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Background and Objectives: Acute ischemic stroke patients with a large vessel occlusion (LVO) who present to a primary stroke center (PSC) often require transfer to a comprehensive stroke center (CSC) for thrombectomy. Not much is known about specific characteristics at the PSC that are associated with infarct growth during transfer. Gaining more insight into these features could aid future trials with cytoprotective agents targeted at slowing infarct growth. We aimed to identify baseline clinical and imaging characteristics that are associated with fast infarct growth rate (IGR) during interhospital transfer., Methods: We included patients from the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project, a prospective multicenter study. Patients with an anterior circulation LVO who were transferred from a PSC to a CSC for consideration of thrombectomy were eligible if imaging criteria were fulfilled. A CT perfusion (CTP) needed to be obtained at the PSC followed by an MRI at the CSC, before consideration of thrombectomy. The interhospital IGR was defined as the difference between the infarct volumes on MRI and CTP, divided by the time between the scans. Multivariable logistic regression was used to determine characteristics associated with fast IGR (≥5 mL/h)., Results: A total of 183 patients with a median age of 74 years (interquartile range 61-82), of whom 99 (54%) were male and 82 (45%) were fast progressors, were included. At baseline, fast progressors had a higher NIH Stroke Scale score (median 16 vs 13), lower cerebral blood volume index (median 0.80 vs 0.89), more commonly poor collaterals on CT angiography (35% vs 13%), higher hypoperfusion intensity ratios (HIRs) (median 0.51 vs 0.34), and larger core volumes (median 11.80 mL vs 0.00 mL). In multivariable analysis, higher HIR (adjusted odds ratio [aOR] for every 0.10 increase 1.32 [95% CI 1.10-1.59]) and larger core volume (aOR for every 10 mL increase 1.54 [95% CI 1.20-2.11]) remained independently associated with fast IGR., Discussion: Fast infarct growth during interhospital transfer of acute stroke patients is associated with imaging markers of poor collaterals on baseline imaging. These markers are promising targets for patient selection in cytoprotective trials aimed at reducing interhospital infarct growth.

Background: Deep venous outflow (VO) may be an important surrogate marker of collateral blood flow in acute ischemic stroke patients with a large vessel occlusion (AIS-LVO). Researchers have yet to determine the relationship between deep VO status in late-window patients and imaging measures of collaterals, which are key in preserving tissue., Materials and Methods: We performed a multicenter retrospective cohort study on a subset of DEFUSE 3 patients recruited across 38 centers between May 2016 and May 2017 who underwent successful thrombectomy revascularization. Internal cerebral vein opacification was scored on a scale of 0-2. This metric was added to the cortical vein opacification score to derive the comprehensive VO (CVO) score from 0 to 8. Patients were stratified by favorable (ICV+) and unfavorable (ICV-) ICV scores, and similarly CVO+ and CVO-. Analyses comparing outcomes were primarily conducted by Mann-Whitney U and χ 2 tests., Results: Forty-five patients from DEFUSE 3 were scored and dichotomized into CVO+, CVO-, ICV+, and ICV- categories, with comparable demographics. Hypoperfusion intensity ratio, a marker of tissue level collaterals, was significantly worse in the ICV- and CVO- groups (p = 0.005). ICV- alone was also associated with a larger perfusion lesion (138 ml vs 87 ml; p = 0.023). No significant differences were noted in functional and safety outcomes., Conclusions: Impaired deep venous drainage alone may be a marker of poor tissue level collaterals and a greater degree of affected tissue in AIS-LVO patients presenting in the late-window who subsequently undergo successful revascularization., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.C. discloses equity and consulting for iSchemaView. G.W.A. discloses equity and consulting for iSchemaView and consulting for Genentech. J.F. discloses grants and personal fees from Acandis, Cerenovus, MicroVention,Medtronic, and Stryker, grants from Route 92, and personal fees from Phenox and Penumbra outside of the submitted work. J.J.H. discloses consulting for Medtronic and MicroVention and membership of the medical and scientific advisory board for iSchemaView.

Background: Cardiogenic shock (CS) presents a medical challenge with limited treatment options. Positive end-expiratory pressure (PEEP) during mechanical ventilation has been linked with clinical benefits in patients with CS. We investigated if increasing PEEP levels could unload the left ventricle (LV) in CS in a large animal model of LV-CS., Methods: LV-CS was induced in 26 female pigs (60 kg) by microsphere injections into the left main coronary artery. In one study protocol PEEP was increased (5, 10, and 15 cmH2O) and then reverted (15, 10, 5 cmH2O) in 3-minute intervals. In another protocol PEEP increments with higher granularity were conducted through 3-minute intervals (5, 8, 10, 13, and 15 cmH2O). Hemodynamic measurements were performed at all PEEP levels during the healthy state and LV-CS with LV pressure-volume loops. The primary endpoint was pressure-volume area (PVA). Secondary endpoints included other mechano-energetic parameters and estimates of LV preload and afterload., Results: Cardiac output (CO) decreased significantly in LV-CS from 4.5±1.0 L/min to 3.1±0.9 L/min (P<0.001). Increasing PEEP resulted in lower PVA, demonstrating a 36±3% decrease in the healthy state (P<0.001) and 18±3% in LV-CS (P<0.001) at PEEP 15 cmH2O. These effects were highly reversible when PEEP was returned to 5 cmH2O. While mean arterial pressure declined with higher PEEP, CO remained preserved during LV-CS (P=0.339). Increasing PEEP caused reductions in key measures of LV preload and afterload during LV-CS. Right ventricular stroke work index was decreased with increased PEEP. Despite a minor increase in heart rate (HR) at PEEP levels of 15 cmH2O (71 bpm vs. 75 bpm, p<0.05), total mechanical power expenditure (PVA normalized to HR) decreased at higher PEEP., Conclusions: Applying higher PEEP levels reduced PVA, preserving CO while decreasing MAP. PEEP could be a viable LV unloading strategy if titrated optimally during LV-CS., Competing Interests: Conflicts of interest: Henrik Wiggers has been the principal or a sub-investigator in studies involving the following pharmaceutical companies: MSD, Bayer, Daiichi-Sankyo, Novartis, Novo Nordisk, Sanofi-Aventis, and Pfizer. The other authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists.)

