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Abstract Background Research on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited. Methods Data from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed. Results During a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene. Conclusion Calcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.

Abstract Background The net benefit of aspirin cessation in older adults remains uncertain. This study aimed to use observational data to emulate a randomized trial of aspirin cessation versus continuation in older adults without cardiovascular disease (CVD). Methods Post hoc analysis using a target trial emulation framework applied to the immediate post-trial period (2017–2021) of a study of low-dose aspirin initiation in adults aged ≥ 70 years (ASPREE; NCT01038583). Participants from Australia and the USA were included if they were free of CVD at the start of the post-trial intervention period (time zero, T0) and had been taking open-label or randomized aspirin immediately before T0. The two groups in the target trial were as follows: aspirin cessation (participants who were taking randomized aspirin immediately before T0; assumed to have stopped at T0 as instructed) versus aspirin continuation (participants on open-label aspirin at T0 regardless of their randomized treatment; assumed to have continued at T0). The outcomes after T0 were incident CVD, major adverse cardiovascular events (MACE), all-cause mortality, and major bleeding during 3, 6, and 12 months (short-term) and 48 months (long-term) follow-up. Hazard ratios (HRs) comparing aspirin cessation to continuation were estimated from propensity-score (PS) adjusted Cox proportional-hazards regression models. Results We included 6103 CVD-free participants (cessation: 5427, continuation: 676). Over both short- and long-term follow-up, aspirin cessation versus continuation was not associated with elevated risk of CVD, MACE, and all-cause mortality (HRs, at 3 and 48 months respectively, were 1.23 and 0.73 for CVD, 1.11 and 0.84 for MACE, and 0.23 and 0.79 for all-cause mortality, p > 0.05), but cessation had a reduced risk of incident major bleeding events (HRs at 3 and 48 months, 0.16 and 0.63, p

Background and aims Gallstone disease affects ≥40 million people in the USA and accounts for health costs of ≥$4 billion a year. Risk factors such as obesity and metabolic syndrome are well established. However, data are limited on relevant metabolomic alterations that could offer mechanistic and predictive insights into gallstone disease. This study prospectively identifies and externally validates circulating prediagnostic metabolites associated with incident gallstone disease.Methods Female participants in Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHS II) who were free of known gallstones (N=9960) were prospectively followed up after baseline metabolomic profiling with liquid chromatography–tandem mass spectrometry. Multivariable logistic regression and enrichment analysis were used to identify metabolites and metabolite groups associated with incident gallstone disease at PFDR

Dietary patterns contribute to overall health and diseases of ageing but are understudied in older adults. As such, we first aimed to develop dietary indices to quantify Mediterranean Diet Score (MDS) utilisation and Ultra-processed Food (UPF) intake in a well-characterised cohort of relatively healthy community-dwelling older Australian adults. Second, we aimed to understand the relationship between these scores and the association of these scores with prevalent cardiometabolic disease and frailty. Our major findings are that in this population of older adults, (a) pre-frailty and frailty are associated with reduced MDS and increased UPF intake; (b) adherence to MDS eating patterns does not preclude relatively high intake of UPF (and vice versa); and (c) high utilisation of an MDS eating pattern does not prevent an increased risk of frailty with higher UPF intakes. As such, the Mediterranean Diet pattern should be encouraged in older adults to potentially reduce the risk of frailty, while the impact of UPF intake should be further explored given the convenience these foods provide to a population whose access to unprocessed food may be limited due to socioeconomic, health, and lifestyle factors.

Abstract The transmembrane death receptor Fas transduces apoptotic signals upon binding its ligand, FasL. Although Fas is highly expressed in cancer cells, insufficient cell surface Fas expression desensitizes cancer cells to Fas-induced apoptosis. Here, we show that the increase in Fas microaggregate formation on the plasma membrane in response to the inhibition of endocytosis sensitizes cancer cells to Fas-induced apoptosis. We used a clinically accessible Rho-kinase inhibitor, fasudil, that reduces endocytosis dynamics by increasing plasma membrane tension. In combination with exogenous soluble FasL (sFasL), fasudil promoted cancer cell apoptosis, but this collaborative effect was substantially weaker in nonmalignant cells. The combination of sFasL and fasudil prevented glioblastoma cell growth in embryonic stem cell-derived brain organoids and induced tumor regression in a xenograft mouse model. Our results demonstrate that sFasL has strong potential for apoptosis-directed cancer therapy when Fas microaggregate formation is augmented by mechano-inhibition of endocytosis.

