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Environmental exposures and community characteristics have been linked to accelerated lung function decline in people with cystic fibrosis (CF), but geomarkers, the measurements of these exposures, have not been comprehensively evaluated in a single study. To determine which geomarkers have the greatest predictive potential for lung function decline and pulmonary exacerbation (PEx), a retrospective longitudinal cohort study was performed using novel Bayesian joint covariate selection methods, which were compared with respect to PEx predictive accuracy. Non-stationary Gaussian linear mixed effects models were fitted to data from 151 CF patients aged 6-20 receiving care at a CF Center in the midwestern US (2007-2017). The outcome was forced expiratory volume in 1 s of percent predicted (FEV1pp). Target functions were used to predict PEx from established criteria. Covariates included 11 routinely collected clinical/demographic characteristics and 45 geomarkers comprising 8 categories. Unique covariate selections via four Bayesian penalized regression models (elastic-net, adaptive lasso, ridge, and lasso) were evaluated at both 95 % and 90 % credible intervals (CIs). Resultant models included one to 6 geomarkers (air temperature, percentage of tertiary roads outside urban areas, percentage of impervious nonroad outside urban areas, fine atmospheric particulate matter, fraction achieving high school graduation, and motor vehicle theft) representing weather, impervious descriptor, air pollution, socioeconomic status, and crime categories. Adaptive lasso had the lowest information criteria. For PEx predictive accuracy, covariate selection from the 95 % CI elastic-net had the highest area under the receiver-operating characteristic curve (mean ± standard deviation; 0.780 ± 0.026) along with the 95 % CI ridge and lasso methods (0.780 ± 0.027). The 95 % CI elastic-net had the highest sensitivity (0.773 ± 0.083) while the 95 % CI adaptive lasso had the highest specificity (0.691 ± 0.087), suggesting the need for different geomarker sets depending on monitoring goals. Surveillance of certain geomarkers embedded in prediction algorithms can be used in real-time warning systems for PEx onset., 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 © 2024 Elsevier B.V. All rights reserved.)

The postnatal environment is challenging for the preterm neonate with exposure to hypoxic and excitotoxic events, amplified by premature loss of placentally derived neurosteroids. Between preterm birth and term equivalent age (TEA), cerebellar development continues despite these challenges. We hypothesize that neurosteroid replacement therapy during this time will support optimal cerebellar development. Guinea pig sows delivered at term (∼69 days gestation) or were induced to deliver preterm (∼62 days), with preterm pups receiving ganaxolone or vehicle until TEA. Postnatal assessments comprised salivary cortisol (corrected postnatal age [CPA] 0, 7, 38), behavioral analysis (CPA7, 38), and tissue collection (CPA0 and CPA40). Neurodevelopmental markers (MBP, Olig2, and NeuN) were assessed in the cerebellum by immunohistochemistry, whereas RT-PCR was utilized to investigate key inhibitory/excitatory pathways and oligodendrocyte lineage markers. Following preterm birth, there was evidence of a hyperactive phenotype, increased salivary cortisol concentrations, and impaired myelination and oligodendrocyte maturation at the protein level. mRNA expressions of key inhibitory/excitatory pathways and myelin stability were also altered following preterm birth. Importantly, we showed that neurosteroid replacement therapy returns cerebellar development and behavior toward a term-like phenotype. Therefore, ganaxolone may reduce the vulnerability of the cerebellum to postnatal challenges arising from preterm birth., (© 2024 The Author(s). Developmental Psychobiology published by Wiley Periodicals LLC.)

Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions. This ACTION-ARC international expert panel of trialists, clinicians, patients, families, statisticians, biomedical engineers, device developers, and regulatory agencies drafted and iterated definitions harmonized to ACTION data and existing literature during sessions conducted between December 2022 and May 2023, followed by dissemination across clinical/research audiences and professional organizations and further revision. Both email-linked, internet-based surveys and in-person discussions were used as a modified Delphi process. Nineteen AE types were identified and defined, including seven new event types and six event types that were deleted and will no longer be collected, achieving consensus. ACTION-ARC paired rigorous development with methodical stakeholder involvement and dissemination to define pediatric VAD AEs to facilitate assimilation of data across future clinical trials and evaluation of devices for VAD-supported children and adults with CHD., Competing Interests: Disclosure: A.L. is a consultant for Bayer, Abbott, Abiomed, Berlin Heart, and Syncardia and is the primary investigator for the Berlin ACTIVE driver trial. I.A. is a consultant for Abbott, Abiomed, Bivacor, and Berlin Heart. P.M.A.A. is Treasurer of the Board of Directors of the Extracorporeal Life Support Organization (ELSO) and immediate past-chair of PediECMO, a research collaborative between ELSO and the Pediatric Acute Lung Injury and Sepsis Investigators. P. Alexander’s institution received funding from the National Institutes of Health (NICHD R13HD104432) and the U.S. Department of Defense (U.S. DoD PRMRP Clinical Trial Award #W81XWH2210301). R.P.B. reports grants from the National Institutes of Health (NIH) R01 HL153519 and is a member of the Extracorporeal Life Support Organization (ELSO) Board of Directors. S.B. is a full-time employee of Abiomed, Inc. a part of Johnson and Johnson. K.B. is an Abbott employee. J.C. receives an unrestricted education grant—from Abbott and is a medical monitor for Pumpkin Trial. R.R.D. is a paid consultant for Abbott, Inc. and Abiomed, Inc. R.L.K. is an employee at Abbott, Inc. R.K. is an employee at Berlin Heart Inc. M.K. is involved in Grants & Consulting for Medtronic, Abbott Vascular, Johnson & Johnson, Boston Scientific, and Getinge. J.L. is a consultant for Abbott. D.L.S.M. is a consultant for Abbott Inc., Syncardia Inc., and Berlin Heart Inc. R.A.N. uses Berlin Heart of North America travel funds to attend the annual user’s group meeting. F.D.P. is a non-compensated ad-hoc scientific advisor for Abbott, BrioHealth Solutions, FineHeart, and Medtronic, a non-compensated medical monitor for Abiomed, a member—Data Safety Monitoring Board for Carmat, receives grant funding from the National Heart, Lung, and Blood Institute and the Agency for Healthcare Research and Quality, and receives partial salary support from Blue Cross/Blue Shield of Michigan as Associate Director of the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. D.M.P. is on the Data Safety Monitoring Board for the Berlin Active Driver Trial. D.R. is associated with ACTION, DSMB for Parexel (unrelated to topic of AE manuscript), and Medicolegal consultation (unrelated to topic of AE manuscript). J.W.R. is a consultant for American Regent, AskBio, BioMarin, Bayer, Merck, Bristol Myers Squibb, and Enzyvant. E.S. reports institutional contracts for which he receives no direct compensation with Boston Scientific, Cardiawave, Edwards Lifesciences, Medtronic, Shanghai Microport Medical Co. Ltd., NVT GmBH, Pie Medical Imaging, Siemens Healthcare GmBH. M.E.S. is involved in a Medtronic educational contract, Octapharma advisory panel, and NIH DSMB for PumpKIN trial (completed). J.M.T. is a Berlin Heart CEC member. C.V. is on the Merck scientific advisory committee and a consultant for Abiomed. C.R.V. is a consultant for PTC therapeutics (previous), Antisense (current), and Capricor (current). The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Harnessing the rich nonlinear dynamics of highly deformable materials has the potential to unlock the next generation of functional smart materials and devices. However, unlocking such potential requires effective strategies to spatially engineer material architectures within the nonlinear dynamic regime. Here we introduce an inverse-design framework to discover flexible mechanical metamaterials with a target nonlinear dynamic response. The desired dynamic task is encoded via optimal tuning of the full-scale metamaterial geometry through an inverse-design approach powered by a fully differentiable simulation environment. By deploying such a strategy, mechanical metamaterials are tailored for energy focusing, energy splitting, dynamic protection and nonlinear motion conversion. Furthermore, our design framework can be expanded to automatically discover reprogrammable architectures capable of switching between different dynamic tasks. For instance, we encode two strongly competing tasks-energy focusing and dynamic protection-within a single architecture, using static precompression to switch between these behaviours. The discovered designs are physically realized and experimentally tested, demonstrating the robustness of the engineered tasks. Our approach opens an untapped avenue towards designer materials with tailored robotic-like reprogrammable functionalities., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