Background: Excessive or improper use of dietary supplements (DSs) by athletes may cause adverse effects, such as impaired performance or failing a doping test, making it important for athletes to mitigate risk and make well-informed choices when using supplements. Methods: This study used focus group interviews to examine the attitudes, motivations, and practices related to DSs among male elite ice hockey players. Results: The players used a wide range of products, ranging from vitamins to multi-ingredient pre-workout supplements. Consuming DSs was considered as a practical and convenient way to ingest sufficient calories to gain or maintain the body weight and muscle mass needed to meet the physical requirements of the sport. The athletes demonstrated a lenient and ignorant attitude when acquiring and using supplements, with a non-critical trust in the guidance provided to them by the coach or physician. Having completed basic anti-doping education in the form of an e-learning program did not appear to result in taking a more careful approach to using DSs. Conclusions: Through their DS practices, elite ice hockey players may put themselves at risk for anti-doping rule violations. A comprehensive approach is needed when aiming to prevent unintentional doping in this athlete cohort.

Introduction: Direct-acting antivirals (DAAs) are key to eliminating hepatitis C virus (HCV). In men who have sex with men (MSM) with HIV co-infection, recently acquired HCV infection is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates., Methods: The cohort included MSM with recently acquired HCV infection from 2014 to 2021. The patients' demographic, clinical, behavioural, and laboratory data and treatment and reinfection outcomes were documented., Results: A total of 237 men with recently acquired HCV infection were included: 216 (91%) had HIV. The median age was 46 years (interquartile range [IQR] 39-52), and the median CD4 count was 660/mm 3 (IQR 527-835). The annual incidence of recently acquired HCV remained between 0.28% and 0.43% but dropped to 0.02% in 2021 during the COVID pandemic, almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95% confidence interval 12.6-18.8), and reinfection was associated with the use of crystal methamphetamine (p = 0.032) and ketamine (p = 0.042). In total, 31.3% had multiple reinfections, and four reinfections occurred in users of pre-exposure prophylaxis., Conclusions: High treatment and cure rates did not lead to HCV elimination. A change in sexual behaviour, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As recently acquired HCV is prevalent in MSM with and without HIV, surveillance is necessary to consolidate elimination goals., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Patients with acute ischemic stroke with a large vessel occlusion (LVO) admitted to non endovascular-capable centers often require inter-hospital transfer for thrombectomy. We aimed to describe the incidence of substantial clinical change during transfer, the factors associated with clinical change, and its relationship with 3-month outcome., Methods: We analyzed data from two cohorts of acute stroke patients transferred for thrombectomy to a comprehensive center (Stanford, USA, November 2019 to January 2023; Montpellier, France, January 2015 to January 2017), regardless of whether thrombectomy was eventually attempted. Patients were included if they had evidence of an LVO at the referring hospital and had a National Institute of Health Stroke Scale (NIHSS) score documented before and immediately after transfer. Inter-hospital clinical change was categorized as improvement (⩾4 points and ⩾25% decrease between the NIHSS score in the referring hospital and upon comprehensive center arrival), deterioration (⩾4 points and ⩾25% increase), or stability (neither improvement nor deterioration). The stable group was considered as the reference and was compared to the improvement or deterioration groups separately., Results: A total of 504 patients were included, of whom 22% experienced inter-hospital improvement, 14% deterioration, and 64% were stable. Pre-transfer variables independently associated with clinical improvement were intravenous thrombolysis use, more distal occlusions, and lower serum glucose; variables associated with deterioration included more proximal occlusions and higher serum glucose. On post-transfer imaging, clinical improvement was associated with arterial recanalization and smaller infarct growth and deterioration with larger infarct growth. As compared to stable patients, those with clinical improvement had better 3-month functional outcome (adjusted common odds ratio (cOR) = 2.43; 95% confidence interval (CI) = 1.59-3.71; p  < 0.001), while those with deterioration had worse outcome (adjusted cOR = 0.60; 95% CI = 0.37-0.98; p  = 0.044)., Conclusion: Substantial inter-hospital clinical changes are frequently observed in LVO-related ischemic strokes, with significant impact on functional outcome. There is a need to develop treatments that improves the clinical status during transfer., Data Access Statement: The data that support the findings of this study are available upon reasonable request., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr J.J.H. reports consulting fees from Medtronic and MicroVention, and he is a member of the medical and scientific advisory board for iSchemaView; Dr G.W.A. reports stock holdings in iSchemaView; compensation from Biogen, iSchemaView, and Genentech for consultant services. Other authors have nothing to disclose.