Traditional map projections introduce distortions, especially for global data. Discrete Global Grid Systems (DGGS) offer an alternative by dividing the Earth into equal-area grid cells at different resolutions. This paper describes xdggs, a new Xarray extension that simplifies working with DGGS. Xdggs provides a unified API for various DGGS libraries and integrates seamlessly with the Pangeo ecosystem through extending the widely used Xarray library to use the DGGS-specific cell identifiers as an index. This development makes DGGS more accessible and will lead to facilitating data analysis on a planetary scale.Xdggs aims to provide a user-friendly API that hides the implementation complexities of different DGGS libraries. And because it integrates seamlessly with Xarray, a popular tool for geospatial data analysis, xdggs promotes FAIR data practices by simplifying data access and interoperability and can become a valuable tool for geospatial scientists and application developers working with global datasets.

Abstract In systems exhibiting the non-Hermitian skin effect (NHSE), the bulk spectrum under open boundary conditions (OBC) significantly differs from that of its periodic counterpart. This disparity renders the conventional bulk-boundary correspondence (BBC) inapplicable. Here we propose an intuitive approach called doubling and swapping to restore the BBC, using the non-Hermitian Su-Schrieffer-Heeger model as an example. Explicitly, we construct a modified system free of NHSE by swapping the asymmetric intracell hoppings in every second primitive unit cell. Importantly, this change does not alter the OBC spectrum. As a result, the modified periodic system can serve as the bulk for defining topological invariants that accurately predict edge states and topological phase transitions. The basic principle is applicable to many other systems. By extending the study to disordered systems in which the asymmetric hoppings are randomly swapped, we show that two types of winding numbers can also be defined to account for the NHSE and topological edge states, respectively.

Abstract The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large prospective cohort, we performed shotgun metagenomic sequencing and untargeted metabolomics profiling among 121 women diagnosed with diverticulitis requiring antibiotics or hospitalizations (cases), matched to 121 women without diverticulitis (controls) according to age and race. Overall microbial community structure and metabolomic profiles differed in diverticulitis cases compared to controls, including enrichment of pro-inflammatory Ruminococcus gnavus, 1,7-dimethyluric acid, and histidine-related metabolites, and depletion of butyrate-producing bacteria and anti-inflammatory ceramides. Through integrated multi-omic analysis, we detected covarying microbial and metabolic features, such as Bilophila wadsworthia and bile acids, specific to diverticulitis. Additionally, we observed that microbial composition modulated the protective association between a prudent fiber-rich diet and diverticulitis. Our findings offer insights into the perturbations in inflammation-related microbial and metabolic signatures associated with diverticulitis, supporting the potential of microbial-based diagnostics and therapeutic targets.

Abstract Objective To evaluate the contribution of germline genetics to regulating the briskness and diversity of T cell responses in CRC, we conducted a genome-wide association study to examine the associations between germline genetic variation and quantitative measures of T cell landscapes in 2,876 colorectal tumors from participants in the Molecular Epidemiology of Colorectal Cancer Study (MECC). Methods Germline DNA samples were genotyped and imputed using genome-wide arrays. Tumor DNA samples were extracted from paraffin blocks, and T cell receptor clonality and abundance were quantified by immunoSEQ (Adaptive Biotechnologies, Seattle, WA). Tumor infiltrating lymphocytes per high powered field (TILs/hpf) were scored by a gastrointestinal pathologist. Regression models were used to evaluate the associations between each variant and the three T-cell features, adjusting for sex, age, genotyping platform, and global ancestry. Three independent datasets were used for replication. Results We identified a SNP (rs4918567) near RBM20 associated with clonality at a genome-wide significant threshold of 5 × 10− 8, with a consistent direction of association in both discovery and replication datasets. Expression quantitative trait (eQTL) analyses and in silico functional annotation for these loci provided insights into potential functional roles, including a statistically significant eQTL between the T allele at rs4918567 and higher expression of ADRA2A (P = 0.012) in healthy colon mucosa. Conclusions Our study suggests that germline genetic variation is associated with the quantity and diversity of adaptive immune responses in CRC. Further studies are warranted to replicate these findings in additional samples and to investigate functional genomic mechanisms.

Abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

Abstract A boundary mode localized on one side of a finite-size lattice can tunnel to the opposite side which results in unwanted couplings. Conventional wisdom tells that the tunneling probability decays exponentially with the size of the system which thus requires many lattice sites before eventually becoming negligibly small. Here we show that the tunneling probability for some boundary modes can apparently vanish at specific wavevectors. Thus, similar to bound states in the continuum, a boundary mode can be completely trapped within very few lattice sites where the bulk bandgap is not even well-defined. More intriguingly, the number of trapped states equals the number of lattice sites along the normal direction of the boundary. We provide two configurations and validate the existence of this peculiar finite barrier-bound state experimentally in a dielectric photonic crystal at microwave frequencies. Our work offers extreme flexibility in tuning the coupling between localized states and channels as well as a new mechanism that facilitates unprecedented manipulation of light.

Summary: Background: Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations. Methods: A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously. Findings: The 3-DF joint test revealed two significant loci with p-value

Summary: Background: Ultra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored. Methods: Data collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I–III CRC within the Nurses’ Health Study and Health Professionals Follow-up Study during 1980–2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders. Findings: The mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths were documented, including 321 from CRC and 335 from CVD. Compared to those in the lowest quintile (median = 3.6 servings/d), patients in the highest quintile (median = 10 servings/d) of post-diagnostic UPF intake had higher CVD mortality (HR = 1.65, 95% CI = 1.13–2.40) but not CRC or all-cause mortality. Among UPF subgroups, higher consumption of fats/condiments/sauces was associated with a higher risk of CVD-specific mortality (highest vs. lowest quintile of intake, HR = 1.96, 95% CI = 1.41–2.73), and higher intake of ice cream/sherbet was associated with an increased risk of CRC-specific mortality (highest vs. lowest quintile, HR = 1.86, 95% CI: 1.33–2.61). No statistically significant association was found between UPF subgroups and overall mortality. Interpretation: Higher post-diagnostic intake of total UPFs and fats/condiments/sauces in CRC survivors is associated with higher CVD mortality, and higher ice cream/sherbet intake is linked to higher CRC mortality. Funding: US National Institutes of Health and the American Cancer Society.

Boundary modes localized on the boundaries of a finite-size lattice experience a finite size effect (FSE) that could result in unwanted couplings, crosstalks and formation of gaps even in topological boundary modes. It is commonly believed that the FSE decays exponentially with the size of the system and thus requires many lattice sites before eventually becoming negligibly small. Here we consider a two-dimensional strip geometry that is periodic along one direction and truncated along the other direction, in which we identify a special type of FSE of some boundary modes that apparently vanishes at some particular wave vectors along the periodic direction. Meanwhile, the number of wave vectors where the FSE vanishes equals the number of lattice sites across the strip. We analytically prove this type of FSE in a simple model and prove this peculiar feature. We also provide a physical system consisting of a plasmonic sphere array where this FSE is present. Our work points to the possibility of almost arbitrarily tunning of the FSE, which facilitates unprecedented manipulation of the coupling strength between modes or channels such as the integration of multiple waveguides and photonic non-abelian braiding.