There are recognized neuroimaging regions of interest in typical Alzheimer's disease which have been used to track disease progression and aid prognostication. However, there is a need for validated baseline imaging markers to predict clinical decline in atypical Alzheimer's Disease. We aimed to address this need by producing models from baseline imaging features using penalized regression and evaluating their predictive performance on various clinical measures. Baseline multimodal imaging data, in combination with clinical testing data at two time points from 46 atypical Alzheimer's Disease patients with a diagnosis of logopenic progressive aphasia (N = 24) or posterior cortical atrophy (N = 22), were used to generate our models. An additional 15 patients (logopenic progressive aphasia = 7, posterior cortical atrophy = 8), whose data were not used in our original analysis, were used to test our models. Patients underwent MRI, FDG-PET and Tau-PET imaging and a full neurologic battery at two time points. The Schaefer functional atlas was used to extract network-based and regional gray matter volume or PET SUVR values from baseline imaging. Penalized regression (Elastic Net) was used to create models to predict scores on testing at Time 2 while controlling for baseline performance, education, age, and sex. In addition, we created models using clinical or Meta Region of Interested (ROI) data to serve as comparisons. We found the degree of baseline involvement on neuroimaging was predictive of future performance on cognitive testing while controlling for the above measures on all three imaging modalities. In many cases, model predictability improved with the addition of network-based neuroimaging data to clinical data. We also found our network-based models performed superiorly to the comparison models comprised of only clinical or a Meta ROI score. Creating predictive models from imaging studies at a baseline time point that are agnostic to clinical diagnosis as we have described could prove invaluable in both the clinical and research setting, particularly in the development and implementation of future disease modifying therapies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Matching avatar characteristics to a user can impact sense of embodiment (SoE) in YR. However, few studies have examined how participant demographics may interact with these matching effects. We recruited a diverse and racially balanced sample of 78 participants to investigate the differences among participant groups when embodying both demographically matched and unmatched avatars. We found that participant ethnicity emerged as a significant factor, with Asian and Black participants reporting lower total SoE compared to Hispanic participants. Furthermore, we found that user ethnicity significantly influences ownership (a subscale of SoE), with Asian and Black participants exhibiting stronger effects of matched avatar ethnicity compared to White participants. Additionally, Hispanic participants showed no significant differences, suggesting complex dynamics in ethnic-racial identity. Our results also reveal significant main effects of matched avatar ethnicity and gender on SoE, indicating the importance of considering these factors in VR experiences. These findings contribute valuable insights into understanding the complex dynamics shaping VR experiences across different demographic groups.

Objective: To describe characteristics associated with survival for pediatric patients with an oncologic diagnosis or hematopoietic cell transplant (HCT) supported with extracorporeal membrane oxygenation (ECMO)., Design: Multicenter, retrospective study., Setting: Sixteen PICUs in the United States and Israel., Patients: We included patients aged younger than 19 years with an oncologic diagnosis or HCT who required ECMO support between 2009 and 2021., Interventions: None., Measurements and Main Results: A total of 149 patients were included in the study cohort. There were 118 patients with an oncologic diagnosis and 31 that received HCT. The indications for ECMO were respiratory failure (46%), combined respiratory and cardiac failure (28%), and cardiac failure (25%). Venovenous (V-V) ECMO was used in 45% of patients, with 53% of patients being placed on venoarterial (V-A) ECMO. For oncologic and HCT groups, survival to ECMO decannulation was 52% (62/118) and 64% (20/31), and survival to hospital discharge was 36% (43/118) and 42% (13/31), respectively. After adjusting for other factors, requiring cardiopulmonary resuscitation was associated with greater odds ratio of mortality (3.0 [95% CI, 1.2-7.7])., Conclusions: Survival to ECMO decannulation of pediatric oncologic and HCT patients in this study was 52-64%, depending upon diagnosis. However, survival to hospital discharge remains poor. Future research should prioritize understanding factors contributing to this survival gap within these patient populations., Competing Interests: Dr. Mowrer received funding from the Extracorporeal Life Support Organization (ELSO). Drs. Nair and Potera’s institutions received funding from ELSO. Dr. Li disclosed work for hire. Dr. Barbaro’s institution received funding from the National Institutes of Health (NIH) (R01 HL153519); they disclosed they are a member of the ELSO Board of Directors and a member of pediatric extracorporeal membrane oxygenation (ECMO); they disclosed off-label use of ECMO. Dr. Barbaro is a board member for the ELSO and reports funding from the NIH (R01 HL153519). Dr. Zinter received support for article research from the NIH. Dr. Nkwantabisa received funding from Medtronic. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

As field-dispatchable power sources offer an alternative means of energy conversion, electrocatalyst development has become an area of intense focus. Emphasis has been placed on the transition from expensive electrocatalysts such as platinum and palladium toward earth abundant materials. Such a shift would result in lowered costs, enhanced durability, and an increased potential for implementation on a broader scale. High entropy oxides (HEOs) are an emerging class of materials that can offer both earth abundance and tunability of composition and morphology, making them excellent candidates for electrocatalysis. Several approaches have been taken to synthesize these materials and achieve balance between single-phase, highly crystalline products and high-surface area, nanostructured products. This work offers a survey of these methods, as well as our perspective on the most promising pathways forward. Emphasis is placed on clarifying the benefits, challenges, and overall suitability of each means of synthesis with electrocatalytic applications in mind.

Background: Dermatological presentations are common in primary care. The digital health space is growing in investment, revenue, and in usership numbers. Doctors utilise mobile health apps for referencing, communicating, and for clinical decision making. Dermabuddy is a secure mobile health app by which information and expertise around skin problems can be shared among a group of medical professionals with the aim of finding the best treatment and management plan., Aim: To assess the utility of the Dermabuddy health app for GPs and associated trainees in the Republic of Ireland., Design & Setting: This is a descriptive cross-sectional study, which involved a survey link distributed by email to GPs with Irish Medical Council membership., Method: GPs were surveyed on their experiences of using the dermatology mobile application, Dermabuddy., Results: In total, 203 members took this questionnaire (13.5% response rate). Ninety-six per cent who responded to the statement, 'The app was easy to use' , agreed it was 'easy' or 'very easy'. Eighty-seven per cent of those who responded to the statement, 'I would use this app again' , agreed they 'definitely would'. Fifty-eight per cent of those who responded to the statement, 'The app is useful for my healthcare practice' , gave it a five-star rating. The content of 36 comments included advice for improvement and positive feedback., Conclusion: The Dermabuddy app was well received by participants in this study. Across all sections of the questionnaire looking at aspects of the app, including ease of use, interface and satisfaction, and usefulness, there was a positive response. Mobile health apps, such as Dermabuddy, may provide alternative solutions to meet the rising challenge of managing patients with dermatological conditions in primary care., (Copyright © 2024, The Authors.)