Objectives: To identify sexual/sex-associated risk factors for hepatitis C transmission among men who have sex with men (MSM) and visualise behavioural trajectories from 2019 to 2021., Methods: We linked a behavioural survey to a hepatitis C cohort study (NoCo), established in 2019 across six German HIV/hepatitis C virus (HCV) treatment centres, and performed a case-control analysis. Cases were MSM with recent HCV infection, and controls were matched for HIV status (model 1) or proportions of sexual partners with HIV (model 2). We conducted conditional univariable and multivariable regression analyses., Results: In all, 197 cases and 314 controls completed the baseline questionnaire and could be matched with clinical data. For regression models, we restricted cases to those with HCV diagnosed since 2018 (N = 100). Factors independently associated with case status included sex-associated rectal bleeding, shared fisting lubricant, anal douching, chemsex, intravenous and intracavernosal injections, with population-attributable fractions of 88% (model 1) and 85% (model 2). These factors remained stable over time among cases, while sexual partner numbers and group sex decreased during COVID-19 measures., Conclusions: Sexual/sex-associated practices leading to blood exposure are key factors in HCV transmission in MSM. Public health interventions should emphasize the importance of blood safety in sexual encounters. Micro-elimination efforts were temporarily aided by reduced opportunities for sexual encounters during the COVID-19 pandemic., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Introduction and Aim: Radiotherapy in cancer patients with a pacemaker or an implantable cardioverter defibrillator might damage the device and possibly result in malfunction of the device. We aimed to examine device malfunction and change in lead parameters in this group., Methods: The medical records of pacemaker/implantable cardioverter defibrillator patients who underwent radiotherapy at Aalborg University Hospital between July 1, 2016, and June 30, 2021, were reviewed. Treatment was planned according to risk of device malfunction, assessed using local guidelines. Bootstrap linear regression was used to identify possible differences in lead parameters depending on beam energy and anatomical location., Results: One hundred nine patients with a pacemaker/implantable cardioverter defibrillator who received a total of 122 radiotherapy courses in the study period were identified. No device malfunctions or significant changes in lead parameters during radiotherapy were observed. Only the left ventricle lead threshold and impedance were found to be significantly different when compared by beam energy; however, these changes were relatively small and unlikely to be of clinical relevance., Conclusion: No device malfunction or clinically relevant changes in lead parameters were identified in this study, suggesting that radiotherapy of pacemaker/implantable cardioverter defibrillator patients can be regarded as safe when following relevant safety precautions., (© 2024 The Author(s). Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background: Obesity and type 2 diabetes mellitus (T2DM) are increasingly common in the United States and worldwide. Because both conditions are associated with serious health consequences, weight reduction is recommended by professional medical and nutrition societies to improve outcomes. Due to the striking efficacy of glucagon-like peptide receptor agonists (GLP-1RAs) and dual mechanism glucose-dependent insulinotropic polypeptide/glucagon-like peptide receptor agonists (GIP/GLP-1RAs) for weight reduction and glycemic control, there is increased utilization for patients with obesity and/or T2DM. Yet, the impact of these medications on dietary intake is less understood., Methods: This narrative literature review summarizes clinical studies quantifying and characterizing dietary intake in people with obesity and/or T2DM using GLP-1 or GIP/GLP-1 RAs., Results: Though data from these studies reveal that total caloric intake was reduced by 16-39 %, few studies evaluated the actual composition of the diet., Conclusions: Further research is needed to understand the unique nutritional needs of adults on GLP-1 or dual GIP/GLP-1RAs and to support the development of nutritional guidelines for these individuals., Competing Interests: All the authors listed have approved the manuscript and have no conflicts of interest on this paper. KR, ST, and DW are employees and stockholders of Abbott (Abbott Park, IL, USA)., (© 2024 The Authors. Published by Elsevier Inc. on behalf of Obesity Medicine Association.)

Background: Omega-3 fatty acids derived from seafood acids may influence cardiac arrhythmogenesis, whereas the role of the major plant-derived omega-3 fatty acid, alpha-linolenic acid (ALA), on atrial fibrillation (AF) is largely unknown., Objectives: We aimed to investigate the association between ALA intake and risk of incident AF overall and in subjects with a low intake of marine omega-3 fatty acids., Methods: We followed a total of 54,260 middle-aged men and women enrolled into the Danish Diet, Cancer, and Health cohort for development of AF using nationwide registries. Intake of ALA was assessed using a validated food frequency questionnaire and modeled as a restricted cubic spline. Statistical analyses were conducted using Cox proportional hazards regression., Results: We identified a total of 4902 incident AF events during a median of 16.9 y of follow-up. In multivariable analyses, we observed indications of a statistically nonsignificant inverse association between ALA intake and risk of AF up to an ALA intake of 2.5 g/d, whereas no appreciable association was found for higher intakes of ALA. A statistically significant dose-dependent negative association was found between ALA intake and risk of AF in individuals consuming < 250 mg marine omega-3 fatty acids daily, whereas no association was found in those with a higher intake of marine omega-3 fatty acids., Conclusions: Intake of ALA was associated with a lower risk of AF in individuals consuming a low intake of marine omega-3 fatty acids. This finding is novel and warrants further investigation., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background CT perfusion (CTP)-derived baseline ischemic core volume (ICV) can overestimate the true extent of infarction, which may result in exclusion of patients with ischemic stroke from endovascular treatment (EVT). Purpose To determine whether ischemic core overestimation is associated with larger ICV and degree of recanalization. Materials and Methods This retrospective multicenter cohort study included patients with acute ischemic stroke triaged at multimodal CT who underwent EVT between January 2015 and January 2022. The primary outcome was ischemic core overestimation, which was assumed when baseline CTP-derived ICV was larger than the final infarct volume at follow-up imaging. The secondary outcome was functional independence defined as modified Rankin Scale scores of 0-2 90 days after EVT. Successful vessel recanalization was defined as extended Thrombolysis in Cerebral Infarction score of 2b or higher. Categorical variables were compared between patients with ICV of 50 mL or less versus large ICV greater than 50 mL with use of the χ 2 test. Adjusted multivariable logistic regression analyses were used to assess the primary and secondary outcomes. Results In total, 721 patients (median age, 76 years [IQR, 64-83 years]; 371 female) were included, of which 162 (22%) demonstrated ischemic core overestimation. Core overestimation occurred more often in patients with ICV greater than 50 mL versus 50 mL or less (48% vs 16%; P < .001) and those with successful versus unsuccessful vessel recanalization (26% vs 13%; P < .001). In an adjusted model, successful recanalization after EVT (odds ratio [OR], 3.14 [95% CI: 1.65, 5.95]; P < .001) and larger ICV (OR, 1.03 [95% CI: 1.02, 1.04]; P < .001) were independently associated with core overestimation, while the time from symptom onset to imaging showed no association (OR, 0.99; P = .96). Core overestimation was independently associated with functional independence (adjusted OR, 2.83 [95% CI: 1.66, 4.81]; P < .001) after successful recanalization. Conclusion Ischemic core overestimation occurred more frequently in patients presenting with large CTP-derived ICV and successful vessel recanalization compared with those with unsuccessful recanalization. © RSNA, 2024 Supplemental material is available for this article.