Blood pressure (BP) levels are important modifiable risk factors for incident cardiovascular disease (CVD). However, many adults are on anti-hypertensive medication (MEDS) which lowers their BP but is a marker for increased CVD risk. To capture the association of BP and its treatment with risk, it is important to estimate BP levels in the absence of medication, i.e., Underlying BP. One proposed ad-hoc solution is to add a fixed increment e.g., 10/5 mm Hg to systolic (SBP)/diastolic (DBP) for people on MEDS to approximate their Underlying BP. However, what this increment should be, and whether it applies to all MEDS users is unclear. In this manuscript, we propose a novel time-to-event approach to estimate Underlying BP, treating BPs on MEDS as censored observations. The results indicate that the median Treatment Effect (i.e., Underlying BP - Observed BP) for SBP/DBP is 12.0/7.7 for men and 16.9/6.5 for women and is significantly modified by age, BMI and black race. The Underlying BP for MEDS users is then combined with the observed BP for non-MEDS users to derive age-sex-specific BP percentiles for Underlying BP based on a representative sample of normal weight U.S. adults aged 18-79 using NHANES data from 1999-2018., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: The Pediatric Cardiac Critical Care Consortium (PC4) cardiac arrest prevention (CAP) quality improvement (QI) project facilitated a decreased in-hospital cardiac arrest (IHCA) incidence rate across multiple hospitals. The sustainability of this outcome has not been determined., Objective: To examine the IHCA incidence rate at participating hospitals after the QI project ended and discern which factors best aligned with sustained improvement., Design, Setting, and Participants: This observational cohort study compared IHCA data from the CAP era (July 1, 2018, to December 31, 2019) with data from the 2-year follow-up era (March 1, 2020, to February 28, 2022). Data were obtained from pediatric cardiac intensive care units (CICUs) from 17 PC4 CAP-participating hospitals., Intervention: The CAP practice bundle was designed to facilitate local practice integration, with the intention to implement, adapt, and continue CAP processes beyond the CAP era. A web-based survey was administered 2 years after the end of the project to estimate CAP-specific QI work., Main Outcomes and Measures: Risk-adjusted IHCA incidence rates across all admissions were compared between study eras. The survey generated a novel hospital-specific QI sustainability score, which is generally reflective of the sum of local CAP work performed., Results: There were no clinically important differences in demographic and admission characteristics between the 13 082 CAP era admissions and 16 284 follow-up admissions (total mean [SD] age, 5.1 [8.4] years; 56.1% male). Risk-adjusted IHCA incidences were not different between the CAP vs follow-up eras (2.8% vs 2.8%; odds ratio, 1.03; 95% CI, 0.89-1.19), suggesting sustained prevention improvement. There was also no difference between eras in risk-adjusted IHCA incidence within medical, surgical, or high-risk subgroups. A lower hospital QI sustainability score was correlated with higher odds for IHCA in the follow-up vs CAP era (correlation coefficient, -0.58; P = .02). Five hospitals had increases of 1% or greater in risk-adjusted IHCA rates in the follow-up era; these hospitals had significantly lower QI sustainability scores and were less likely to have adopted sustainability elements during the CAP era or report persistent engagement for CAP-related QI processes during follow-up., Conclusions and Relevance: In this cohort study of all CICU admissions across 17 hospitals, IHCA prevention was feasible and sustainable; the established reduction in risk-adjusted IHCA rate was maintained for at least 2 years after the end of the CAP project. Both implementation strategies and continued engagement in CAP processes during the follow-up era were associated with sustained improvement.