Introduction: The influence of neighborhood characteristics and socioeconomic status (SES) factors on avoidable emergency department (ED) utilization is not well understood in a universal healthcare system. We examined correlations between these factors and avoidable ED visits at a Canadian academic hospital., Materials and Methods: We conducted a retrospective cohort study using administrative ED data from a hospital in Hamilton, Canada from April 1, 2018 to August 31, 2023, and neighborhood data from the Statistics Canada Census of Population 2021. Avoidable visits were classified using the Emergency Department Avoidability Classification (EDAC), and mapped to neighborhoods using Canadian postal codes. SES was defined primarily based on education attained, household income, employment and housing security. The top 20 postal codes with the highest avoidable ED visits were categorized into quartiles and analyzed for trends using chi-squared tests of spatial association and Spearman rank correlations., Results: A consistent ordinal trend across quartiles was observed throughout the study period, with quartile 1 representing the lowest avoidable ED visits and quartile 4 the highest. The quartiles were unevenly distributed spatially, though there was a significant association between close proximity to the ED and avoidable visits (X2 = 7.07, p <0.05). The quartile with the highest avoidable ED visits (quartile 4) had the greatest proportion of one-person households (35.5%) and one-parent families (37.8%), and showed statistically significant positive correlations with male sex, living alone and having an indigenous identity. Quartile 4 had the highest rates of individuals not completing high school (18.6%, p < 0.05), unemployment (13.7%), households spending greater than 30% of their income on shelter (26.5%), and households earning less than $30,000 annually (16.6%, compared to 8.7% in quartile 1 with the lowest avoidable ED visits)., Discussion: In a universal healthcare setting, lower SES neighborhoods were correlated with higher rates of avoidable ED visits. Targeted interventions that address social determinants of health disparities in neighborhoods with lower SES could reduce the burden of avoidable ED visits, and promote more equitable healthcare utilization., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Strum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: In patients with musculoskeletal (MSK) conditions, pain is the leading contributor to disability and significantly limits mobility and dexterity. This narrative review describes the efficacy and safety of topical analgesics in common use today., Evidence Acquisition: Secondary literature gained via a literature search using PubMed.gov and the Cochrane library were used., Study Design: Recent literature (2000-2023) on several major classes of topical analgesics and topical delivery systems were reviewed to provide strength of recommendation taxonomy (SORT) levels. A total of 86 articles were reviewed., Level of Evidence: Level 2., Results: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) and cabbage leaf wraps (CLW) appear to be best suited for multiple types of acute MSK pain, and topical nitroglycerin is helpful when used specifically for rotator cuff pain in patients seeking relief while performing activities of daily living and willing to treat for long periods of time. For compounded topical formulations, it may be better to offer single agent creams based on patient preferences. Little data support the use of cryotherapy. Traumeel could be a promising natural analgesic that compares with diclofenac. Topical lidocaine appears best suited for postherpetic neuropathic pain. O24 is a reasonable alternative with a low risk profile to treat pain in patients with fibromyalgia syndrome., Conclusion: Choice of topical agents should be guided by current evidence accounting for type of pain, medication side effects, patient comorbidities, as well as patient preference, convenience, and cost., Strength-Of-Recommendation Taxonomy (sort): Of the topical analgesics and modalities reviewed, SORT level A evidence was found for topical NSAID use in decreasing MSK pain, topical lidocaine for postherpetic neuralgia, and nitroglycerin patches for treating rotator cuff pain if used for prolonged periods of time. Alternative treatments such as CLW and Traumeel show promising results (SORT level B)., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Diterpenoid natural products serve critical functions in plant development and ecological adaptation and many diterpenoids have economic value as bioproducts. The family of class II diterpene synthases catalyzes the committed reactions in diterpenoid biosynthesis, converting a common geranylgeranyl diphosphate precursor into different bicyclic prenyl diphosphate scaffolds. Enzymatic rearrangement and modification of these precursors generates the diversity of bioactive diterpenoids. We report the crystal structure of Grindelia robusta 7,13-copalyl diphosphate synthase, GrTPS2, at 2.1 Å of resolution. GrTPS2 catalyzes the committed reaction in the biosynthesis of grindelic acid, which represents the signature metabolite in species of gumweed (Grindelia spp., Asteraceae). Grindelic acid has been explored as a potential source for drug leads and biofuel production. The GrTPS2 crystal structure adopts the conserved three-domain fold of class II diterpene synthases featuring a functional active site in the γβ-domain and a vestigial ɑ-domain. Substrate docking into the active site of the GrTPS2 apo protein structure predicted catalytic amino acids. Biochemical characterization of protein variants identified residues with impact on enzyme activity and catalytic specificity. Specifically, mutagenesis of Y457 provided mechanistic insight into the position-specific deprotonation of the intermediary carbocation to form the characteristic 7,13 double bond of 7,13-copalyl diphosphate., Competing Interests: Conflict of interest statement The authors declare no competing interests, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Clinical outcomes for patients with severe acute respiratory failure caused by different variants of the coronavirus disease 2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) are incompletely understood. Clinical characteristics, pre-ECMO management, and hospital mortality at 90 days for adults with COVID-19 who received venovenous ECMO (VV-ECMO) at North American centers during waves predominated by Delta (August 16 to December 12, 2021) and Omicron (January 31 to May 31, 2022) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were compared in a competing risks framework. One thousand seven hundred and sixty-six patients (1,580 Delta, 186 Omicron) received VV-ECMO for COVID-19 during the Delta- and Omicron-predominant waves in North American centers. In the unadjusted competing risks model, no significant difference was observed in risk of hospital mortality at 90 days between patients during the Delta- versus Omicron-predominant wave (subhazard ratio [sHR], 0.94; 95% confidence interval [CI], 0.74-1.19), but patients supported with VV-ECMO during the Omicron-predominant wave had a significantly lower adjusted risk of hospital mortality at 90 days (subhazard ratio, 0.71; 95% CI, 0.51-0.99). Patients receiving VV-ECMO during the Omicron-predominant wave had a similar unadjusted risk of hospital mortality at 90 days, but a significantly lower adjusted risk of hospital mortality at 90 days than those receiving VV-ECMO during the Delta-predominant wave., Competing Interests: Disclosure: D.B. receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. D.A. and C.A. write for UpToDate. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Adolescent intermittent ethanol (AIE) exposure, which models heavy binge ethanol intake in adolescence, leads to a variety of deficits that persist into adulthood-including suppression of the cholinergic neuron phenotype within the basal forebrain. This is accompanied by a reduction in acetylcholine (ACh) tone in the medial prefrontal cortex (mPFC). Voluntary wheel running exercise (VEx) has been shown to rescue AIE-induced suppression of the cholinergic phenotype. Therefore, the goal of the current study is to determine if VEx will also rescue ACh efflux in the mPFC during spontaneous alternation, attention set shifting performance, and epigenetic silencing of the cholinergic phenotype following AIE. Male and female rats were subjected to 16 intragastric gavages of 20% ethanol or tap water on a two-day on/two-day off schedule from postnatal day (PD) 25-54, before being assigned to either VEx or stationary control groups. In Experiment 1, rats were tested on a four-arm spontaneous alternation maze with concurrent in vivo microdialysis for ACh in the mPFC. An operant attention set-shifting task was used to measure changes in cognitive and behavioral flexibility. In Experiment 2, a ChIP analysis of choline acetyltransferase (ChAT) genes was performed on basal forebrain tissue. It was found that VEx increased ACh efflux in the mPFC in both AIE and control male and female rats, as well as rescued the AIE-induced epigenetic methylation changes selectively at the Chat promoter CpG island across sexes. Overall, these data support the restorative effects of exercise on damage to the cholinergic projections to the mPFC and demonstrate the plasticity of cholinergic system for recovery after alcohol induced brain damage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fecik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

SARS-CoV-2 vaccine-acquired immunity provides robust cross-variant recognition, while infection-acquired immunity can be heterogenous, with disease severity often modulating post-recovery responses. We assessed antibody waning dynamics between infection- and vaccination-acquired immunity across variants of concern (VOC). mRNA vaccination induced potent, cross-VOC Spike recognition and functional responses, but waned more rapidly for Omicron Spike. Hospitalized individuals developed more durable functional responses with lower peaks compared to mRNA vaccination, while outpatients exhibited slower decay than inactivated vaccine recipients. Humoral decay for the receptor binding domain tracked with neutralizing antibody titers, while S2-directed responses tracked with antibody-dependent myeloid cellular phagocytosis. Boosting the recovered patients with mRNA or inactivated vaccines expanded humoral breadth, durability, and restored functional responses, eliminating the severity- and platform-associated decay differences. Therefore, post-recovery hybrid immunization compensates for this distinction and broadens humoral breadth, highlighting the value of boosting immunity in previously infected individuals., One Sentence Summary: Infection- and vaccine-acquired immunity to COVID-19 exhibit different functional antibody profiles, each characterized by distinct kinetics of waning over time.

Objective: Acute intranasal (IN) instillation of lupus-prone NZBWF1 mice with crystalline silica (cSiO 2 ) triggers robust lung inflammation that drives autoimmunity. Prior studies in other preclinical models show that soluble epoxide hydrolase (sEH) inhibition upregulates pro-resolving lipid metabolites that are protective against pulmonary inflammation. Herein, we assessed in NZBWF1 mice how acute IN cSiO 2 exposure with or without the selective sEH inhibitor TPPU influences lipidomic, transcriptomic, proteomic, and histopathological biomarkers of inflammation, fibrosis, and autoimmunity., Methods: Female 6-week-old NZBWF1 mice were fed control or TPPU-supplemented diets for 2 weeks then IN instilled with 2.5 mg cSiO 2 or saline vehicle. Cohorts were terminated at 7 or 28 days post-cSiO 2 instillation (PI) and lungs analyzed for prostaglandins, cytokines/chemokines, gene expression, differential cell counts, histopathology, and autoantibodies., Results: cSiO 2 -treatment induced prostaglandins, cytokines/chemokine, proinflammatory gene expression, CD206 + monocytes, Ly6B.2 + neutrophils, CD3 + T cells, CD45R + B cells, centriacinar inflammation, collagen deposition, ectopic lymphoid structure neogenesis, and autoantibodies. While TPPU effectively inhibited sEH as reflected by skewed lipidomic profile in lung and decreased cSiO 2 -induced monocytes, neutrophils, and lymphocytes in lung lavage fluid, it did not significantly impact other biomarkers., Discussion: cSiO 2 evoked robust pulmonary inflammation and fibrosis in NZBWF1 mice that was evident at 7 days PI and progressed to ELS development and autoimmunity by 28 days PI. sEH inhibition by TPPU modestly suppressed cSiO 2 -induced cellularity changes and pulmonary fibrosis. However, TPPU did not affect ELS formation or autoantibody responses, suggesting sEH minimally impacts cSiO 2 -triggered lung inflammation, fibrosis, and early autoimmunity in our model.

Animals are motivated to seek information that does not influence reward outcomes, suggesting that information has intrinsic value. We have developed an odor-based information seeking task that reveals that mice choose to receive information even though it does not alter the reward outcome. Moreover, mice are willing to pay for information by sacrificing water reward, suggesting that information is of intrinsic value to a mouse. We used a microendoscope to reveal neural activity in orbitofrontal cortex (OFC) while mice learned the information seeking task. We observed the emergence of distinct populations of neurons responsive to odors predictive of information and odors predictive of water reward. A latent variable model recapitulated these different representations in the low-dimensional dynamics of OFC neuronal population activity. These data suggest that mice have evolved separate pathways to represent the intrinsic value of information and the extrinsic value of water reward. Thus, the desire to acquire knowledge is observed in mice, and the value of this information is represented in the OFC. The mouse now provides a facile experimental system to study the representation of the value of information, a higher cognitive variable., Competing Interests: Competing interests: Authors declare that they have no competing interests.