Disease co-occurrence in wildlife populations is common yet understudied. In the case of disease-caused mortality, the mortality attributed to one disease has the potential to buffer populations against subsequent alternative disease outbreaks by reducing populations and thus contacts needed to sustain disease transmission. However, substantial disease-driven population declines may also prevent populations from recovering, leading to localized extinctions. Hemorrhagic disease (HD), a vector-transmitted, viral disease in white-tailed deer (WTD), similar to chronic wasting disease (CWD), a prion disease, has increased in frequency and distribution in the United States. However, unlike CWD, which progresses slowly, HD can cause mortality only days after infection. Hemorrhagic disease outbreaks can result in substantial localized mortality events in WTD near vector habitats such as wetlands and may reduce local deer densities and consequent CWD transmission. The objective of our study was to evaluate the potential for HD outbreaks to buffer CWD risk where the diseases co-occur. Using an agent-based modeling approach, we found that frequent, intense HD outbreaks have the potential to mitigate CWD risk, especially if those outbreaks occur shortly after CWD introduction. However, HD outbreaks that do not result in substantial WTD mortality are unlikely to impact CWD or WTD population dynamics. Severe HD outbreaks may reduce CWD cases and could present an opportunity for managers to boost CWD control initiatives in a post-HD outbreak year.

Background: Prone position ventilation (PPV) is recommended for patients with COVID-19 induced severe Adult Respiratory Distress Syndrome (ARDS) and is used for patients supported with V-V ECMO as well. The purpose of this study was to describe the use of PPV in these patients focusing on physiological effects with the hypothesis that PPV could reduce oxygen need and improve dynamic compliance., Methods: This study was a nationwide retrospective analysis of all COVID-19 patients in Denmark from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. Data on the number of patients treated with PPV, number of PPV sessions, timing, the time spent in prone position, pulmonary physiological response types with analysis of variables affecting the response are reported., Results: Out of 68 patients 44 were treated with 220 PPV sessions and a positive clinical response was observed in 80% of patients but only in 45% of sessions. On a single session level, increased compliance was observed in 38% and increased oxygenation in only 15% of 220 sessions, with within-patient heterogeneity. Higher dynamic compliance at the beginning of a PPV session was associated with a lower delta change in dynamic compliance during PPV. The response to a PPV session could not be predicted by the response in the prior session. Dynamic compliance did not change during the ECMO course., Conclusion: Eighty percent of patients responded positively during a PPV session, but this was not associated with overall pulmonary improvement. On a single patient level, responses were heterogenous and only 45% of sessions resulted in clinical improvement. Response in dynamic compliance was associated with starting values of compliance., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: Invasive mechanical ventilation (IMV) is widely used in patients with cardiogenic shock following acute myocardial infarction (AMICS), but evidence to guide practice remains sparse. We sought to evaluate trends in the rate of IMV utilization, applied settings, and short term-outcome of a contemporary cohort of AMICS patients treated with IMV according to out-of-hospital cardiac arrest (OHCA) at admission., Methods: Consecutive AMICS patients receiving IMV in an intensive care unit (ICU) at two tertiary centres between 2010 and 2017. Data were analysed in relation to OHCA., Results: A total of 1274 mechanically ventilated AMICS patients were identified, 682 (54%) with OHCA. Frequency of IMV increased during the study period, primarily due to higher occurrence of OHCA admissions. Among 566 patients with complete ventilator data, positive-end-expiratory pressure, inspired oxygen fraction, and minute ventilation during the initial 24 h in ICU were monitored. No differences were observed between 30-day survivors and non-survivors with OHCA. In non-OHCA, these ventilator requirements were significantly higher among 30-day non-survivors (P for all<0.05), accompanied by a lower PaO2/FiO2 ratio (median 143 vs. 230, P < 0.001) and higher arterial lactate levels (median 3.5 vs. 1.5 mmol/L, P < 0.001) than survivors. Physiologically normal PaO2 and pCO2 levels were achieved in all patients irrespective of 30-day survival and OHCA status., Conclusion: In the present contemporary cohort of AMICS patients, physiologically normal blood gas values were achieved both in OHCA and non-OHCA in the early phase of admission. However, increased demand of ventilatory support was associated with poorer survival only in non-OHCA patients., Competing Interests: Declaration of Competing Interest Dr Christian Hassager received research grants from the Lundbeck Foundation(R186-2015-2132), the Novo Nordisk Foundation (NNF20OC0064043), and the Danish Heart Foundation (21-R151-A10091-22200). Dr Jacob Eifer Møller received an institutional research grant from Abiomed and Novo Nordic Foundation. Speakers' fees were received from Abbott, Abiomed, and Boehringer Ingelheim. The remaining authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In recent years, there has been an intense debate about how learning in biological neural networks (BNNs) differs from learning in artificial neural networks. It is often argued that the updating of connections in the brain relies only on local information, and therefore a stochastic gradient-descent type optimization method cannot be used. In this note, we study a stochastic model for supervised learning in BNNs. We show that a (continuous) gradient step occurs approximately when each learning opportunity is processed by many local updates. This result suggests that stochastic gradient descent may indeed play a role in optimizing BNNs., (© 2024 Massachusetts Institute of Technology.)

