE Healthcare. Dr Ronco has received speaker honoraria from Abbott and GE Healthcare. Dr Arzamendi is a proctor for Abbott and Boston Scientific. Dr Betts is a proctor for Boston Scientific. Dr Tondo is a proctor for Abbott and Boston Scientific. Drs Christen and Allocco are full-time employees of and stockholders in Boston Scientific., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background The PINNACLE FLX (Protection Against Embolism for Non-valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next-generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2-year outcomes with this next-generation left atrial appendage closure device. Methods and Results Patients with nonvalvular atrial fibrillation with CHA 2 DS 2 -VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA 2 DS 2 -VASc, 4.2±1.5), the secondary efficacy end point of 2-year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1-sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two-year rates of adverse events were as follows: 9.3% all-cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device-related thrombi after 1 year. Conclusions The secondary end point of 2-year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next-generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.

Study Objective: We aimed to assess the analgesic and anxiolytic efficacy of distraction, a nonpharmacologic intervention provided by 3-dimensional (3D) virtual reality (VR) compared with that provided by 2-dimensional (2D) VR during minor emergency department (ED) procedures., Methods: This randomized controlled study conducted in the ED of a teaching hospital included patients aged more than or equal to 18 years undergoing minor procedures. The patients watched the same computer-generated VR world either in 3D in a head-mounted display (intervention) or in 2D on a laptop screen (control). Our main outcomes were pain and anxiety during the procedure, assessed on a 100-mm visual analog scale. Secondary outcomes included the impression of telepresence in the computer-generated world assessed using the Igroup Presence Questionnaire, and the prevalence and intensity of cybersickness measured on a 100-mm visual analog scale., Results: The final analysis included 117 patients. The differences in median procedural pain and anxiety levels between the 2D and 3D VR groups were not significant: -3 mm (95% confidence interval [CI] -14 to 8) and -4 mm (95% CI -15 to 3), respectively; the difference in telepresence was 2.0 point (95% CI 0 to 2.0), and the proportion difference of cybersickness was -4% (95% CI -22 to 14), with an intensity difference of -5 mm (95% CI -9 to 3)., Conclusion: During minor procedures in adult patients in the ED, distraction by viewing a 3D virtual world in a head-mounted VR display did not result in lower average levels of procedural pain and anxiety than that by 2D viewing on a screen despite a higher sense of telepresence. There were no significant differences in the prevalence and intensity of cybersickness between the 2 groups., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: The PROGRESS PVL registry evaluated transcatheter aortic valve implantation (TAVI) in patients treated with ACURATE neo , a supra-annular self-expanding bioprosthetic aortic valve., Background: While clinical outcomes with TAVI are comparable with those achieved with surgery, residual aortic regurgitation (AR) and paravalvular leak (PVL) are common complications. The ACURATE neo valve has a pericardial sealing skirt designed to minimize PVL., Methods: The primary endpoint was the rate of total AR over time, as assessed by a core echocardiographic laboratory. The study enrolled 500 patients (mean age: 81.8 ± 5.1 years; 61% female; mean baseline STS score: 6.0 ± 4.5%) from 22 centers in Europe and Canada; 498 patients were treated with ACURATE neo ., Results: The rate of ≥ moderate AR was 4.6% at discharge and 3.1% at 12 months; the rate of ≥ moderate PVL was 4.6% at discharge and 2.6% at 12 months. Paired analyses showed significant improvement in overall PVL between discharge and 12 months ( P < 0.001); 64.6% of patients had no change in PVL grade, 24.9% improved, and 10.5% worsened. Patients also exhibited significant improvement in transvalvular gradient ( P < 0.001) and effective orifice area ( P =0.01). The mortality rate was 2.2% at 30 days and 11.3% at 12 months. The permanent pacemaker implantation (PPI) rate was 10.2% at 30 days and 12.2% at 12 months., Conclusions: Results from PROGRESS PVL support the sustained safety and performance of TAVI with the ACURATE neo valve, showing excellent valve hemodynamics, good clinical outcomes, and significant interindividual improvement in PVL from discharge to 12-month follow-up., Competing Interests: Dr. Kim reports personal fees from Boston Scientific, Edwards Lifesciences, Abbott, Medtonic, and Meril, outside the submitted work. Dr. Thiele has nothing to disclose. Dr. Linke reports grants from Novartis and Edwards Lifesciences, personal fees from Medtronic, Abbott, Edwards Lifesciences, Boston Scientific, Astra Zeneca, Novartis, Pfizer, Abiomed, Bayer, and Boehringer, and other from Picardia, Transverse Medical, and Claret Medical, outside the submitted work. Dr. Kuntze reports grants from Edwards, outside the submitted work. Dr. Fichtlscherer has nothing to disclose. Dr. Webb reports personal fees from Edwards Lifesciences, outside the submitted work. Dr. Chu reports personal fees from Medtronic, Edwards Lifesciences, Boston Scientific, Abbott Vascular, Terumo Aortic, and Cryolife, outside the submitted work. Dr. Adam reports grants and personal fees from Medtronic and personal fees from Boston Scientific and Edwards Lifesciences, outside the submitted work. Dr Schymik has nothing to disclose. Dr. Geisler reports grants from Edwards Lifesciences and Medtronic, outside the submitted work. Dr. Kharbanda reports grants and personal fees from Boston Scientific, outside the submitted work. Drs. Christen and Allocco are employees and shareholders of Boston Scientific., (Copyright © 2022 Won-Keun Kim et al.)