Background: Plitidepsin has shown potent preclinical activity against severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (COVID-19). NEPTUNO, a phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients., Methods: Included patients had documented severe acute respiratory syndrome coronavirus 2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety., Results: After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio, 1.37; 95% confidence interval, .96-1.96; P = .08 for plitidepsin 1.5 mg vs control; hazard ratio, 1.06; 95% confidence interval, .73-1.53; P = .78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated., Conclusions: Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted.Results from this phase III trial suggest that plitidepsin, a first-in-class antiviral, may have a positive benefit-risk ratio in the management of hospitalized patients requiring oxygen therapy for moderate COVID-19., Competing Interests: Potential conflicts of interest. V. E. has received economic support for educational talks and advisory boards from Gilead Sciences and PharmaMar SA. M. M-M. has received grants and fees for scientific advice not related with this work; received in the past 36 months from Boehringer Ing, Roche, Ferrer, Chiesi. P. V. has received provision of study materials, travel support travel from PharmaMar SA, and payments from PharmaMar SA and GlaxoSmithKline (GSK). P. G-V. received speaker fees from FLS Science, PharmaMar SA (Madrid, Spain), Pfizer (Spain), and GSK (Spain); consulting fees from Angelini Pharma and PharmaMar SA; served as an advisory board member for Berlin Cures GmbH and PharmaMar SA; and received meeting grants from GSK and PharmaMar SA. A. L. has received occasional training fees from Gilead, is a member of a Data Monitoring Committee for a randomized controlled trial for Biophytis Biopharma. R. P. has received grants or contracts from MSD, ViiV Healthcare; consulting fees Pfizer, Gilead, AstraZeneca, PharmaMar SA, GSK, Atea. G. P. has received fees, as member advisory panels and consultancy, from Pfizer, MSD, Menarini, and Gilead. M. M. has received fees from Boehringer as scientific advisor and payments for lectures and educational events from GSK. J. F. has received grants and payments from Gilead, Pfizer, Shionogy, Astellas, and MSD, as well as travel support. P. R. has received fees and travel support from Gilead, Merck, VIV, and Gesida. D. L-M., E-M. S-L, F. M., J. G., and N. T. are a full-time employees of PharmaMar. J. J. holds stocks of Pangaea Oncology, has a nonremunerated role in the Scientific Advisory Board, and holds stocks of Promontory Therapeutics; is a full-time employee and shareholder of PharmaMar, S.A. (Madrid, Spain), and a co-inventor of 2 patents for Plitidepsin (WO99-42125). J. A. L.-M. is a full-time employee and shareholder of PharmaMar, S.A (Madrid, Spain), and a co-inventor of a patent for plitidepsin (WO2008135793A1). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development., Competing Interests: Declaration of Interests Declarations of interest: None

The separation and purification of xylene isomers is critical to the production of polyethylene terephthalate (PET). These separations are complex to operate and demand tremendous amounts of energy and thus are an opportunity for reducing industrial energy consumption. Membranes provide a low-energy footprint technology with simpler operation, and recently, membrane materials have been developed that are capable of separating xylene isomers. While these materials have demonstrated the ability to separate xylenes, they have yet to be commercially deployed. This work conducts a techno-economic analysis (TEA) to provide insight on the commercial attractiveness of a p -xylene selective carbon molecular sieve (CMS) membrane from both a cost and energy standpoint. This TEA was conducted through the pairing of a Maxwell-Stefan transport framework for rigid microporous materials with process modeling. Single-stage organic solvent reverse osmosis (OSRO) and pervaporation processes were used to evaluate the effects of recovery, selectivity, and diffusivity on the energy intensity and cost of the xylene separation. The final analysis used two systems, a single pervaporation stage followed by two OSRO stages, which was compared against a three-stage OSRO cascade. These were benchmarked against the commercial Parex process. We estimate that the membrane processes have the potential to enable impressive cost savings compared to the Parex process. While both systems outperformed the Parex process in terms of cost, the pervaporation/OSRO hybrid process was able to achieve the lowest cost of all due to its reduced membrane surface area compared to standalone OSRO. These findings demonstrate the potential of membrane systems in the field of difficult small molecule solvent separations., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Climate change is reducing winter ice cover on lakes; yet, the full societal and environmental consequences of this ice loss are poorly understood. The socioeconomic implications of declining ice include diminished access to ice-based cultural activities, safety concerns in traversing ice, changes in fisheries, increases in shoreline erosion, and declines in water storage. Longer ice-free seasons allow more time and capacity for water to warm, threatening water quality and biodiversity. Food webs likely will reorganize, with constrained availability of ice-associated and cold-water niches, and ice loss will affect the nature, magnitude, and timing of greenhouse gas emissions. Examining these rapidly emerging changes will generate more-complete models of lake dynamics, and transdisciplinary collaborations will facilitate translation to effective management and sustainability.

Introduction: While frailty has gained attention for its utility in risk stratification, no studies have directly compared them to existing risk calculators. The objective of this study was to compare the risk stratification of the American College of Surgeons Surgical Risk Calculator (ACS-SRC), the Revised Risk Analysis Index (RAI-rev), and the Modified Frailty Index (5-mFI). The primary outcomes were 30-day postoperative morbidity, 30-day postoperative mortality, unplanned readmission, unplanned reoperation, and discharge disposition other than home., Methods: Patients undergoing anatomic lung resection for primary, nonsmall cell lung cancer were identified within the ACS National Quality Improvement Program (ACS NSQIP) database. Tools were compared for discrimination in the primary outcomes., Results: 9663 patients undergoing anatomic lung resection for cancer between 2012 and 2014 were included. The cohort was 53.1% female. Median age at diagnosis was 67 (IQR 59-74) years. Perioperative morbidity and mortality rates were 10.9% (n = 1048) and 1.6% (n = 158). Rates of 30-day postoperative unplanned readmission and reoperation were 7.5% (n = 725) and 4.8% (n = 468). The ACS-SRC had the highest discrimination for all measured outcomes, as measured by the area under the receiver operating curve (AUC) and corresponding confidence interval (95% CI). This included perioperative mortality (AUC 0.74, 95% CI 0.71-0.78), compared to RAI-rev (AUC 0.66, 95% CI 0.62-0.69) and 5-mFI (AUC 0.61, 95% CI 0.57-0.65; p < 0.001). The RAI-rev and 5-mFI had similar discrimination for all measured outcomes., Conclusion: ACS-SRC was the perioperative risk stratification tool with the highest predictive discrimination for adverse, 30-day, postoperative events for patients with cancer treated with anatomic lung resection., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

The growing need for collaborative healthcare teams to meet complex health challenges has led to physical therapists (PTs) being embedded in adult primary care settings for many years now. However, this model of care has not been found in pediatrics. This qualitative study sought to gain insights from pediatricians on the potential of embedding pediatric PTs in primary care. Participants were nine pediatricians practicing in both urban and rural, hospital-based and private settings. Semi-structured interviews were recorded, transcribed, and analyzed via thematic analysis per published methods, assuring trustworthiness. Three overarching themes emerged: pediatricians' priorities aligned with the Quadruple Aim of Healthcare, embedded PTs could fill multiple roles in pediatrics, and they could see a wide variety of patients, highlighting real potential benefits in primary care. Participants endorsed in-office focused treatments, screening to determine optimal care pathways, and ongoing patient follow-up as potential PT roles in this setting. Providers thought that PTs could help manage care for musculoskeletal complaints, high-risk infants, medically complex children, autism, and obesity. An advanced-trained PT having attributes of confidence, adaptability, and open-mindedness was desired. All participants endorsed pediatric primary care PTs as having potentially high value in their practice. This is the first known study on the potential of embedding a PT in the pediatric primary care setting, offering valuable insights from pediatricians to be leveraged in implementation planning.

Benzalkonium chlorides (BACs) are commonly used disinfectants in a variety of consumer and food-processing settings, and the COVID-19 pandemic has led to increased usage of BACs. The prevalence of BACs raises the concern that BAC exposure could disrupt the gastrointestinal microbiota, thus interfering with the beneficial functions of the microbes. We hypothesize that BAC exposure can alter the gut microbiome diversity and composition, which will disrupt bile acid homeostasis along the gut-liver axis. In this study, male and female mice were exposed orally to d7-C12- and d7-C16-BACs at 120 µg/g/day for one week. UPLC-MS/MS analysis of liver, blood, and fecal samples of BAC-treated mice demonstrated the absorption and metabolism of BACs. Both parent BACs and their metabolites were detected in all exposed samples. Additionally, 16S rRNA sequencing was carried out on the bacterial DNA isolated from the cecum intestinal content. For female mice, and to a lesser extent in males, we found that treatment with either d7-C12- or d7-C16-BAC led to decreased alpha diversity and differential composition of gut bacteria with notably decreased actinobacteria phylum. Lastly, through a targeted bile acid quantitation analysis, we observed decreases in secondary bile acids in BAC-treated mice, which was more pronounced in the female mice. This finding is supported by decreases in bacteria known to metabolize primary bile acids into secondary bile acids, such as the families of Ruminococcaceae and Lachnospiraceae. Together, these data signify the potential impact of BACs on human health through disturbance of the gut microbiome and gut-liver interactions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations ( BAZ2B and DDIAS ). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP . Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research., Competing Interests: SD, RC, AL, JL, Md, IQ, RG, VN, MP, JT, JN, JA, CA, SA, VA, BA, NA, ÁA, EA, CA, MA, MA, RB, MB, MB, JB, MB, LB, MB, RB, MB, EC, CC, LC, JC, RC, MC, JC, MC, MD, AD, Vd, Ad, ED, RE, MF, MF, UF, AF, TF, MG, BG, JG, BÁ, FB, AG, JG, JG, MH, AH, MJ, ML, AB, RL, EM, CM, VM, OM, IM, MM, AM, JM, EM, PM, VC, SO, EO, MP, EP, NS, PP, PP, MP, TP, MP, GP, EP, GP, AP, SL, SR, MF, ER, FR, JR, FR, JR, PR, JS, JS, ET, AT, JT, AT, LT, MU, JV, ZY, RZ, Id, AR, PS, LR, EG, CA, EP, JR, AR, CF, PL, ÁC No competing interests declared, (© 2024, Diz-de Almeida, Cruz et al.)