Background: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes., Methods: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis., Results: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; P trend <0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; P trend <0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization., Conclusions: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes., Competing Interests: Disclosures Dr Wouters reports grants from Remmert Adriaan-Laan-Fonds. Dr Arquizan reports compensation from Amgen and Medtronic Vascular, Inc, for other services. Dr Christensen reports stock holdings in iSchemaView. Dr Costalat reports compensation from Penumbra, Inc, MicroVention, Inc, Balt USA, LLC, Stryker Corporation, Medtronic USA, Inc, and Johnson & Johnson Health Care Systems, Inc, for consultant services. Dr Heit reports consulting fees from Medtronic and MicroVention, and he is a member of the Medical and Scientific Advisory Board of iSchemaView. Dr Albers reports stock holdings in iSchemaView and compensation from Biogen, iSchemaView, and Genentech for consultant services. The other authors report no conflicts.

Background: Timely diagnosis of acute intestinal necrosis (AIN) is lifesaving, but challenging due to unclear clinical presentation. D-lactate has been proposed as an AIN biomarker., Objectives: We aimed to test the diagnostic performance in a clinical setting., Methods: We performed a cross-sectional prospective study, including all adult patients with acute referral to a single tertiary gastrointestinal surgical department during 2015-2016 and supplemented by enrollment of high-risk in-hospital patients suspected of having AIN during 2016-2019. AIN was verified intraoperatively, and D-lactate was analyzed using an automatic spectrophotometric set-up. A D-lactate cut-off for AIN was estimated using the receiver operating characteristic curve. The performance according to patient subgroups was estimated using the area under the receiver operating characteristic curve (AUC). Given the exploratory nature of this study, a formal power calculation was not feasible., Results: Forty-four AIN patients and 2914 controls were enrolled. The D-lactate cut-off was found to be 0.0925 mM. Due to lipemic interference, D-lactate could not be quantified in half of the patients, leaving 23 AIN patients and 1456 controls for analysis. The AUC for the diagnosis of AIN by D-lactate was 0.588 (95% confidence interval 0.475-0.712), with a sensitivity of 0.261 and specificity of 0.892. Analysis of high-risk patients showed similar results (AUC 0.579; 95% confidence interval 0.422-0.736)., Conclusion: D-lactate showed low sensitivity for AIN in both average-risk and high-risk patients. Moreover, lipemic interference precluded valid spectrophotometric assessment of D-lactate in half of the patients, further disqualifying the clinical utility of D-lactate as a diagnostic marker for AIN., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: A key element of advance care planning (ACP) is the goals of care (GOC) conversation between the provider and the patient. The value of meaningful GOC conversations for the patient, provider, and health care institution is well documented. However, if the GOC documentation is buried in the medical record, not well defined, or poorly documented, that value is squandered. The Improvement Process: Interventions were implemented with oncology physicians and nurse practitioners (NPs). These included education, system reform including improving the ease and consistency of documentation of ACP, and regular feedback. Results: Participants reported increased confidence in communication skills about GOC conversations postworkshops. Data results for the tracked metrics, health care power of attorney, code status, and GOC, all showed improvement. Conclusion: Physicians and NPs recognized the importance of GOC conversations as part of ACP. Considerable progress was made by focusing on GOC conversations, maximizing information technology, participating in coaching, and ongoing data monitoring.

Recurrent glioblastoma (rGBM) remains a major unmet medical need, with a median overall survival of less than 1 year. Here we report the first six patients with rGBM treated in a phase 1 trial of intrathecally delivered bivalent chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor (EGFR) and interleukin-13 receptor alpha 2 (IL13Rα2). The study's primary endpoints were safety and determination of the maximum tolerated dose. Secondary endpoints reported in this interim analysis include the frequency of manufacturing failures and objective radiographic response (ORR) according to modified Response Assessment in Neuro-Oncology criteria. All six patients had progressive, multifocal disease at the time of treatment. In both dose level 1 (1 ×10 7 cells; n = 3) and dose level 2 (2.5 × 10 7 cells; n = 3), administration of CART-EGFR-IL13Rα2 cells was associated with early-onset neurotoxicity, most consistent with immune effector cell-associated neurotoxicity syndrome (ICANS), and managed with high-dose dexamethasone and anakinra (anti-IL1R). One patient in dose level 2 experienced a dose-limiting toxicity (grade 3 anorexia, generalized muscle weakness and fatigue). Reductions in enhancement and tumor size at early magnetic resonance imaging timepoints were observed in all six patients; however, none met criteria for ORR. In exploratory endpoint analyses, substantial CAR T cell abundance and cytokine release in the cerebrospinal fluid were detected in all six patients. Taken together, these first-in-human data demonstrate the preliminary safety and bioactivity of CART-EGFR-IL13Rα2 cells in rGBM. An encouraging early efficacy signal was also detected and requires confirmation with additional patients and longer follow-up time. ClinicalTrials.gov identifier: NCT05168423 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