Purpose: The walk ratio (WR)-the step-length/cadence relation-is a promising measure for gait control. GPS-running watches deliver clinically relevant outcomes including the WR. The aim of this study was to determine test-retest agreement, reliability and concurrent validity of an outdoor WR assessment using a GPS-running watch. Methods: Healthy adults and moderate-high functioning stroke survivors (≥6 months), performed the 1 km-outdoor walk twice using a GPS-running watch (Garmin Forerunner 35, GFR35) and a Step Activity Monitor (SAM 3). Global cognition was assessed using the Montreal Cognitive Assessment. Test-retest agreement and reliability were assessed using Bland-Altman plots, standard error of measurement (SEM), intraclass correlation coefficients (ICCs) and smallest detectable changes (SDCs). Concurrent validity was determined by the mean difference (MD), standard error (SE), mean absolute percentage errors (MAPEs) and Spearman's Rho between GFR35 and SAM3. WR values of the two groups were compared by a Welch's test. A hierarchical multiple regression was performed with the WR as dependent variable and possible predictors as independent variables. Results: Fifty-one healthy adults [median: 60.0 (47.0, 67.0) years) and 20 stroke survivors [mean: 63.1 (12.4) years, median: 76 (30, 146) months post-stroke] were included. Test-retest agreement and reliability were excellent (SEM% ≤ 2.2, ICCs > 0.9, SDC% ≤ 6.1) and concurrent validity was high (MAPE < 5, ρ > 0.7) for those walking ≥ 1 m/s. Walking < 1 m/s impaired accurate step counting and reduced agreement, reliability, and validity. The WR differed between healthy adults and stroke survivors (t = -2.126, p = 0.045). The hierarchical regression model including stroke and global cognition (Montreal Cognitive Assessment, 0-30) explained 25% of the WR variance (ΔR 2 = 0.246, p < 0.001). Stroke had no effect ( β = -0.05, p = 0.682), but global cognition was a predictor for an altered WR ( β = 0.44, p = 0.001). Discussion: The outdoor WR assessment using the GFR35 showed excellent test-retest agreement, reliability and concurrent validity in healthy adults and chronic stroke survivors walking at least 1 m/s. As the WR seems relevant in chronic stroke, future studies should further investigate this parameter., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with one of the authors JH at time of review., (Copyright © 2022 Huber, Knols, Held, Christen and de Bruin.)

The ischemic penumbra is defined as the severely hypoperfused, functionally impaired, at-risk but not yet infarcted tissue that will be progressively recruited into the infarct core. Early reperfusion aims to save the ischemic penumbra by preventing infarct core expansion and is the mainstay of acute ischemic stroke therapy. Intravenous thrombolysis and mechanical thrombectomy for selected patients with large vessel occlusion has been shown to improve functional outcome. Given the varying speed of infarct core progression among individuals, a therapeutic window tailored to each patient has recently been proposed. Recent studies have demonstrated that reperfusion therapies are beneficial in patients with a persistent ischemic penumbra, beyond conventional time windows. As a result, mapping the penumbra has become crucial in emergency settings for guiding personalized therapy. The penumbra was first characterized as an area with a reduced cerebral blood flow, increased oxygen extraction fraction and preserved cerebral metabolic rate of oxygen using positron emission tomography (PET) with radiolabeled O 2 . Because this imaging method is not feasible in an acute clinical setting, the magnetic resonance imaging (MRI) mismatch between perfusion-weighted imaging and diffusion-weighted imaging, as well as computed tomography perfusion have been proposed as surrogate markers to identify the penumbra in acute ischemic stroke patients. Transversal studies comparing PET and MRI or using longitudinal assessment of a limited sample of patients have been used to define perfusion thresholds. However, in the era of mechanical thrombectomy, these thresholds are debatable. Using various MRI methods, the original penumbra definition has recently gained a significant interest. The aim of this review is to provide an overview of the evolution of the ischemic penumbra imaging methods, including their respective strengths and limitations, as well as to map the current intellectual structure of the field using bibliometric analysis and explore future directions., Competing Interests: LC, DR, and TB are employees of Olea Medical, a company developing the OleaSphere platform including pipelines for ischemic penumbra. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chalet, Boutelier, Christen, Raguenes, Debatisse, Eker, Becker, Nighoghossian, Cho, Canet-Soulas and Mechtouff.)

Background: Metacarpal nonunion is a rare condition. The osteogenic capacity of periosteal free flap was investigated in five patients with metacarpal nonunion and impaired bone vascularization., Patients and Methods: Surgery was performed between 64 and 499 days after the initial bone osteosynthesis. The average age was 27.6 (range 16-32) years. Nonunion was caused by excessive periosteal removal in two patients, extensive open trauma in three. Four nonunions were diaphyseal, one metaphyseal. A periosteal medial femoral condyle free flap was raised on the descending genicular artery for four patients, the superomedial genicular artery for one. After osteosynthesis with a plate, the flap was wrapped around the metacarpal, overlapping the bone proximally and distally. The recipient vessel were the dorsal branch of the radial artery and a vena comitans in the anatomical snuffbox in four patients, at the base of the first webspace in one., Results: The flap size ranged from 5 × 3.5 cm to 8 × 4 cm. No postoperative complication occurred. Radiological bone union was achieved 3 to 8 months after surgery. One patient had a full range of motion, one a slight extension lag of the proximal interphalangeal joint, two moderate joint stiffness of the proximal interphalangeal or metacarpophalangeal joint (one requiring plate removal and extensor tenolysis), one severe stiffness that allowed using a hook grip which was the aim of the surgery., Conclusion: In case of metacarpal nonunion with impaired bone vascularization, the periosteal medial femoral condyle free flap provides an effective and biomimetic approach to bone healing., (© 2021 The Authors. Microsurgery published by Wiley Periodicals LLC.)

We investigated the role of three-dimensional (3-D) CT in the diagnosis and management of four bipartite scaphoids in three patients. We computed the volume ratio, moment of inertia ratio and direction vector from the centroid of the scaphoid to the os centrale carpi. We found that the os centrale carpi was always smaller than the scaphoid and showed an elongated shape in the scaphoid longitudinal axis. Its position was always posterior compared with the scaphoid anteroposterior axis. The main morphological feature of bipartite scaphoids was the continuity of the scaphoid from its proximal to distal aspect along the longitudinal axis. These criteria from 3-D imaging should be considered useful in the diagnosis of bipartite scaphoid as it allows differentiation from nonunion. 3-D single-photon emission computed tomography (SPECT)/CT was helpful in the surgical decision-making when the patient was symptomatic. 3-D imaging was also used for the preoperative simulation and planning of bone fusion as it simplifies surgery and makes it more accurate. Here we provide clear criteria for diagnosing bipartite scaphoids and for the planning when surgery is deemed necessary.