Background: The goal of treatment of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is suppression of both viruses; yet incomplete HBV suppression on tenofovir (TFV) disoproxil fumarate (TDF)-based antiretroviral therapy (ART) is common. This study investigated TFV resistance-associated mutations (RAMs) in individuals with HBV/HIV coinfection with viremia on TDF/lamivudine (3TC)-containing ART., Methods: Samples from individuals with HBV DNA levels ≥20 IU/mL in a cross-sectional study of 138 persons with HBV/HIV coinfection in Ghana were analyzed in the present study. HBV was sequenced for RAM analysis. TFV-diphosphate (TFV-DP) concentration in peripheral blood mononuclear cells (PBMCs) was used to assess ART adherence level., Results: Nine of 138 participants (6.5 %) had detectable HBV DNA levels ≥20 IU/mL while on ART. Seven of the nine participants had TFV-DP concentrations commensurate with 7 doses per week, and six had suppressed HIV RNA. Phylogenetic analysis revealed that eight sequences were HBV genotype E, with one genotype E/A recombinant. Ten previously-reported TFV RAMs were present in the study samples; eight were wild-type for HBV genotype E. The non-genotype-E-wild-type point mutations M267L and K333Q were found in two and one patients, respectively. No 3TC RAMs were found., Conclusion: HBV viremia despite high adherence to TDF/3TC-based ART may be associated with the presence of TFV RAMs. These findings highlight the need for enhanced resistance monitoring and further research to examine the clinical significance of reported TFV RAMs. Individuals with HBV/HIV coinfection and TFV resistance on TDF-based ART may need alternative treatment strategies., Competing Interests: Declaration of competing interest The authors report no conflicts of interest related to this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Background: The Infectious Diseases Society of America (IDSA) developed the Core Antimicrobial Stewardship (AS) Curriculum to meet the increasing demand for infectious diseases (ID) providers with AS expertise. Notable diversity in implementation approaches has been observed among ID fellowship programs using the curriculum. We sought to describe individual approaches and develop a curriculum implementation roadmap., Methods: We surveyed ID fellowship programs that had previously implemented the IDSA Core AS curriculum. The survey included questions regarding program characteristics, curriculum participants and presentation format, resources and barriers, and implementation strategies. Commonly reported program features were summarized in the context of the self-reported implementation strategies. Implementation guides were developed based on the most common characteristics observed., Results: Of 159 programs that had purchased the curriculum, 37 responded, and 34 (21%) were included in the analysis. The curriculum was primarily taught by AS physicians (85%) and AS pharmacists (47%). The most common conference structure was a longitudinal conference series (32%), and eLearning was the most common presentation format. Limited AS faculty time (76%) and limited first-year fellow availability (62%) were frequently reported as barriers, and dedicated AS curricular time was a resource available to most programs (67%); implementation guides were created for these 3 program features., Conclusions: Programs reported a variety of implementation barriers and resources, with several common themes emerging, allowing for the development of tailored curriculum planners for 3 commonly observed program characteristics. This work will equip fellowship programs with curriculum implementation strategies and guide future enhancements of the IDSA Core and Advanced AS curricula., Competing Interests: Potential conflicts of interest. A. Y. K. has received research funding from Paratek Pharmaceuticals and American College of Clinical Pharmacy. G. F. has received funding from Critical Innovations, LLC, and grant funding from Melinta Therapeutics. K. C. has received research grants from the National Institutes of Health, Biomedical Advanced Research and Development Authority, and Merck and panel discussion honorarium from Ferring. E. J. S. has received research funding from Merck and bioMérieux. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Hepatitis C virus (HCV) microelimination aims to detect and treat hidden infections, especially in at-risk groups, like people experiencing homelessness (PEH) with alcohol or drug use disorders. Point-of-care HCV RNA testing and peer support workers are crucial for identifying and preventing HCV infection among marginalized populations, contributing to overall elimination goals., Objective: To assess risk factors, prevalence, and trends of active HCV infection among PEH in Madrid, Spain (2019-2023)., Design, Setting, and Participants: This cross-sectional study was conducted between 2019 and 2023 in PEH, defined as people who lacked a fixed, regular, and adequate night residence, screened on the street or in homeless shelters via mobile unit using rapid HCV antibody testing, followed by HCV-RNA testing in Madrid, Spain. Data were analyzed from January to June 2024., Main Outcomes and Measures: Active HCV infection among PEH was the main outcome. Risk factors analyzed included being born outside of Spain, alcohol misuse, lacking financial income, benzodiazepine use, injection drug use (IDU; including nonactive IDU and active IDU within the last year), opioid substitution therapy participation, and sexual behavior patterns. Data were analyzed using logistic regression. P values were adjusted for multiple testing using the false discovery rate (q-values)., Results: A total of 4741 individuals were screened for HCV infection, of whom 2709 (mean [SD] age, 42.2 [12.7]; 1953 [72.2%] men) were PEH and included in analysis. A total of 363 PEH (13.4%) had test results positive for HCV antibodies, of whom 172 (47.4%) had test results positive for HCV-RNA, and 148 of these (91.9%) started HCV treatment. Overall, active HCV infection prevalence was 6.3%, and the main risk factors associated with active HCV infection included IDU, encompassing both nonactive IDU (adjusted odds ratio [aOR], 10.9; 95% CI, 6.1-19.4; q < .001) and active IDU in the last year (aOR, 27.0; 95% CI, 15.2-48.0; q < .001); a lack of financial income (aOR, 1.8; 95% CI, 1.1-2.9; q = .03); and alcohol misuse (aOR, 1.8; 95% CI, 1.3-2.6; q = .008). There was a significant decrease between 2019 and 2023 in active HCV infection prevalence across the entire population, from 7.2% to 3.4% (P = .04)., Conclusions and Relevance: In this cross-sectional study of PEH in Madrid, IDU, lack of income, and alcohol misuse were primary risk factors associated with HCV infection. The significant decline in HCV rates observed across all risk groups during the study period suggests preventive policies were effective in reducing HCV prevalence among the homeless population.

Dried blood spot (DBS) sampling is increasingly used for hepatitis C virus (HCV) screening. HCVcAg testing offers a faster and more streamlined approach to diagnosing HCV infection. We conducted a systematic review and meta-analysis to assess the diagnostic performance of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection using DBS samples. Eight studies (n = 1229) were selected among all published studies available up to October 4, 2024, in different databases with a search strategy registered (PROSPERO: CRD42022363975). The gold standard method was the HCV PCR test. Data were analyzed using the MIDAS module in STATA with a random effects model. Combined diagnostic accuracy measures were as follows: sensitivity 85%, specificity 100%, positive likelihood ratio (PLR) 233.1, negative likelihood ratio (NLR) 0.15, and summary receiver operating characteristic (SROC) 0.99. Likelihood ratios and Fagan's nomogram suggested that the HCVcAg assay with DBS samples can confirm or rule out active HCV infection with over 92% accuracy in high-prevalence settings (≥5%). However, in low-prevalence settings (≤1%), a confirmatory test must be required for positive results. The ability of the test to identify people without HCV infection was high regardless of HCV prevalence, with an error rate of less than 3%. This meta-analysis is subject to limitations, particularly due to the number of included studies and significant heterogeneity among them. HCV screening using the Abbott ARCHITECT HCV Ag assay with DBS samples showed excellent diagnostic performance, but its external validity may be limited when HCV prevalence is low (≤1%)., (© 2024 Wiley Periodicals LLC.)