Race-conscious research identifies health disparities with 1) rigorous and responsible data collection, 2) intentionality and considered analyses, and 3) interpretation of results that advance health equity. Individual registries must overcome specific challenges to promote race-conscious research, and this paper describes ways to achieve this with a focus on the international Extracorporeal Life Support Organization (ELSO) registry. This article reviews ELSO registry publications that studied race with outcomes to consider whether research outputs align with race-conscious concepts and describe the direction of associations reported. Studies were identified via secondary analysis of a comprehensive scoping review on ECMO disparities. Of 32 multicenter publications, two (6%) studied race as the primary objective. Statistical analyses, confounder adjustment, and inclusive, antibiased language were inconsistently used. Only two (6%) papers explicitly discussed mechanistic drivers of inequity such as structural racism, and five (16%) discussed race variable limitations or acknowledged unmeasured confounders. Extracorporeal Life Support Organization registry publications demonstrated more adverse ECMO outcomes for underrepresented/minoritized populations than non-ELSO studies. With the objective to promote race-conscious ELSO registry research outputs, we provide a comprehensive understanding of race variable limitations, suggest reasoned retrospective analytic approaches, offer ways to interpret results that advance health equity, and recommend practice modifications for data collection., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Background: Gaps between educational preparation and clinical practice readiness have led to innovative approaches to competence assessment. Entrustable professional activities (EPAs) show promise as a competence assessment framework in graduate nursing education., Purpose: This study sought to develop and validate a set of EPAs that reflect the core activities performed by all nurse practitioners (NPs)., Methods: Eight EPAs were developed. A Delphi approach was used to validate the EPAs by NP practice experts located across the United States and representing most NP populations., Results: Consensus was reached after 2 Delphi rounds., Conclusions: The EPAs developed and validated in this study map multiple advanced-level NP competencies to workplace expectations and provide a shared framework for competency-based workplace assessment among NP preceptors from varied health care professions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adolescents and young adults (AYA) living with HIV have been shown to have lower rates of viral load testing and viral suppression as compared to older adults. We examined trends over time and predictors of HIV viral load monitoring and viral suppression among AYA in a large HIV treatment programme in Dar es Salaam, Tanzania., Methods: We analysed longitudinal data of AYA aged 10-24 years initiated on antiretroviral therapy between January 2017 and October 2022. Trend models were used to assess changes in HIV viral load testing and viral suppression by calendar year. Generalised estimating equations were used to examine the relationship of sociodemographic and clinical factors with HIV viral load testing and viral suppression., Results: Out of 15,759 AYA, the percentage of those who received a 6-month HIV viral load testing increased from 40.6% in 2017 to 64.7% in 2022 and, a notable annual increase of 5.6% (p < 0.001). A higher HIV viral load testing uptake was observed among 20- to 24-year-olds (87.7%) compared to 10- to 19-year-olds (80.2%) (p < 0.001). The likelihood of not receiving an HIV viral load test within 12 months of antiretroviral therapy initiation was higher among 10- to 19-year-olds (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI] = 1.4-2.0), advanced HIV disease (aOR = 1.3; 95% CI = 1.12-1.53), normal nutrition status at enrolment aOR 2.6 (95% CI = 1.59-4.26) and initiation of non-nucleoside reverse transcriptase inhibitors regimen aOR 1.2 (95% CI = 1.08-1.34). The proportion of AYA with viral suppression increased from 83.0% in 2017 to 94.6% in 2022. Notably, the overall trend in viral suppression increased significantly at 2.4% annually. The risk of not achieving viral suppression was greater among 10- to 14-year-olds (aOR = 2; 95% CI = 1.75-2.43) and 15- to 19-year-olds (aOR = 1.4; 95% CI = 1.24-1.58) as compared to 20-24 years; being male (aOR = 1.16; 95% CI = 1.02-1.32); undernourished (aOR = 1.53; 95% CI = 1.17-1.99); in WHO Stage II (aOR = 1.16; 95% CI = 1.02-1.33) and III (aOR = 1.21; 95% CI = 1.03-1.42) and being on an non-nucleoside reverse transcriptase inhibitors regimen (aOR = 1.32; 95% CI = 1.18-1.48)., Conclusion: HIV viral load testing uptake at 6 months of antiretroviral therapy initiation and viral suppression increased from 2017 to 2022; however, overall HIV viral load testing was suboptimal. Demographic and clinical characteristics can be used to identify AYA at greater risk for not having HIV viral load test and not achieving viral suppression., (© 2024 John Wiley & Sons Ltd.)