High adiponectin concentrations are generally regarded as beneficial with regard to cardiometabolic health, but have been paradoxically associated with increased cardiovascular disease risk, specifically heart failure, in individuals at high cardiovascular risk. We aimed to investigate the association between adiponectin and heart function parameters, and inversely, we estimated the effect of genetically-determined heart function and NT-proBNP as the main marker of heart failure on adiponectin using Mendelian randomisation. Observational analyses between adiponectin and measures of heart function, i.e. E/A ratio, left, and right ventricular ejection fraction, were performed in participants of the Netherlands Epidemiology of Obesity (NEO) study, assessed by MRI of the heart (n = 1,138). Two-sample Mendelian randomisation analyses were conducted to estimate the effect of NT-proBNP and heart function on adiponectin concentrations using publicly-available summary statistics (ADIPOGen; the PLATO trial). The mean (standard deviation) age was 56 (6) years and mean body mass index was 26 (4) kg/m 2 . Per five μg/mL higher adiponectin, the E/A ratio was -0.05 (95 % CI: -0.10, -0.01) lower, left ventricle ejection fraction was -0.5 % (95 % CI: -1.1, 0.1) lower, and right ventricle ejection fraction was 0.5 % (95 % CI: -0.1, 1.2) higher. Genetically-determined NT-proBNP was causally related to adiponectin concentrations in ADIPOGen: per doubling of genetically-determined NT-proBNP, adiponectin concentrations were 11.4 % (95 % CI: 1.7, 21.6) higher. With causal MR methods we showed that NT-proBNP affects adiponectin concentrations, while adiponectin is not associated with heart function parameters. Therefore, reverse causation may explain the adiponectin paradox observed in previous studies., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) has become standard treatment for elderly patients with symptomatic severe aortic valve stenosis. The ACURATE neo AS study evaluates 30-day and 1-year clinical and hemodynamic outcomes in patients treated with the ACURATE neo2 valve., Methods: The primary endpoint of this single-arm multicenter study is 30-day all-cause mortality. Other key endpoints include device performance, echocardiographic measures assessed by an independent core laboratory, and VARC-2 clinical efficacy and safety endpoints through 12 months., Results: The study enrolled 120 patients (mean age 82.1 ± 4.0 years; 67.5% female, mean baseline STS score 4.8 ± 3.8%). The VARC-2 composite safety endpoint at 30 days occurred in 13.3% of patients. All-cause mortality was 3.3% at 30 days and 11.9% at 1 year. The 30-day stroke rate was 2.5% (disabling stroke 1.7%); there were no new strokes between 30 days and 12 months. The rate of permanent pacemaker implantation was 15.0% (18/120) at 30 days and 17.8% (21/120) at 1 year. No patients required re-intervention for valve-related dysfunction and there were no cases of valve thrombosis or endocarditis. Patients demonstrated significant improvement in mean aortic valve gradient (baseline 38.9 ± 13.1 mmHg, 1 year 7.8 ± 3.5 mmHg; P < 0.001 in a paired analysis). In the overall population, paravalvular leak was evaluated at 1 year as none/trace in 60.5%, mild in 37.0%, and moderate in 2.5%; no patients had severe PVL., Conclusions: One-year outcomes from the ACURATE neo AS study support the safety and performance of TAVI with the ACURATE neo2 valve., (© 2021. The Author(s).)

Purpose: The spiral oblique retinacular ligament (SORL) procedure acts as a dynamic tenodesis to restore distal interphalangeal joint (DIP) extension and restrain proximal interphalangeal hyperextension. Despite the ingenious technique based on the oblique retinacular ligament anatomy, obtaining strong internal fixation remains an issue during the SORL procedure. We present a modified technique using the flexor digitorum profundus (FDP) hemi-tendon transfer., Methods: We dissected 5 fresh cadaveric specimens to evaluate morphometric parameters of the SORL procedure using the hemi-FDP. The volar groove of the FDP tendon was identified in zone I of the flexor sheath and the tendon was divided into radial and ulnar bundles. The selected hemi-tendon was divided at the proximal edge of the A1 pulley and a SORL procedure was performed through a transosseous tunnel in the distal phalanx. This technique was used in 3 patients with swan neck deformity., Results: The optimal distance between the DIP joint and the anterior drill hole of the transosseous tunnel was 7.6 mm (range, 6.8-8.5 mm). The relative loss of length of the tendon owing to the SORL path was 25.8 mm (range, 19.6-29.9 mm). In the clinical cases, the procedure improved DIP joint extension lag and prevented proximal interphalangeal joint hyperextension. Preserving one-half of the FDP allowed complete flexion of the DIP joint., Conclusions: The procedure is technically feasible. Its main advantages are that a distal suture is not required and that the substantial length of the tendon allows sturdy proximal internal fixation., Type of Study/level of Evidence: Therapeutic V., (Copyright © 2021 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Biomimicry consists in imitating nature to solve complex human problems. The hand surgeon usually tries to copy and recreate the structure-to-function and function-to-control relationships of the native tissues after damage. With its exceptional structure and biomechanics, the flexor digitorum superficialis (FDS) has been an important source of inspiration for artificial hand system reconstruction. The present systematic literature review highlights the twenty-two artificial hand system reconstructions derived from the FDS, and presents biomimicry as an alternative approach in clinical research in hand surgery., (Copyright © 2021 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Background: Ulnar nerve compression at the elbow level is the second-most common entrapment neuropathy. The aim of this study was to use shear-wave elastography for the quantification of ulnar nerve elasticity in patients after ulnar nerve decompression with anterior transposition and in the contralateral non-operative side., Method: Eleven patients with confirmed diagnosis and ulnar nerve decompression with anterior transposition were included and examinations were performed on an Aixplorer TM ultrasound system (Supersonic Imagine, Aix-en-Provence, France)., Results: We observed significant differences at 0-degree ( p < 0.001), 45-degree ( p < 0.05), 90-degree ( p < 0.01) and 120-degree ( p < 0.001) elbow flexion in the shear elastic modulus of the ulnar nerve in the operative and non-operative sides. There were no statistically significant differences between the elasticity values of the ulnar nerve after transposition at 0-degree elbow flexion and in the non-operative side at 120-degree elbow flexion ( p = 0.39), or in the ulnar nerve after transposition at 120-degree elbow flexion and in the non-operative side at 0-degree elbow flexion ( p = 0.09)., Conclusion: Shear-wave elastography has the potential to be used postoperatively as a method for assessing nerve tension noninvasively by the estimation of mechanical properties, such as the shear elastic modulus.