Extracorporeal membrane oxygenation (ECMO) is a high-risk and low-volume life support with increasing clinical study. However, heterogenous outcome definitions impede data assimilation into evidence to guide practice. The Academic Research Consortium (ARC), an international collaborative forum committed to facilitating the creation of stakeholder-driven consensus nomenclature and outcomes for clinical trials of medical devices, supported the ECMO Core Elements Needed for Trials Regulation And quality of Life (ECMO-CENTRAL) ARC. The ECMO-CENTRAL ARC was assembled to develop definitions of paediatric ECMO adverse events for use in clinical trials and regulatory device evaluation. An initial candidate list of ECMO adverse events derived from the mechanical circulatory support ARC was supplemented with a review of ECMO-relevant adverse event definitions collated from literature published between Jan 1, 1988, and Feb 20, 2023. Distinct teams of international topic experts drafted separate adverse event definitions that were harmonised to existing literature when appropriate. Draft definitions were revised for paediatric ECMO relevance with input from patients, families, and an international expert panel of trialists, clinicians, statisticians, biomedical engineers, device developers, and regulatory agencies. ECMO-CENTRAL ARC was revised and disseminated across research societies and professional organisations. Up to three rounds of internet-based anonymous surveys were planned as a modified Delphi process. The expert panel defined 13 adverse event definitions: neurological, bleeding, device malfunction, acute kidney injury, haemolysis, infection, vascular access-associated injury, non-CNS thrombosis, hepatic dysfunction, right heart failure, left ventricular overload, lactic acidaemia, and hypoxaemia. Definitional structure varied. Among 165 expert panel members, 114 were eligible to vote and 111 voted. Consensus was achieved for all proposed definitions. Agreement ranged from 82% to 95%. ECMO-CENTRAL ARC paired rigorous development with methodical stakeholder involvement and dissemination to define paediatric ECMO adverse events. These definitions will facilitate new research and the assimilation of data across clinical trials and ECMO device evaluation in children., Competing Interests: Declaration of interests PMAA reports institution funding from the US Department of Defense (PRMRP clinical trial award #W81XWH2210301), National Institutes of Health (NIH R13HD104432), and the US Food and Drug Administration (FDA Grant Number U01FD004979/U01FD005978); and is the Treasurer for Extracorporeal Life Support Organization (ELSO). MDN is a member of the advisory board for Eurosets and a member of the European ELSO Chapter Steering Committee. MVA, NB, and LV are members of the European ELSO Chapter Steering Committee. DB received research support and consulting fees from LivaNova; has been on medical advisory boards for Xenios, Medtronic, Inspira, and Cellenkos; is the President-Elect of ELSO and the Chair of the Executive Committee of the International ECMO Network (ECMONet); and writes for UpToDate. RG-G is a member of the Latin American ELSO Chapter Steering Committee. PMK is a member or the Southwest Asia and Africa ELSO Chapter Steering Committee. GM is President of ELSO. MLP is the Past President of ELSO. AR-P is a consultant for Terumo CVS; and his institution receives funding from the NIH (R01 HL141509 and R01 HL155100). AL is a consultant for Bayer, Abbott, Abiomed, Berlin Heart, and Syncardia; is the primary investigator for the Berlin ACTIVE driver trial; and is an Executive of the ACTION Network. RPB reports a grant from the NIH (R01 HL153519) and is a member of the ELSO Board of Directors and Co-Chair of PediECMO., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Aims: Current data are insufficient for the leading resuscitation societies to advise on the use of extracorporeal cardiopulmonary resuscitation (ECPR) for pediatric out-of-hospital cardiac arrest (OHCA). The aim of this study was to explore the current utilization of ECPR for pediatric OHCA and characterize the patient demographics, arrest features, and metabolic parameters associated with survival., Methods: Retrospective review of the Extracorporeal Life Support Organization Registry database from January 2020 to May 2023, including children 28 days to 18 years old who received ECPR for OHCA. The primary outcome was survival to hospital discharge., Results: Eighty patients met inclusion criteria. Median age was 8.8 years [2.0-15.8] and 53.8% of patients were male. OHCA was witnessed for 65.0% of patients and 46.3% received bystander cardiopulmonary resuscitation (CPR). Initial rhythm was shockable in 26.3% of patients and total CPR duration was 78 min [52-106]. Signs of life were noted for 31.3% of patients and a cardiac etiology precipitating event was present in 45.0%. Survival to discharge was 29.9%. Initial shockable rhythm was associated with increased odds of survival (unadjusted OR 4.7 [1.5-14.5]; p = 0.006), as were signs of life prior to ECMO (unadjusted OR 7.8 [2.6-23.4]; p < 0.001). Lactate levels early on-ECMO (unadjusted OR 0.89 [0.79-0.99]; p = 0.02) and at 24 h on-ECMO (unadjusted OR 0.62 [0.42-0.91]; p < 0.001) were associated with decreased odds of survival., Conclusions: These preliminary data suggest that while overall survival is poor, a carefully selected pediatric OHCA patient may benefit from ECPR. Further studies are needed to understand long-term neurologic outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “Ryan P. Barbaro reports a relationship with Extracorporeal Life Support Organization that includes: board membership. Peta M.A. Alexander reports a relationship with Extracorporeal Life Support Organization that includes: board membership. Ryan P. Barbaro reports a relationship with Pedi-ECMO that includes: board membership. Ryan P. Barbaro reports a relationship with National Institutes of Health that includes: funding grants. Peta M.A. Alexander reports a relationship with US Department of Defense that includes: funding grants. Peta M.A. Alexander reports a relationship with National Institutes of Health that includes: funding grants. Peta M.A. Alexander reports a relationship with US Food and Drug Administration that includes: funding grants. If there are other authors, they 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Cocaine use (CU) is prevalent in people with HIV (PWH). Both conditions are linked to changes in cognitive functioning and neural network topology. The current study utilizes graph theory to investigate functional connectomics associated with HIV and CU, focusing on disruption of densely connected nodes called hubs., Methods: Resting state functional magnetic resonance imaging (fMRI) from 206 adults (ages 22-55 years) were analyzed. A HIV x CU factorial design was implemented with participants in four groups: HIV+CU (n= 41), HIV only (n= 88), CU only (n= 36), and controls (n= 41). Functional connectomes were constructed, and thresholded graph metrics were calculated. Network centrality metrics - betweenness centrality (BC), participation coefficient (PC), and within module degree (WD) - were quantified into hub disruption indices (HDI). For each index, a 2×2 ANCOVA was performed controlling for education., Results: Participants were 68 % male and 74 % African-American with a mean age of 44.4 years. HIV and CU were associated with hub disruption in all three indices. Interactions were significant for HDI-PC and HDI-WD, such that HIV disease was associated with greater hub disruption among participants without CU, but not among participants with CU. Overall, lower global cognitive functioning was associated with greater hub disruption on all three indices., Conclusions: Widespread hub disruption was evident in HIV disease and CU, highlighting topological reorganization in both diseases with neurocognitive effects. Hub-related measures inform functional connectivity disruptions in HIV disease and CU, particularly with respect to changes in network topology throughout the connectome., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Surgical care in the operating room (OR) contributes one-third of the greenhouse gas (GHG) emissions in healthcare. The European Association of Endoscopic Surgery (EAES) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) initiated a joint Task Force to promote sustainability within minimally invasive gastrointestinal surgery., Methods: A scoping review was conducted by searching MEDLINE via Ovid, Embase via Elsevier, Cochrane Central Register of Controlled Trials, and Scopus on August 25th, 2023 to identify articles reporting on the impact of gastrointestinal surgical care on the environment. The objectives were to establish the terminology, outcome measures, and scope associated with sustainable surgical practice. Quantitative data were summarized using descriptive statistics., Results: We screened 22,439 articles to identify 85 articles relevant to anesthesia, general surgical practice, and gastrointestinal surgery. There were 58/85 (68.2%) cohort studies and 12/85 (14.1%) Life Cycle Assessment (LCA) studies. The most commonly measured outcomes were kilograms of carbon dioxide equivalents (kg CO 2 eq), cost of resource consumption in US dollars or euros, surgical waste in kg, water consumption in liters, and energy consumption in kilowatt-hours. Surgical waste production and the use of anesthetic gases were among the largest contributors to the climate impact of surgical practice. Educational initiatives to educate surgical staff on the climate impact of surgery, recycling programs, and strategies to restrict the use of noxious anesthetic gases had the highest impact in reducing the carbon footprint of surgical care. Establishing green teams with multidisciplinary champions is an effective strategy to initiate a sustainability program in gastrointestinal surgery., Conclusion: This review establishes standard terminology and outcome measures used to define the environmental footprint of surgical practices. Impactful initiatives to achieve sustainability in surgical practice will require education and multidisciplinary collaborations among key stakeholders including surgeons, researchers, operating room staff, hospital managers, industry partners, and policymakers., (© 2024. The Author(s).)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: We analyzed epidemiological, clinical characteristics, and the response to treatment in people living with HIV (PLHIV) who recently acquired hepatitis C (RAHC) in a multicentre study in Madrid (Spain)., Methods: Multicenter, ambispective, observational study of RAHC in men who have sex with men (MSM) infected with HIV. Clinical, epidemiological, and RAHC evolution were recorded prospectively in 2019 and 2020 and retrospectively in 2017 and 2018. In patients who received HCV treatment, sustained virological response (SVR) was provided 12 weeks after the end of treatment in an intention to treat analysis (ITT): all treated patients were included; and in analysis per-protocol (PP): missing patients were excluded., Results: Overall, 133 patients were included. Median (IQR) age was 40 (34.3-46.1) years, 90.9% had at least one previous sexual transmission disease (STD), and 33.6% had previously hepatitis C. More than half of the prospective sample included patients using chemsex related drugs (57.3%), 45.7% of them intravenously. The most prevalent genotype was G1a (66.2%), followed by G4 (11.3%). Ten of 90 patients evaluated for spontaneous cure (11%) cured the infection spontaneously, and 119 had treatment after a median time of 1.8 (0.7-4.6) months: sustained virological response (SVR) was achieved in 90.7% in the ITT and 94.7% in the PP analysis, with no differences regarding the direct-acting antiviral agents (DAA) combination used., Conclusions: MSM infected by HIV with a RAHC were exposed to high-risk sexual behavior. Spontaneous cure rate was low, while SVR after treatment was achieved by more than 90%., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Surgical care significantly contributes to healthcare-associated greenhouse gas emissions (GHG). Surgeon attitudes about mitigation of the impact of surgical practice on environmental sustainability remains poorly understood. To better understand surgeon perspectives globally, the Society of American Gastrointestinal and Endoscopic Surgeons and the European Association for Endoscopic Surgery established a joint Sustainability in Surgical Practice (SSP) Task Force and distributed a survey on sustainability., Methods: Our survey asked about (1) surgeon attitudes toward sustainability, (2) ability to estimate the carbon footprint of surgical procedures and supplies, (3) concerns about the negative impacts of sustainable interventions, (4) willingness to change specific practices, and (5) preferred educational topics and modalities. Questions were primarily written in Likert-scale format. A clustering analysis was performed to determine whether survey respondents could be grouped into distinct subsets to inform future outreach and education efforts., Results: We received 1024 responses, predominantly from North America and Europe. The study revealed that while 63% of respondents were motivated to enhance the sustainability of their practice, less than 10% could accurately estimate the carbon footprint of surgical activities. Most were not concerned that sustainability efforts would negatively impact their practice and showed readiness to adopt proposed sustainable practices. Online webinars and modules were the preferred educational methods. A clustering analysis identified a group particularly concerned yet willing to adopt sustainable changes., Conclusion: Surgeons believe that operating room waste is a critical issue and are willing to change practice to improve it. However, there exists a gap in understanding the environmental impact of surgical procedures and supplies, and a sizable minority have some degree of concern about potential adverse consequences of implementing sustainable policies. This study uniquely provides an international, multidisciplinary snapshot of surgeons' attitudes, knowledge, concerns, willingness, and preferred educational modalities related to mitigating the environmental impact of surgical practice., (© 2024. The Author(s).)