Urothelial carcinoma (UC) occurs uncommonly in cats and no association has previously been observed with long-term indwelling urinary implants. An 18-year-old male castrated domestic shorthair cat initially was presented for hematuria, leading to the diagnosis of a right-sided ureterolithiasis and severe pyelectasia on ultrasound examination, prompting right-sided subcutaneous ureteral bypass (SUB) device placement. The cat subsequently had intermittent hematuria and dysuria, without ultrasonographic abnormality of the bladder or positive urine culture. Thirteen months later the patient developed refractory lower urinary tract signs, azotemia, a proliferative mass in the region of the cystostomy tube component of the SUB device and evidence of left ureteral obstruction. Cystostomy tube revision and left-sided SUB device placement were performed, as well as a partial cystectomy for removal of the mass. Upon histopathology, the mass was diagnosed as a UC. To our knowledge, UC associated with a long-term indwelling cystostomy catheter component of a SUB device has not been reported in veterinary medicine., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background The use of bendamustine with an anti-CD20 monoclonal antibody as frontline therapy for indolent non-Hodgkin lymphoma (NHL) has become a standard of care. We aimed to evaluate the real-world efficacy and safety of bendamustine-rituximab (BR) frontline therapy for indolent NHL. Patients and methods Patients with indolent NHL treated with frontline BR therapy in Hôpital du Sacré-Coeur de Montréal, from January 2015 to August 2018 were included in this retrospective study. Results Our cohort included 42 adults with a median age of 63 years. Follicular lymphoma was the most common histology (n = 31, 74%). Most patients had advanced disease (Lugano stage III or IV, 88%). The overall response rate was 84% (complete response = 62% and partial response = 22%). Median progression-free survival (PFS) was not reached. At 30 months, PFS was 74.8% and overall survival was 90%. Grade 3-4 neutropenia occurred in 21% of patients. Infection-related adverse events were observed in 17 patients (40%). Most were grade 1 and 2 events (84%). One case of grade 5 progressive multifocal leukoencephalopathy related to John Cunningham (JC) virus reactivation was observed. The most common non-infectious-related adverse events were mild nausea and fatigue. Conclusions The efficacy and safety of BR treatment for indolent NHL were comparable in our real-life cohort compared to prior studies. This supports BR as a standard of care for indolent NHL. Future studies should assess whether the use of granulocyte-colony stimulating factors as primary prophylaxis effectively mitigates the hematological and infection-related adverse events related to BR therapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Comité d'éthique de la recherche du CIUSSS du Nord-de-l'Île-de-Montréal issued approval 2020-1931. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: Jean-Samuel Boudreault: AbbVie, Janssen, Pfizer, and Sanofi. The other authors declare no conflict of interest., (Copyright © 2024, Chan et al.)

We present the case of an infant with rapidly progressing orbital tumor that had initial radiological and clinical features of both rhabdomyosarcoma and capillary hemangioma. The patient was eventually diagnosed with malignant rhabdoid tumor of the orbit. We discuss the salient histological and radiological features of our case and review the literature on orbital malignant rhabdoid tumors., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Psychological stress during pregnancy is known to have a range of long-lasting negative consequences on the development and health of offspring. Here, we tested whether a measure of prenatal early-life stress was associated with a biomarker of physiological development at birth, namely epigenetic gestational age, using foetal cord-blood DNA-methylation data. Longitudinal cohorts from the Netherlands (Generation R Study [Generation R], n = 1,396), the UK (British Avon Longitudinal Study of Parents and Children [ALSPAC], n = 642), and Norway (Mother, Father and Child Cohort Study [MoBa], n1 = 1,212 and n2 = 678) provided data on prenatal maternal stress and genome-wide DNA methylation from cord blood and were meta-analysed (pooled n = 3,928). Measures of epigenetic age acceleration were calculated using three different gestational epigenetic clocks: "Bohlin", "EPIC overlap" and "Knight". Prenatal stress exposure, examined as an overall cumulative score, was not significantly associated with epigenetically-estimated gestational age acceleration or deceleration in any of the clocks, based on the results of the pooled meta-analysis or those of the individual cohorts. No significant associations were identified with specific domains of prenatal stress exposure, including negative life events, contextual (socio-economic) stressors, parental risks (e.g., maternal psychopathology) and interpersonal risks (e.g., family conflict). Further, no significant associations were identified when analyses were stratified by sex. Overall, we find little support that prenatal psychosocial stress is associated with variation in epigenetic age at birth within the general paediatric population., Competing Interests: Additional Declarations: The authors have declared there is NO conflict of interest to disclose