Magnetic resonance fingerprinting (MRF) is a quantitative MRI (qMRI) framework that provides simultaneous estimates of multiple relaxation parameters as well as metrics of field inhomogeneity in a single acquisition. However, current challenges exist in the forms of (1) scan time; (2) need for custom image reconstruction; (3) large dictionary sizes; (4) long dictionary-matching time. This study aims to introduce a novel streamlined magnetic-resonance fingerprinting (sMRF) framework based on a single-shot echo-planar imaging (EPI) sequence to simultaneously estimate tissue T1, T2, and T2* with integrated B1 + correction. Encouraged by recent work on EPI-based MRF, we developed a method that combines spin-echo EPI with gradient-echo EPI to achieve T2 in addition to T1 and T2* quantification. To this design, we add simultaneous multi-slice (SMS) acceleration to enable full-brain coverage in a few minutes. Moreover, in the parameter-estimation step, we use deep learning to train a deep neural network (DNN) to accelerate the estimation process by orders of magnitude. Notably, due to the high image quality of the EPI scans, the training process can rely simply on Bloch-simulated data. The DNN also removes the need for storing large dictionaries. Phantom scans along with in-vivo multi-slice scans from seven healthy volunteers were acquired with resolutions of 1.1×1.1×3 mm 3 and 1.7×1.7×3 mm 3 , and the results were validated against ground truth measurements. Excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches. In the phantom scan, a strong linear relationship (R = 1-1.04, R 2 >0.96) was found for all parameter estimates, with a particularly high agreement for T2 estimation (R 2 >0.99). Similar findings are reported for the in-vivo human data for all of our parameter estimates. Incorporation of DNN results in a reduction of parameter estimation time on the order of 1000 x and a reduction in storage requirements on the order of 2500 x while achieving highly similar results as conventional dictionary matching (%differences of 7.4 ± 0.4%, 3.6 ± 0.3% and 6.0 ± 0.4% error in T1, T2, and T2* estimation). Thus, sMRF has the potential to be the method of choice for future MRF studies by providing ease of implementation, fast whole-brain coverage, and ultra-fast T1/T2/T2* estimation., Competing Interests: Declarations of Competing Interest Mahdi Khajehim holds a US patent application regarding the sMRF approach described in this manuscript (Publication Number: WO/2020/206553)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Recently, local anaesthesia has become popular among hand surgeons. We hypothesized that using the "wide awake local anaesthesia no tourniquet" (WALANT) approach would result in lower global costs and in an increase in the operating room (OR)'s efficiency., Methods: All cases of carpal tunnel (CTR) and trigger finger releases (TFR) performed over 2016 and 2017 were divided into four groups, following which the anaesthesia method was used. Total OR occupation time, surgical time and the "all but surgery" time were analysed. A common minimum bill per anaesthesia was generated., Results: WALANT or local anaesthesia and tourniquet increase the OR's throughput by having shorter operation room occupation times than other methods (17.5-33%). Costs of the two procedures are reduced by 21-31% when using local anaesthesia methods., Conclusion: Preferring those techniques for CTR and TFR has a notable beneficial impact on the costs and on the OR's efficiency. This effect is more evident on short surgical procedures. LOE: Level of evidence III, economic analysis., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The choice of the donor tendon in tendon reconstruction of the hand theoretically influences the results of the surgery because of the interactions of its structure with the healing process. The objective of our study was to specify the surgical bases of vascularized extensor indicis proprius (EIP) in tendon reconstruction of the hand and to present its application from a series of observations. According to our observations, the EIP's vascularization arises from a branch of the 2nd dorsal metacarpal artery, 3-4 cm proximally to the metacarpophalangeal joint (MCP). We demonstrate the feasibility and effectiveness of a vascularized EIP graft for finger flexor tendon reconstruction, for defects of the extensor mechanism at the MCP joint level and for reconstruction of the extensor pollicis longus. Our biomimetic approach in tendon reconstruction has led us to factor in the complexity of the tendon and peritendinous structure. The use of vascularized EIP offers theoretical advantages for the tendon healing process, demonstrates encouraging first results with interesting versatility and very low iatrogenicity., (Copyright © 2021 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The flexor carpi radialis brevis (FCRB) is a supernumerary musculotendinous structure of the wrist that has been the focus of some interest in the last decade. While its anatomy is well known, its in vivo function remains unknown as it has never been studied., Methods: Eleven cases of FCRB underwent a multimodal ultrasound consisting of B-mode, color Doppler and shear wave elastography., Results: A pennate shape was observed in all cases and the mean value of the cross-sectional area was 0.8 cm 2 (SD 0.3 cm 2 ). Young's modulus was significantly (p < 0.01) different between the resting position and active flexion or passive extension., Conclusion: Our study demonstrates that the FCRB shows biomechanics of a typical skeletal muscle and is voluntarily controlled by flexing the wrist. Absent in other vertebrate taxa, the FCRB probably plays a role in active stability of the wrist in Human.