Hyaluronan (HA) is a glycosaminoglycan that forms a gel-like barrier in the subcutaneous (SC) space, limiting bulk fluid flow and the dispersion of SC-administered therapeutics. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the rapid delivery of co-administered therapeutics by depolymerizing HA in the SC space. Administration of rHuPH20 can induce the formation of anti-rHuPH20 antibodies, or anti-drug antibodies (ADAs), with the potential to bind endogenous PH20 hyaluronidase in the adult testes and epididymis. Using a variety of relevant animal models and multiple dose regimens of rHuPH20 across the full spectrum of animal development, we demonstrated that rHuPH20 administration resulted in the formation of ADAs. Although these ADAs can bind both the recombinant rHuPH20 enzyme and recombinant versions of animal model-specific hyaluronidases, they had no impact on fertility parameters (as measured by sperm concentration and motility, litter size, and litter viability) or fetal development. We present the result of our nonclinical studies in order of the developmental lifecycle, beginning with adults. Toxicology studies that extend beyond the standard package are also presented. These studies demonstrate the favorable safety profile of rHuPH20 and ADAs in nonclinical models. Additionally, we identified substantial safety margins for clinically relevant doses of rHuPH20., Competing Interests: Declaration of competing interest Authors are current or former employees and shareholders of Halozyme Therapeutics, Inc. Halozyme, Inc. is not the HALO stock., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: We performed a randomized controlled trial assessing patient-reported outcome measures following trapeziectomy with ligament reconstruction and tendon interposition (LRTI) or suture tape suspensionplasty (STS) for treatment of thumb carpometacarpal joint osteoarthritis., Methods: Patients undergoing surgery for thumb carpometacarpal joint osteoarthritis were prospectively randomized to LRTI or STS. Outcome measures were collected at 2 weeks, 4 weeks, 3 months, and 1 year and included visual analog scale pain, Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity, return to work/activity, range of motion, grip/pinch strength, and complications., Results: Thirty-one patients (32 thumbs) were randomized from 51 patients offered participation over two years. One-year follow-up was 97%. Both groups had a decrease in visual analog scale pain scores at all postoperative time points. The trajectory of postoperative Patient-Reported Outcomes Measurement Information System Upper Extremity scores was similar, and both groups achieved the meaningful clinically important difference for improvement in PROMIS Upper Extremity by three months. Grip strength was substantially increased in both groups at one year. Return to work/activity and surgical complications favored the LRTI group., Conclusions: Our study did not suggest any clinically relevant differences in the postoperative patient-reported outcome measures or objective clinical measurements between LRTI and STS, although LRTI patients had a faster return to work/activity and lower complication rates., Type of Study/level of Evidence: Therapeutic IIB., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: In mechanistic and preliminary human studies, prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with oxidative stress, a potential contributor to maternal liver disease. Bilirubin is an endogenous antioxidant abundant in the liver that may serve as a physiological modulator of oxidative stress in pregnant people. Hence, our objective was to estimate the association between repeated measures of PFAS and bilirubin during pregnancy., Methods: The study population included 332 participants in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Serum samples were collected up to two times (early pregnancy: 6-18 gestational weeks; late pregnancy: 21-36 gestational weeks) for the measurement of perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and total bilirubin. We analyzed single PFAS with linear mixed effect regression and a mixture of the four PFAS with quantile g-computation. Models were repeated with a multiplicative interaction term to explore effect modification by study visit., Results: Overall, PFHxS was positively associated with bilirubin (β = 0.08, 95 % CI = 0.01, 0.15). We also found during late pregnancy, there was a positive association of PFHxS and the PFAS mixture with bilirubin (β = 0.12, 95 % CI = 0.02, 0.22; ψ = 0.19, 95 % CI = 0.03, 0.34, respectively). Finally, study visit modified the PFOA-bilirubin association (interaction p-value = 0.09), which was greater during early pregnancy (β = 0.08, 95 % CI = 0.01, 0.15)., Conclusion: In a prospective cohort of pregnant African Americans, an increase in PFOA, PFHxS, and the PFAS mixture was associated with an increase in bilirubin. Our results suggest that, depending on pregnancy stage, prenatal PFAS exposure disrupts the maternal liver antioxidant capacity., 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 © 2024. Published by Elsevier Inc.)

Targeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here, it is reported that the development of small molecule degraders of the envelope (E) protein of dengue virus. Two classes of bivalent E-degraders are developed by linking two previously reported E-binding small molecules, GNF-2, and CVM-2-12-2, to a glutarimide-based recruiter of the CRL4 CRBN ligase to effect proteosome-mediated degradation of the E protein. ZXH-2-107 (based on GNF-2) is an E-degrader with ABL inhibitory activity while ZXH-8-004 (based on CVM-2-12-2) is a selective and potent E-degrader. These two compounds provide proof of concept that difficult-to-drug targets such as a viral envelope protein can be effectively eliminated using a bivalent degrader and provide starting points for the future development of a new class of direct-acting antiviral drugs., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

There is abundant research showing the disproportionate impacts of violence on health in disadvantaged neighborhoods, making an understanding of recent violent crime trends essential for promoting health equity. Carjackings have been of particular interest in the media, although little research has been undertaken on this violent crime. We use interrupted time series models to examine the impact of the police killing of George Floyd on the spatiotemporal patterns of carjacking in Minneapolis in relation to neighborhood disadvantage. To provide grounding, we compare our results to the well-studied patterns of homicides. Results indicate that carjackings both increased and dispersed spatially after the murder of George Floyd and subsequent social unrest, more so than homicides. Socially disadvantaged neighborhoods experienced the greatest absolute increase while more advantaged neighborhoods saw a greater relative increase. The challenge ahead is to identify policy responses that will effectively curb such violence without resorting to harsh and inequitable policing and sentencing practices., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Gender-affirming top surgery is becoming increasingly common, with greater diversity in the patients receiving top surgery. The purpose of this study was to examine national trends in patient demographics, characteristics, wound complication rates, and concurrent procedures in patients receiving gender-affirming top surgeries., Methods: Patients with gender dysphoria who underwent breast procedures, including mastectomy, mastopexy, breast augmentation, or breast reduction by a plastic surgeon between 2013 and 2022, were identified from the American College of Surgeons National Surgical Quality Improvement Program database. These procedures were considered to be gender-affirming "top surgery." Univariate analyses were performed to examine trend changes in the patient population and types of additional procedures performed over the last decade., Results: There was a 38-fold increase in the number of patients who received top surgery during the most recent years compared to the first 2 years of the decade. Significantly more individuals receiving top surgery in recent years were nonbinary ( P < 0.01). There was a significant decrease in percentage of active smokers ( P < 0.01) while there was an increase in percentage of patients with diabetes ( P = 0.03). While there was a significant increase in the number of obese patients receiving top surgery ( P < 0.01), there were no differences in postoperative wound complications between the years. Significantly more patients received additional procedures ( P < 0.01) and had about a 9-fold increase in distinct number of additional CPT codes from 2013-2014 to 2021-2022., Conclusions: Our study found that there has been (1) a significant increase in the number of top surgery patients from 2013 to 2022 overall and (2) a particular increase in patients with preoperative comorbidities, such as a higher body mass index and diabetes. Understanding current and evolving trends in patients undergoing surgical treatment for gender dysphoria can inform individualized care plans that best serve the needs of patients and optimize overall outcomes., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: In-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) has become increasingly prevalent even in cases without significant male factor infertility; however, stagnant live-birth rates, both nationally and internationally, have driven more research into sperm selection. To date, nothing has replaced swim-up and density-gradient preparation methods and therefore we sought to review the state of the science., Methods: A PubMed search was performed between years of 1989 and 2024 for English research articles reporting data on sperm selection technology in assisted reproductive technology., Key Content and Findings: IVF with ICSI is increasingly prevalent even in men with normal semen parameters. Despite technologic advances and widespread use, reproductive outcomes with ICSI have been stagnant. This market for opportunity growth has allowed for sperm selection techniques to grow exponentially with heterogeneity in utilization and a paucity of positive reproductive outcomes. Swim-up and density-gradient centrifugation remain the most utilized sperm selection techniques. Various future technologies show promise including epigenetics, sperm biomarkers and a potential role of artificial intelligence; however, more research is needed., Conclusions: Given unchanged IVF success rates, sperm selection technologies hold promise to improve reproductive outcomes beyond traditional ICSI. At present, no technique has shown superiority to swim up and density centrifugation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-195/coif). R.P.S. serves as an unpaid editorial board member of Translational Andrology and Urology from August 2024 to July 2026. R.P.S. serves as Chief Medical Officer of PS Fertility. S.P. works for PS Fertility and serves on the PS Fertility Medical Advisory Board which researches the role of phosphatidylserine in sperm-egg fusion. R.P.S. and S.P. will receive Restricted Stock Unit Award of 60,000 common shares which will be vested in full in July 2026 (no stock yet vested). The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