During the last two decades, several cases of venous thrombosis (VTE) after a prolonged period at a computer have been described, denominated as "eThrombosis". Video gaming on a computer has become very popular and can be a social activity where several players gather to play against each other or in a virtual environment for several days ("LAN (i.e., L ocal A rea N etwork) parties") where the participants are sedentary and consuming calorie-rich food items. The aim of this study was to investigate potential coagulation activation during a 42 h LAN party. Nine male gamers volunteered for the LAN party. Citrated blood was sampled before and every 6 h, and plasma was analyzed for thrombin generation, thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and D-dimer. Thrombin generation increased slightly but not significantly during the LAN party, whereas the coagulation activation markers were unchanged. These results do not indicate that the coagulation system is activated significantly during 42 h of gaming with minimal physical activity. Although increased activity cannot be excluded, it does not directly indicate a risk of VTE in general., Competing Interests: The authors declare no conflicts of interest.

Background: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear., Methods: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation., Results: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09)., Conclusions: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.)., (Copyright © 2024 Massachusetts Medical Society.)

The field of personalized medicine (PM) has grown rapidly because of the "omics revolution", but PM may be difficult for patients to comprehend. This study sought to explore head and neck cancer (HNC) patients' positions and knowledge of PM, gene tests, and follow-up and to compare HNC patients' positions to a sample from a national Danish questionnaire. To do this, patients with prior HNC were invited to participate in a questionnaire. Initial interviews revealed a heterogenic understanding of PM between patients. A total of 226 patients were included in the survey and 177 patients with complete data were included for analysis. Most patients were more positive than negative towards gene tests and gene research (83% and 93%, respectively), but 72% had little or no knowledge of the subject. Almost all patients, 98%, were satisfied with their follow-up. Significantly more patients with HNC were positive towards gene research compared to a sample from a national Danish questionnaire ( p < 0.001). Patients with HNC were positive towards gene tests and PM, but patients may not understand or comprehend the information given, and it is important to inform and educate patients and health professionals to establish common ground in PM.

Background: Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN., Methods: The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy., Discussion: If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival., Trial Registration: ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25 th . 2023., (© 2024. The Author(s).)

Chronic wasting disease (CWD) is a prion disease affecting cervid species, both free-ranging and captive populations. As the geographic range continues to expand and disease prevalence continues to increase, CWD will have an impact on cervid populations, local economies, and ecosystem health. Mitigation of this "wicked" disease will require input from many different stakeholders including hunters, landowners, research biologists, wildlife managers, and others, working together. The NC1209 (North American interdisciplinary chronic wasting disease research consortium) is composed of scientists from different disciplines involved with investigating and managing CWD. Leveraging this broad breadth of expertise, the Consortium has created a state-of-the-science review of five key aspects of CWD, including current diagnostic capabilities for detecting prions, requirements for validating these diagnostics, the role of environmental transmission in CWD dynamics, and potential zoonotic risks associated with CWD. The goal of this review is to increase stakeholders', managers', and decision-makers' understanding of this disease informed by current scientific knowledge.

In some places, N 2 O emissions have doubled during the last 2-3 decades. Therefore, it is crucial to identify N 2 O emission hotspots from terrestrial and aquatic systems. Large variation in N 2 O emissions occur in managed as well as in natural areas. Natural unmanaged tropical and subtropical wet forests are important N 2 O sources globally. Emission hotspots, often coupled to human activities, vary across climate zones, whereas N 2 O emissions are most often a few kg N ha -1 year -1 from arable soils, drained organic soils in the boreal and temperate zones often release 20-30 kg N ha -1 year -1 . Similar high N 2 O emissions occur from some tropical crops like tea, palm oil and bamboo. This strong link between increased N 2 O emissions and human activities highlight the potential to mitigate large emissions. In contrast, water where oxic and anoxic conditions meet are N 2 O emission hotspots as well, but not possible to reduce., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment., Methods: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry., Findings: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes., Interpretation: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles., Competing Interests: Competing interests: DP and Dr EL are members of the Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resources Evaluation management committee. AB is funded by Wellcome. JS and MS are cofounders and shareholders of Epimed Solutions, a healthcare cloud-based analytics company. They are also supported in part by individual research grants from CNPq and FAPERJ. SB is the current chair, and MR is the past chair of the Finnish Intensive Care Consortium (both unpaid). DAD is unpaid chair of NICE foundation. NI's primary affiliation is the Department of Healthcare Quality Assessment, which is a social collaboration department at the University of Tokyo supported by National Clinical Database, Johnson & Johnson K.K., and Nipro corporation. BKTV is the National Coordinator for the Indian Registry of IntenSive care (IRIS) and is supported for 0.5 FTE by funding from the Wellcome Trust, UK. The remaining authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The use of lentiviral vectors in cell and gene therapy is steadily increasing, both in commercial and investigational therapies. Although existing data increasingly support the usefulness and safety of clinical-grade lentiviral vectors used in cell manufacturing, comprehensive studies specifically addressing their long-term stability are currently lacking. This is significant considering the high cost of producing and testing GMP-grade vectors, the limited number of production facilities, and lengthy queue for production slots. Therefore, an extended shelf life is a critical attribute to justify the investment in large vector lots for investigational cell therapies. This study offers a thorough examination of essential stability attributes, including vector titer, transduction efficiency, and potency for a series of clinical-grade vector lots, each assessed at a minimum of 36 months following their date of manufacture. The 13 vector lots included in this study were used for cell product manufacturing in 16 different clinical trials, and at the time of the analysis had a maximum storage time at -80°C of up to 8 years. The results emphasize the long-term durability and efficacy of GMP-grade lentiviral vectors for use in ex vivo cell therapy manufacturing., Competing Interests: C.H.J is an inventor on patents and/or patent applications licensed to Novartis Institutes of Biomedical Research and receives license revenue from such licenses. C.H.J. is a scientific cofounder of Capstan Therapeutics, Bluewhale Bio, and Tceleron; is a consultant to Kite Pharma; and is a member of the Scientific Advisory Boards of AC Immune, Alaunos, BluesphereBio, Cabaletta, Carisma, Cartography Biosciences, Cellares, Celldex, Decheng, Poseida, Replay Bio, Verismo, and WIRB-Copernicus Group. A.C. is a scientific cofounder of Tceleron, and is a consultant to Kite Pharma and Bluewhale Bio. J.A.F. has received grants and personal fees from Cartography Biosciences, grants from Tmunity Therapeutics, and personal fees from Retro Bio and Shennon Bio outside the submitted work. In addition, J.A.F. holds patents related to CAR T cells for cancer that are licensed and associated with royalties., (© 2024 The Author(s).)