This article presents an open source software able to convert, display, and process medical images. It differentiates itself from the existing software by its ability to design complex processing pipelines and to wisely execute them on a large databases. An MP3 pipeline can contain unlimited homemade or ready-made processes and can be carried out with a parallel execution system. As a viewer, MP3 allows display of up to four images together and to draw Regions Of Interest (ROI). Two applications showing the strengths of the software are presented as examples: a preclinical study involving Magnetic Resonance Imaging (MRI) data and a clinical one involving Computed Tomography (CT) images. MP3 is downloadable at https://github.com/nifm-gin/MP3., (Copyright © 2020 Brossard, Montigon, Boux, Delphin, Christen, Barbier and Lemasson.)

Background: High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD). Consumption of dark chocolate, which is high in flavonoids that may reduce CVD risk, is an attractive intervention to reduce to BP. Additionally, the use of mobile health (mHealth) technologies (eg, telehealth, smartphones, and wearable devices) can improve outcomes in patients with CVD., Objective: The purpose of this study was to investigate the impact of dark chocolate intake on BP, subject use of mHealth, and integration of mHealth into a clinical trial., Methods: The COCOA-BP (ChOcolate COnsumption And Blood Pressure) study was a prospective, single-center, pre-/postintervention study that enrolled 62 healthy volunteers. The study consisted of 3 phases: smartwatch/smart BP monitor familiarization and washout from chocolate (week 1); control (week 2); and intervention (weeks 3 and 4). During the intervention phase, subjects consumed 50 g of dark chocolate per day. The primary endpoint was change in resting systolic BP between the intervention and control phases. Additional endpoints included device accuracy and correlation with physical activity., Results: Mean resting systolic BP was 116.4 mm Hg before chocolate intake among 62 participants (mean age 37 years; 61% female). After chocolate intake, mean resting systolic BP was 116.0 mm Hg (difference -0.4; P = .69). These findings suggest that 2 weeks of dark chocolate intake did not reduce resting systolic BP. There was poor agreement between mHealth device and standard (nurse-performed) measurements., Conclusion: In this study, short-term dark chocolate intake did not seem to reduce BP. mHealth technology shows great potential for use in clinical studies, but challenges related to device accuracy and compliance need to be addressed., (© 2020 The Author(s).)

Background: The increase in serum triglyceride (TG) concentrations in response to a meal is considered a risk factor for cardiovascular disease. We aimed to elucidate the genetics of the postprandial TG response through genome-wide association studies (GWAS)., Methods: Participants of the NEO (Netherlands Epidemiology of Obesity) study (n=5630) consumed a liquid mixed meal after an overnight fast. GWAS of fasting and postprandial serum TG at 150 minutes were performed. To identify genetic variation of postprandial TG independent of fasting TG, we calculated the TG response at 150 minutes by the residuals of a nonlinear regression that predicted TG at 150 minutes as a function of fasting TG. Association analyses were adjusted for age, sex, and principal components in a linear regression model. Next, using the identified variants as determinants, we performed linear regression analyses on the residuals of the postprandial response of 149 nuclear magnetic resonance-based metabolite measures., Results: GWAS of fasting TG and postprandial serum TG at 150 minutes resulted in completely overlapping loci, replicating previous GWAS. From GWAS of the TG response, we identified rs7350789-A (allele frequency=0.36), mapping to hepatic lipase ( LIPC ), to be associated with a smaller increase in TG concentrations at 150 minutes (β=-0.11; P -value=5.1×10 -8 ). Rs7350789-A was associated with responses of 33 metabolite measures ( P -value <1.34×10 -3 ), mainly smaller increases of the TG-component in almost all HDL (high-density lipoprotein) subparticles (HDL-TG), a smaller decrease of HDL diameter and smaller increases of most components of VLDL (very low density lipoprotein) subparticles., Conclusions: GWAS of the TG response identified a variant near LIPC as a main contributor to postprandial TG metabolism independent of fasting TG concentrations, resulting in smaller increases of HDL-TG and VLDL subparticles.

Background and Aims: In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance., Methods and Results: In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm 2 and aSAT of 300 (111) cm 2 . Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59-70), 33% (95%CI: 28-42) and 20% (95%CI: 14-26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women., Conclusion: Where leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to what extent this association is influenced by total body fat. Therefore, we aimed to examine the association between serum leptin and blood coagulation while taking total body fat into account in a population-based cohort study., Methods: We performed a cross-sectional analysis with baseline measurements of 5797 participants of the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort of middle-aged men and women. We examined associations between serum leptin concentration and coagulation factor concentrations and parameters of platelet activation in linear regression analyses. All analyses were adjusted for multiple covariates, including total body fat., Results: In multivariable adjusted analyses a 1 μg/L higher serum leptin concentration was associated with a 0.22 IU/dL (95% CI: 0.11, 0.32) higher FVIII concentration and a 0.20 IU/dL (95% CI: 0.14, 0.27) higher FIX concentration (3.5 IU/dL FVIII and 3.2 IU/dL FIX per SD leptin). Serum leptin concentration was not associated with FXI, fibrinogen, platelet count, mean platelet volume and platelet distribution width in multivariable adjusted analyses., Discussion: This study showed that serum leptin concentration was associated with higher concentrations of FVIII and FIX in an observational study, which could be clinically relevant., Competing Interests: Declaration of competing interest The authors state that they have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9., Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration., Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable., Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