The use of a nonrigid, pyridyldialdimine-derived macrocyclic ligand ( 3 PDAI 2 ) enabled the synthesis of well-defined mono-, di-, tri-, and tetra-nuclear Cu(I) complexes in good yields through rational synthetic means. Starting from mono- and diargentous 3 PDAI 2 complexes, transmetalation to Cu(I) proceeded smoothly with formation of AgX (X = Cl, I) salts to generate mono-, di-, and trinuclear copper complexes. Monodentate supporting ligands (MeCN, xylNC, PMe 3 , PPh 3 ) were found to either transmetallate with or bind various di- and trinuclear clusters. The solution-phase dynamic behaviors of these species were studied through NMR spectroscopic investigations, and an in-depth study of the trinuclear systems revealed a rate dependence on the identity of the supporting ligand, indicating that ligand dissociation reactions were involved in the dynamic exchange processes. Synthetic investigations further found methods for the purposeful interconversion between the di- and trinuclear systems as well as the synthesis of a pseudotetrahedral tetracopper complex with two μ-Ph supporting ligands.

Background: Readiness for return to sports involves both physical and psychological aspects of recovery; however, the relationship between psychological and physical variables after anterior cruciate ligament (ACL) reconstruction (ACLR) is poorly understood., Hypothesis: ACLR patients with a higher psychological readiness would demonstrate better functional testing results at 6 months., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Participants were evaluated at 6 months after ACLR with various patient-reported outcome metrics: Hospital for Special Surgery Pediatric Functional Activity Brief Scale, pediatric or adult International Knee Documentation Committee Questionnaire (IKDC), Patient-Reported Outcomes Measurement Information System (PROMIS) - Psychological Stress Experience and ACL - Return to Sport After Injury (ACL-RSI) scale. Functional testing included quadriceps, hamstrings, and gluteal strength testing; Y-balance test; single-leg single hop, crossover hop, and triple hop tests; and timed 6-m hop test. Pearson correlation coefficient and multivariable regression were used to determine associations between the limb symmetry index (LSI) on functional testing and patient-reported outcomes. Those with LSI deficits <20% (better performance) were compared with those with deficits >20% (worse performance)., Results: A total of 229 participants (89 male, 140 female) with a median age of 17 years (range, 10.3-30.6 years) were enrolled. IKDC had a moderate negative correlation with PROMIS - Psychological Stress Experience ( r = -0.39; 95% CI = -0.49, -0.27; P < .001) and a moderate positive correlation with ACL-RSI ( r = 0.55; 95% CI = 0.46, 0.64; P < .001). A total of 151 patients completed functional testing. ACL-RSI demonstrated a positive correlation with single-hop LSI ( r = 0.21; 95% CI = 0.05, 0.35; P = .01) and timed 6-m hop ( r = 0.28; 95% CI, 0.42; P = .001). When adjusting for sex, age, and graft type, patients who had <20% deficit on the single-hop test scored 16.6 points higher on ACL-RSI ( P = .001), and those with <20% deficit on crossover hop testing scored a mean 13.9 points higher on ACL-RSI ( P = .04)., Conclusion: Higher psychological readiness for return to sport was associated with better performance and greater symmetry on hop testing 6 months after ACLR, suggesting a potential link between physical and psychological recovery., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.D.M. has received royalties from Elsevier and serves on the board of directors for PRiSM. M.A.C. has received royalties from Springer Inc and serves on the board of directors for PRiSM. Y-M.Y. is a consultant for Smith+Nephew and serves on the editorial board for the American Journal of Sports Medicine. E.J.S. has received education payments from Smith+Nephew and hospitality payments from Stryker and Zimmer Biomet Holdings. M.S.K. has received royalties from OrthoPediatrics and education payments from Kairos Surgical. D.E.K. has received education payments from Kairos Surgical and consulting fees from DePuy Synthes Products. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Introduction: Regionalizing hepatic resections to high-volume hospitals (HVH) has improved outcomes, yet widened disparities in access. We sought to evaluate the association of hospital volume with quality care outcomes and overall survival (OS) between minor and major hepatectomy for primary liver cancer., Methods: The National Cancer Database identified patients with primary liver cancer who underwent minor/major hepatectomy (2009-2019). HVHs were defined by the top quartile in annual case volume (vs. the bottom three quartiles). Quality care outcomes (time to resection, margin status, length of stay, 30-day readmission, 30-day mortality, 90-day mortality) and OS were assessed using multivariable regression., Results: Overall, 6,988 patients underwent minor hepatectomy and 4880 major hepatectomy. No differences in quality care outcomes or OS based on hospital volume for minor hepatectomy were observed (all p > 0.05). Treatment at HVHs for major hepatectomy was associated with decreased odds of 30-day and 90-day mortality events (all p < 0.05). Median OS was 40.2 months [IQR 21.7-66.6] at HVHs versus 33.5 [IQR 17.0-58.7] at low-volume hospitals which remained independently predictive of improved OS on multivariable analysis (HR 0.86, 95% CI 0.79-0.93)., Conclusion: These results support regionalization to HVHs for major hepatectomy; however, minor hepatectomy can be safely performed at hospitals regardless of volume., (© 2024 Wiley Periodicals LLC.)

Background: One third of organ donors suffer catastrophic brain injury (CBI). There are no standard guidelines for the management of traumatic CBI prior to brain death, and not all trauma centers have institutional CBI guidelines. In addition, there is high variability in management between institutions with guidelines. Catastrophic brain injury guidelines vary and may include various combinations of hormone therapy, vasopressors, fluid resuscitation, and other practices. We hypothesized that centers with CBI guidelines have higher organ donation rates than those without., Methods: This prospective, observational EAST-sponsored multicenter trial included adult (18+ years old) traumatic-mechanism CBI patients at 33 level I and II trauma centers from January 2022 to May 2023. Catastrophic brain injury was defined as a brain injury causing loss of function above the brain stem and subsequent death. Cluster analysis with linear mixed-effects model including UNOS regions and hospital size by bed count was used to determine whether CBI guidelines are associated with organ donation., Results: A total of 790 CBI patients were included in this analysis. In unadjusted comparison, CBI guideline centers had higher rates of organ donation and use of steroids, whole blood, and hormone therapy. In a linear mixed-effects model, CBI guidelines were not associated with organ donation. Registered organ donor status, steroid hormones, and vasopressin were associated with increased relative risk of donation., Conclusion: There is high variability in management of CBI, even at centers with CBI guidelines in place. While the use of institutional CBI guidelines was not associated with increased organ donation, guidelines in this study were not identical. Hormone replacement with steroids and vasopressin was associated with increased donation. Hormone resuscitation is a common feature of CBI guidelines. Further analysis of individual practices that increase organ donation after CBI may allow for more effective guidelines and an overall increase in donation to decrease the long waiting periods for organ transplant recipients., Level of Evidence: Prognostic; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Congenital adrenal hyperplasia has been reported to manifest with white matter aberrations. However, many previous studies included only small samples, restricted their analyses to females, lacked a control group and/or did not correct for brain size. Here, we examined the largest sample to date, comprising 53 male and female participants with congenital adrenal hyperplasia, who were matched with 53 male and female controls in terms of sex, age, education, and verbal intelligence. The four groups were compared with respect to their total white matter as well as white matter hyperintensities while applying brain size corrections. For both measures, total white matter and white matter hyperintensities, there were no significant sex differences or group-by-sex interactions. However, individuals with congenital adrenal hyperplasia had significantly smaller total white matter volumes compared to controls. Our findings align with previous reports of white matter variations in congenital adrenal hyperplasia. The absence of a group-by-sex interaction suggests that white matter variations in congenital adrenal hyperplasia may not be attributable to prenatal androgens. Instead, they may be a result of the condition itself and/or its treatment with glucocorticoids. The latter aspect warrants follow-up, particularly given that glucocorticoids are employed not only in congenital adrenal hyperplasia but also in other medical conditions., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Competing Interests: Potential Conflicts of Interest and Funding Sources: This study did not receive any funding. The authors do not have any conflicts of interest to declare.