Ice hockey is a high-risk sport known for its dominant macho culture. The purpose of this study was to examine experiences surrounding medication use among male, elite ice hockey players in Norway. A mixed-method design was employed, which first examined medications registered on doping control forms (DCFs) ( n = 177) and then involved semi-structured focus group interviews ( n = 5) with elite athletes ( n = 25). Overall, 68% of the DCFs contained information about ≥1 medication. Among the most registered medications were NSAIDs and hypnotics (20% and 19% of all DCFs, respectively). During the interviews, numerous athletes reported using analgesics to manage injuries and pain caused by the sport, often being motivated by sacrificing themselves for the team during important matches and playoffs. Hypnotics were used due to high cumulative stress due to heavy training and competition load, late-night matches, and playing in a semi-professional league. Athlete support personnel (ASP), including physicians and trainers, were the athletes' main sources of information. The athletes often displayed a profound and non-critical trust in the advice and products provided to them by their team physician. The findings indicate that male, elite ice hockey players, through their excessive and somewhat ignorant use of medications, expose themselves to health risks and inadvertent doping.

Background: In Denmark, stroke represents a leading disability cause. While people with difficulties in performing activities of daily living (ADL) due to poststroke cognitive impairments are often referred to occupational therapy, limited knowledge is available on the nature of these services., Aim/objective: To explore how Danish occupational therapists describe their practice when addressing decreased ADL ability in people with poststroke cognitive impairments in hospital and municipality settings., Material and Methods: National, cross-sectorial, web-based public survey., Results: 244 occupational therapists accessed the survey; 172 were included in the analysis. Most respondents could indicate the theory guiding their reasoning; half used standardised assessments. Regarding intervention, restorative and acquisitional models were preferred; specific strategies were identified. Intensity: 30-45 min 3-4 times/week in hospitals; 30-60 min 1-2 times/week in municipalities., Conclusions: Therapists report to be guided by theory in their reasoning. Standardised assessments are used to a higher extend than previously reported. Still, the results invite critical reflections on correct use of assessment instruments, content and intensity of interventions, and how therapists keep themselves updated., Significance: The results document the need for practice improvements and may inform the definition of standard care in future trials.