Background and Aims: Inflammation may underlie the association between obesity, atherosclerosis and cardiovascular disease. We investigated to what extent markers of inflammation mediate associations between overall and visceral body fat and subclinical atherosclerosis., Methods and Results: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study we estimated total body fat (TBF) by bio-impedance analysis, carotid artery intima media thickness (cIMT) by ultrasound, C-reactive protein (hs-CRP) and glycoprotein acetyls (GlycA) concentrations in fasting blood samples (n = 5627), and visceral adipose tissue (VAT) by magnetic resonance imaging (n = 2247). We examined associations between TBF and VAT, and cIMT using linear regression, adjusted for potential confounding factors, and for mediators: cardiometabolic risk factors (blood pressure, glucose and low-density lipoprotein cholesterol), and inflammation using CRP and GlycA as proxies. Mean (SD) cIMT was 615 (90) μm. Per SD of TBF (8%), cIMT was 19 μm larger (95% confidence interval, CI: 10, 28). This association was 17 μm (95% CI: 8, 27) after adjustment for cardiometabolic risk factors, and did not change after adjustment for markers of inflammation. Per SD (56 cm 2 ) VAT, cIMT was 9 μm larger (95% CI: 2, 16) which changed to 5 μm (95% CI: -3, 12) after adjustment for cardiometabolic risk factors, and did not change after adjustment for inflammatory markers., Conclusion: Our results suggest that associations between measures of overall and visceral body fat and subclinical atherosclerosis are not mediated by inflammation as measured by CRP and GlycA. Obesity may exert cardiovascular risk via other markers of systemic inflammation., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: The goal of this analysis was to evaluate the final 5-year safety and effectiveness of the PROMUS Element platinum-chromium everolimus-eluting stent in unselected patients treated in routine clinical practice., Background: The prospective, open-label PROMUS Element™ European Post-Approval Surveillance Study (PE-PROVE) enrolled 1,010 "real-world" patients who received the PROMUS Element stent. Adverse event rates were low at 1-year, and the incidence of stent thrombosis was 0.6%., Methods: The primary endpoint was target vessel failure (TVF; overall and PE stent-related), a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel revascularization (TVR) at 1-year post-implantation. Five-year clinical outcomes were evaluated in overall as well as high-risk patient subgroups., Results: The overall 5-year TVF rate was 14.9%, with 7.0% being related to the study stent. Cardiac death, MI and TVR related to the study stent occurred in 0.5%, 3.2%, and 5.7%, respectively. Stent thrombosis through 5-year follow-up was 1.0%. The rates of overall and study stent related TVF were numerically higher in patients with medically treated diabetes, long lesions (≥28 mm), and small diameter vessels (≤2.5 mm) compared to the overall study population. Additionally, favorable stent thrombosis rates through 5 years were reported for the PROMUS Element stent in these high-risk subgroups., Conclusions: The final 5-year data from the PE-PROVE study demonstrate favorable outcomes and low rates of adverse events with the PE stent when used in "real-world" patients with coronary artery disease., (© 2018 Wiley Periodicals, Inc.)

Background: Recent advancements in simultaneous multi-slice (SMS) imaging techniques have enabled whole-brain resting-state fMRI (rs-fMRI) scanning at sub-second temporal resolution, providing spectral ranges much wider than the typically used range of 0.01-0.1 Hz. However, the advantages of this accelerated acquisition for rs-fMRI have not been evaluated., New Method: In this study, we used SMS Echo Planar Imaging (EPI) to probe whole-brain functional connectivity with a short repetition time (TR = 350 ms) and compared it with standard EPI with a longer TR of 2000 ms. We determined the effect of scan length and investigated the temporal filtration strategies that optimize results based on metrics of signal-noise separation and test-retest reliability using both seed-based and independent component analysis (ICA)., Results: We found that use of either the entire frequency range of 0.01-1.4 Hz or the entire frequency range with the exclusion of typical cardiac and respiratory frequency values tended to provide the best functional connectivity maps., Comparison With Existing Methods: We found that the SMS-acquired rs-fMRI scans had improved the signal-noise separation, while preserving the same level of test-retest reliability compared to conventional EPI, and enabled the detection of reliable functional connectivity networks with scan times as short as 3 min., Conclusions: Our findings suggest that whole-brain rs-fMRI studies may benefit from the increased temporal resolution enabled by the SMS-EPI acquisition, leading to drastic scan time reductions, which in turn should enable the more widespread use of rs-fMRI in clinical research protocols., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: While extended dual antiplatelet therapy (DAPT) with aspirin and a platelet (P2Y 12 ) inhibitor after percutaneous coronary intervention (PCI) reduces the risk of stent thrombosis (ST) and myocardial infarction (MI), it also increases bleeding. Newer generation drug-eluting stents with bioabsorbable polymer coatings may reduce thrombotic events and allow abbreviated DAPT in selected patients. The EVOLVE Short DAPT study is designed to evaluate the safety of 3-month DAPT in high bleeding risk subjects treated with the SYNERGY bioabsorbable polymer everolimus-eluting stent., Trial Design: EVOLVE Short DAPT is a prospective, single-arm, international study that enrolled 2009 high risk bleeding subjects (defined as age ≥75 years, chronic anticoagulation, major bleeding within 12 months, history of stroke, renal insufficiency/failure, or thrombocytopenia) who underwent PCI with the SYNERGY stent. Subjects presenting with acute MI or complex lesions were excluded. After 3 months treatment with DAPT (except those on anticoagulant in whom aspirin is optional), subjects free from stroke, MI, revascularization or ST will be eligible to discontinue P2Y 12 inhibitor, but continue aspirin. Co-primary endpoints assessed between 3-15 months are: i) death/MI compared for non-inferiority with propensity-adjusted historical group receiving 12-month DAPT, and ii) definite/probable ST compared to a performance goal. The secondary endpoint is the rate of bleeding in subjects not receiving chronic anticoagulation compared for superiority against a propensity-adjusted historical control., Conclusion: The EVOLVE Short DAPT study will prospectively define the safety of DAPT discontinuation at 3 months in high bleeding risk patients treated with the SYNERGY stent., (Copyright © 2018 Elsevier Inc. All rights reserved.)

It is debated whether sex differences in adiponectin and leptin are due to sex differences in body fat distribution. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, associations of measures of body fat and sex with serum adiponectin and leptin concentrations were examined using linear regression analysis (n = 6494, VAT: n = 2516). Sex differences were additionally adjusted for the measure of body fat that was most strongly associated with adiponectin or leptin concentrations. Median adiponectin concentrations in women and men were 10.5 mg/L (IQR, interquartile range: 7.7-13.9) and 6.1 mg/L (IQR: 4.5-8.2), mean difference 4.6 mg/L (95% CI: 4.3, 4.9). Median leptin concentrations in women and men were 19.2 μg/L (IQR: 11.5-30.0) and 7.1 μg/L (IQR: 4.6-11.1), mean difference 15.1 μg/L (95% CI: 14.4, 15.8). VAT was most strongly associated with adiponectin, total body fat percentage was most strongly associated with leptin. After adjustment for VAT, women had 3.8 mg/L (95% CI: 3.3, 4.3) higher adiponectin than men. After adjustment for total body fat percentage, leptin concentrations in women were 0.4 μg/L lower than in men (95% CI: -1.2, 2.0). One genetic variant (rs4731420) was associated with extreme leptin concentrations (>100 μg/L) in women: odds ratio 2.8 (95% CI: 1.7, 4.6). Total body fat percentage was strongly associated with leptin concentrations. Higher leptin concentrations in women than in men were completely explained by differences in total body fat percentage. Visceral fat was associated with adiponectin concentrations, and did not completely explain higher adiponectin concentrations in women than in men., (Copyright © 2018. Published by Elsevier Inc.)

In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the temporal correlation between spontaneous blood oxygen level-dependent signal fluctuations of spatially remote brain regions. Recently, several groups have shown that temporal shifts are present in rs-fMRI maps in patients with cerebrovascular disease due to spatial differences in arterial arrival times, and that this can be exploited to map arrival times in the brain. This suggests that rs-fMRI connectivity mapping may be similarly sensitive to such temporal shifts, and that standard rs-fMRI analysis methods may fail to identify functional connectivity networks. To investigate this, we studied the default mode network (DMN) in Moyamoya disease patients and compared it with normal healthy volunteers. Our results show that using standard independent component analysis (ICA) and seed-based approaches, arterial arrival delays lead to inaccurate incomplete characterization of functional connectivity within the DMN in Moyamoya disease patients. Furthermore, we propose two techniques to correct these errors, for seed-based and ICA methods, respectively. Using these methods, we demonstrate that it is possible to mitigate the deleterious effects of arterial arrival time on the assessment of functional connectivity of the DMN. As these corrections have not been applied to the vast majority of >200 prior rs-fMRI studies in patients with cerebrovascular disease, we suggest that they be interpreted with great caution. Correction methods should be applied in any rs-fMRI connectivity study of subjects expected to have abnormally delayed arterial arrival times.

Background: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk., Methods: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium)., Results: In the discovery analysis (n=4248), we identified 3 independent variants ( P <5×10 -8 ) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to CETP and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (-0.23 mmol/L; 95% confidence interval, -0.26 to -0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00-0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94-1.23) for CAD risk., Conclusions: This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol., (© 2018 American Heart Association, Inc.)

Aims: Long-term data on bioabsorbable polymer-coated everolimus-eluting stents (BP-EES) are limited. The EVOLVE trial compared the safety and efficacy of two dose formulations of the SYNERGY BP-EES with the permanent polymer-coated PROMUS Element EES (PE)., Methods and Results: The EVOLVE study was a prospective, multicentre, non-inferiority trial that randomised 291 patients with de novo coronary lesions (length: ≤28 mm; diameter: ≥2.25 to ≤3.5 mm) to receive PE (n=98), SYNERGY (n=94), or SYNERGY half-dose (n=99). At five years, there were no significant differences in the rates of TLF or individual components between groups. TLR rates trended lower in both SYNERGY arms than in the PE arm (TLR: 1.1% SYNERGY and 1.0% SYNERGY half-dose vs. 6.1% PE; p=0.07 and p=0.06, respectively). TVR was numerically lower in the SYNERGY arms compared to the PE arm (TVR: 3.3% SYNERGY and 4.2% SYNERGY half-dose vs. 10.2% PE; p=0.06 and p=0.11, respectively). No incidence of stent thrombosis was reported in any arm up to five years., Conclusions: The EVOLVE trial represents the longest-term follow-up of the SYNERGY stent available to date, demonstrating its continued safety and efficacy for the treatment of selected de novo atherosclerotic lesions up to five years.

Wide awake local anesthesia no tourniquet (WALANT) hand surgery is a rapidly growing in popularity. WALANT has been used by hand surgeons when operating on bones, tendons, ligaments, nerve entrapments. We offer a case report of the first case in the literature describing WALANT technique when performing trapeziometacarpal joint arthroplasty with prosthesis implantation. We offer technical points on how to perform this procedure and the advantages that are associated with using WALANT for prosthesis arthroplasty.