Background: X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital muscle disease caused by mutations in the MTM1 gene that result in profound muscle weakness, significant respiratory insufficiency, and high infant mortality. There is no approved disease-modifying therapy for XLMTM. Resamirigene bilparvovec (AT132; rAAV8-Des-hMTM1) is an investigational adeno-associated virus (AAV8)-mediated gene replacement therapy designed to deliver MTM1 to skeletal muscle cells and achieve long-term correction of XLMTM-related muscle pathology. The clinical trial ASPIRO (NCT03199469) investigating resamirigene bilparvovec in XLMTM is currently paused while the risk:benefit balance associated with this gene therapy is further investigated., Methods: Muscle biopsies were taken before treatment and 24 and 48 weeks after treatment from ten boys with XLMTM in a clinical trial of resamirigene bilparvovec (ASPIRO; NCT03199469). Comprehensive histopathological analysis was performed., Findings: Baseline biopsies uniformly showed findings characteristic of XLMTM, including small myofibres, increased internal or central nucleation, and central aggregates of organelles. Biopsies taken at 24 weeks post-treatment showed marked improvement of organelle localisation, without apparent increases in myofibre size in most participants. Biopsies taken at 48 weeks, however, did show statistically significant increases in myofibre size in all nine biopsies evaluated at this timepoint. Histopathological endpoints that did not demonstrate statistically significant changes with treatment included the degree of internal/central nucleation, numbers of triad structures, fibre type distributions, and numbers of satellite cells. Limited (predominantly mild) treatment-associated inflammatory changes were seen in biopsy specimens from five participants., Interpretation: Muscle biopsies from individuals with XLMTM treated with resamirigene bilparvovec display statistically significant improvement in organelle localisation and myofibre size during a period of substantial improvements in muscle strength and respiratory function. This study identifies valuable histological endpoints for tracking treatment-related gains with resamirigene bilparvovec, as well as endpoints that did not show strong correlation with clinical improvement in this human study., Funding: Astellas Gene Therapies (formerly Audentes Therapeutics, Inc.)., Competing Interests: Declaration of interests MWL has received research funding from Astellas Gene Therapies∗ to his academic institution (Medical College of Wisconsin) and to his company (Diverge Translational Science Laboratory) for work related to the present manuscript; has received research grants or contracts to his academic institution (Medical College of Wisconsin) from Solid Biosciences, Kate Therapeutics, Taysha Therapeutics, Ultragenyx, and Prothelia; has received consulting fees from Astellas Gene Therapies∗, Encoded Therapeutics, Modis Therapeutics, Lacerta Therapeutics, AGADA Biosciences, Dynacure, Affinia, Voyager, BioMarin, Locanabio, and Vertex Pharmaceuticals; has received speaker fees and reimbursement for travel related to sponsored research from Astellas Gene Therapies∗; has received personal fees for scientific advisory board participation for Astellas Gene Therapies∗ and Solid Biosciences, and his institution has received payment from Taysha Therapeutics for his advisory board participation; he is currently CEO, founder, and owner of Diverge Translational Science Laboratory, which continues to work under contracts from many gene therapy companies including Astellas Gene Therapies∗, Solid Biosciences, Rocket Pharma, Kate Therapeutics, Carbon Biosciences, Dynacure, Nationwide Children's Hospital, Taysha Gene Therapies, and Ultragenyx. BS (Schoser) has received grants/contracts, honoraria, and support for attending meetings from Astellas Gene Therapies∗ has participated in Advisory Boards for Dynacure. MM has received personal fees and study funding to her institution from Astellas Gene Therapies∗ in relation to the present manuscript. CAS has received royalties from Elsevier for the book “Muscle Biopsy. A Practical Approach”. KAJ has received consulting fees from Astellas Gene Therapies∗ in relation to the present manuscript and other activities. PBS has received research funding from Astellas Gene Therapies∗ to support clinical trial investigations relating to the present manuscript; has received research contracts from Biogen, Dyne, Fulcrum, Pfizer, PTC Therapeutics, Reveragen, Sanofi, Sarepta, and Solid Biosciences; has received consulting fees from Alexion, Argenx, Biogen, Novartis Gene Therapies, Pfizer, UCB, and Sarepta; has received honoraria for lectures or presentations from Alexion, Argenx, Biogen, Catalyst, CSL Behring, Genentech, and Grifols; and has participated on Independent Data Monitoring Committees for Encoded Therapeutics, Excision BioTherapeutics, and Taysha. NLK reports research grants paid to her institution from AMO Pharma, Argenx, Astellas Gene Therapies∗, Biogen, Biohaven, Novartis, NS Pharma, Sarepta, Reveragen, Roche, and Scholar Rock; has received payment for educational presentations from Sarepta; and has participated in a Data Safety Monitoring Board for Sarepta and Advisory Boards for Argenx, BioMarin, Fibrogen, Roche, and Sarepta. BKS has received institutional research grants or contracts to serve as an INCEPTUS and ASPIRO study site from Astellas Gene Therapies∗. JJD has received research grants from NIH, CIHR, and Astellas Gene Therapies∗; has received support for attending annual meetings from the World Muscle Society (as Executive Board Member) and TREAT NMD (as Chair of Executive Board); and receives annual honoraria as a Scientific Advisory Board member for the RYR1 Foundation. WMF has received support for study materials and study personnel relating to the present manuscript from Astellas Gene Therapies∗; consulting fees from Sarepta, PTC Therapeutics, Novartis, and Roche; personal compensation from Novartis and Biogen, and institutional funding from Roche, for lectures; and has served on Scientific Advisory Boards for DGM and Glykogenosis e.V. CGB reports study funding relating to the present manuscript paid to NINDS; and has participated in data safety monitoring or advisory boards without financial compensation, in his capacity of representing NIH. AMS is a principal investigator in the ASPIRO study. AB has received speaker's honoraria from Pfizer and Roche; and has participated in advisory boards at for Pfizer and Roche. SN, ARF, DNS, ET, and URQ report no conflicts of interests. MB and MJP are full-time employees of Diverge Translational Science Laboratory. EO and SD report no conflicts of interest. PK is a full-time employee of Diverge Translational Science Laboratory. SNK report no conflicts of interest. HM is a full-time employee of Diverge Translational Science Laboratory. MVA, CW, and HGD report no conflicts of interest. AHB received study funding relating to the present manuscript; reports grants or contracts received from NIH, MDA (USA), and the Chan Zuckerberg Initiative, and from AFM Telethon, Alexion Pharmaceuticals Inc., Avidity, Dynacure SAS, Kate Therapeutics, and Pfizer Inc. He has received consulting fees from Astellas Gene Therapies∗, Dynacure, GLG Inc., Guidepoint Global, Kate Therapeutics, and Roche; has received support for attending meetings from Kate Therapeutics and MDA; holds equity in Kate Therapeutics and Kinea Bio, and is an inventor on a US patent describing a method for gene therapy of XLMTM. SC, EC, JL, CS, WM, BS (Sepulveda), FV are former employees of Astellas Gene Therapies∗. ESJ and SR are former employees and stockholders in Astellas Gene Therapies∗. SP was Chief Medical Officer and a stockholder in Astellas Gene Therapies∗ when the study was designed and initiated; he is no longer a stockholder and currently consults independently with a wide variety of companies and academic institutions primarily on Clinical Development matters. ∗Formerly Audentes Therapeutics, Inc., (Copyright © 2023. Published by Elsevier B.V.)