OBJECTIVE Chronic neuropathic pain after peripheral nerve injury is a major clinical problem. Its management is difficult, and therapeutic approaches vary and include oral medication, neurostimulation, and surgery. The aim of this study was to assess the adequacy of surgical nerve revision in a large series of patients with long-term follow-up. METHODS The authors reviewed the charts of 231 patients (335 nerve injuries) who experienced neuropathic pain after peripheral nerve injury and underwent surgery for nerve revision at the authors' institution between 1997 and 2012. The following parameters were recorded for each patient: history, location, duration, and severity of the pain and details of nerve revision surgery. In addition, patients were invited to participate in a follow-up consultation and were asked to score their pain at that time. Current medications and examination findings were also documented. RESULTS Elective surgery was the source of nerve injury for 55.4% of the patients. The lower extremity was the most commonly involved anatomical region (54.3%), followed by the lower abdomen (16.4%) and the thoracic region (13%). The mean time between the onset of injury and revision surgery was 48 months. On average, 1.3 injured nerves per patient were explored, and surgery was performed 1.2 times per patient. Each nerve underwent revision 1.1 times on average. Neuromas-in-continuity and scar-tethered nerves were observed in 205 nerves (61%) and terminal neuromas were observed in 130 nerves (39%). The authors performed 186 (56%) neurolyses and 149 (44%) neuroma resections and translocations. The mean follow-up of the 127 (55%) patients who agreed to come back for a consultation was 68 months. These patients indicated an average pain decrease of 4 points in the visual analog scale (VAS) score. Pain relief greater than a 2-point decrease on the VAS, a criterion for a successful treatment according to the European Federation of Neurological Societies guidelines, was encountered in 80% of patients. Pain relief did not vary in a statistically significant way with regard to surgical technique, age and sex of the patient, affected nerve, or time between trauma and surgery. Before surgery, 76% of the patients were on a regimen of paracetamol and/or NSAIDs and 44% received opiates, while after nerve revision only 37% still required simple analgesia and 14% needed opiates. CONCLUSIONS Bearing in mind that medication achieves satisfying pain relief in only 30%-40% of patients with neuropathic pain, surgery must be considered as an effective alternative therapy. No objective criteria were shown to be factors of poor prognosis. Systematic preoperative clinical mapping of the injured nerves and diagnostic nerve blocks could improve the primary success rate of the surgery.

Background: Several trials to prevent cardiovascular disease by inhibiting cholesteryl ester transfer protein (CETP) have failed, except Randomized EValuation of the Effects of Anacetrapib through Lipid-modification. Thus far, it is unclear to what extent CETP is causally related to measures of atherosclerosis., Objective: The aim of the article was to study the causal relationship between genetically determined CETP concentration and carotid intima-media thickness (cIMT) in a population-based cohort study., Methods: In the Netherlands Epidemiology of Obesity study, participants were genotyped, and cIMT was measured by ultrasonography. We examined the relation between a weighted genetic risk score for CETP concentration, based on 3 single-nucleotide polymorphisms that have previously been shown to largely determine CETP concentration and cIMT using Mendelian randomization in the total population and in strata by sex, Framingham 10-year risk, (pre)diabetes, high-density lipoprotein cholesterol, triglycerides, and statin use., Results: We analyzed 5655 participants (56% women) with a mean age of 56 (range 44-66) years, body mass index of 26 (range 17-61) kg/m 2 , and serum CETP of 2.47 (range 0.68-5.33) μg/mL. There was no evidence for a causal relation between genetically determined CETP and cIMT in the total population, but associations were differently directed in men (16 μm per μg/mL increase in genetically determined CETP; 95% confidence interval: -8, 39) and women (-8 μm; -25, 9). Genetically determined CETP appeared to be associated with cIMT in normoglycemic men (26 μm; -1, 52) and in (pre)diabetic women (48 μm; -2, 98)., Conclusion: In this population-based study, there was no causal relation between genetically determined CETP concentration and cIMT in the total population although we observed directionally differing effects in men and women. Stratified results suggested associations in individuals with different cardiometabolic risk factor profiles, which require replication., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Human papillomavirus (HPV), and the related, cervical intraepithelial neoplasia (CIN), are common yet poorly understood physical conditions. The diagnosis of HPV often elicits shame and guilt, which in turn may undermine psychological and physical health. The current study compared shame and guilt responses to diagnosis among two groups: women diagnosed with HPV/CIN and women diagnosed with Epstein-Barr Virus (EBV/IM). Eighty women recently diagnosed with HPV/CIN or EBV/IM completed measures of shame- and guilt-proneness, shame and guilt following diagnosis, and disease knowledge including prevalence estimates (HPV and EBV, respectively). HPV/CIN (vs. EBV/IM) predicted more diagnosis-related shame and guilt. Estimates of high prevalence interacted with diagnosis and shame-proneness to predict diagnosis-related shame. Simple slope analyses indicated that in women with HPV/CIN reporting low-to-average shame-proneness, high prevalence estimates reduced diagnosis-related shame; however, women high in shame-proneness experienced high diagnosis-related shame regardless of more accurate prevalence estimates. Women high in shame-proneness appear to be particularly vulnerable to HPV-related shame even when they are aware that it is very common.

Purpose: To simultaneously assess reproducibility of three MRI transverse relaxation parameters ( R2', R2*, and R 2 ) for brain tissue oxygenation mapping and to assess changes in these parameters with inhalation of gases that increase and decrease oxygenation, to identify the most sensitive parameter for imaging brain oxygenation., Materials and Methods: Forty-eight healthy subjects (25 male, ages 35 ± 8 years) were scanned at 3.0 Tesla, each with one of four gases (mildly and strongly hypercapnic and hypoxic) administered in a challenge paradigm, using a gas delivery setup designed for patient use. Cerebral blood flow mapping with arterial spin labeling, and simultaneous R2', R2*, and R 2 mapping with gradient-echo sampling of free induction decay and echo (GESFIDE) were performed. Reproducibility in air and gas-induced changes were evaluated using nonparametric analysis with correction for multiple comparisons., Results: Our gas delivery setup achieved stable gas challenges as shown by physiological monitoring. Test-retest variability of R2', R2*, and R 2 were found to be 0.24 s -1 (8.6% of mean), 0.24 s -1 (1.3% of mean), and 0.15 s -1 (1.0% of mean), respectively. Strong hypoxia produced the most conclusive oxygenation-driven relaxation change, inducing increases in R2' (25 ± 13%, P = 0.03), R2* (5 ± 2%, P = 0.02), and R 2 (2 ± 2%, NS)., Conclusion: We benchmarked the intra-scan test-retest variability in GESFIDE-based transverse relaxation rate mapping. Using a reliable framework for gas challenge paradigms, we recommend strong hypoxia for validating oxygenation mapping methods, and the use of tissue R2' change, instead of R2* or R 2 , as a metric for studying brain tissue oxygenation using transverse relaxation methods., Level of Evidence: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:704-714., (© 2017 International Society for Magnetic Resonance in Medicine.)