The modified Lapidus procedure has emerged as a versatile solution for various pedal pathologies, particularly hallux abducto valgus. There have been numerous modifications over time regarding fixation techniques, joint preparation methods, graft utilization, and weightbearing protocols. However, concerns persist regarding prolonged nonweightbearing postoperatively, prompting the need for alternative approaches. This retrospective descriptive cohort analysis assessed the outcomes of 40 feet from 34 patients who underwent the modified Lapidus procedure with a medial plating system, aimed to evaluate immediate weightbearing outcomes on union rate, fixation-related complications, and functional outcomes. Among the 40 feet, findings showed a 95% (38/40) union rate within 6 months, with 2.5% (1/40) experiencing delayed union and 2.5% (1/40) facing fixation-related complications. There is a single case of malunion in the cohort. Additionally, statistically significant improvements were observed across all domains of the Manchester-Oxford Foot Questionnaire at p < .001. These findings suggest immediate weightbearing as a potential alternative to traditional nonweightbearing protocols. However, the study's retrospective nature and lack of a comparative group warrant cautious interpretation. Further research is essential to validate these findings and refine postoperative care protocols. By challenging conventional practices, this study underscores the complexity of optimizing patient outcomes in modified Lapidus procedure management. Tailored approaches and prospective investigations are imperative for establishing definitive guidelines and enhancing surgical techniques in this domain., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Despite improvement in hemodynamics, children with single ventricle heart disease remain on feeding tubes long after stage 2 palliation (S2P). Use of a hunger provocation method in a multidisciplinary team setting has been successful at weaning these children from feeding tubes. The objective of this study is to describe patient characteristics and outcomes in the single ventricle population who underwent a formal tube weaning process using a standardized hunger provocation method. Single ventricle patients after S2P from six centers were included. Patient data collected included baseline demographics, swallow evaluation results, and feeding characteristics such as percent oral intake at the start of tube wean. Tube wean data included tube weaning process and duration, interruptions to the tube wean, adverse events, and weights before, during, and after the tube wean. 94% (60 of 64) of patients achieved oral independence. The median time to tube wean was 12.5 days. 62% of patients had transient weight loss during the tube wean. 61% of the cohort was taking less than 10% goal volumes by mouth with 90% of those patients successfully tube weaned. All patients with history of aspiration were successfully tube weaned. 75% of successfully weaned patients were above baseline weight at 1-month post-tube wean. The most common cause of tube wean interruption was contraction of a viral illness. Use of a standardized tube weaning process via hunger provocation method is both feasible and safe in the single ventricle population, resulting in successful feeding tube removal in a timely manner with minimal adverse effects., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Proteasomes degrade intracellular proteins to generate antigenic peptides that are recognized by the adaptive immune system and promote anticancer immunity. However, tumors subvert the antigen presentation machinery to escape immunosurveillance. We hypothesized that proteasome activation could concomitantly increase antigen abundance and diversity in multiple myeloma cells. High-throughput screens revealed that histone deacetylase 6 (HDAC6) inhibitors activated proteasomes to unmask neoantigens and amplify the tumor-specific antigenic landscape. Treatment of patient CD138+ cells with HDAC6 inhibitors significantly promoted the antimyeloma activity of autologous CD8+ T cells. Pharmacologic blockade and genetic ablation of the HDAC6 ubiquitin-binding domain released HR23B, which shuttles ubiquitinylated cargo to proteasomes, while silencing HDAC6 or HR23B in multiple myeloma cells abolished the effect of HDAC6 inhibitors on proteasomes, antigen presentation, and T-cell cytotoxicity. Taken together, our results demonstrate the paradigm-shifting translational impact of proteasome activators to expand the myeloma immunopeptidome and have revealed novel, actionable antigenic targets for T cell-directed immunotherapy., Significance: The elimination of therapy-resistant tumor cells remains a major challenge in the treatment of multiple myeloma. Our study identifies and functionally validates agents that amplify MHC class I-presented antigens and pave the way for the development of proteasome activators as immune adjuvants to enhance immunotherapeutic responses in patients with multiple myeloma., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: The Nominal Group Technique (NGT) is a consensus group method used to synthesize expert opinions. Given the global shift to virtual meetings, the extent to which researchers leveraged virtual platforms is unclear. This scoping review explores the use of the vNGT in healthcare research during the COVID-19 pandemic., Methods: Following the Arksey and O'Malley's framework, eight cross-disciplinary databases were searched (January 2020-July 2022). Research articles that reported all four vNGT stages (idea generation, round robin sharing, clarification, voting) were included. Media Synchronicity Theory informed analysis. Corresponding authors were surveyed for additional information., Results: Of 2,589 citations, 32 references were included. Articles covered healthcare (27/32) and healthcare education (4/32). Platforms used most were Zoom, MS Teams and GoTo but was not reported in 44% of studies. Only 22% commented on the benefits/challenges of moving the NGT virtually. Among authors who responded to our survey (16/32), 80% felt that the vNGT was comparable or superior., Conclusions: The vNGT provides several advantages such as the inclusion of geographically dispersed participants, scheduling flexibility and cost savings. It is a promising alternative to the traditional in-person meeting, but researchers should carefully describe modifications, potential limitations, and impact on results., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee 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.)

Background: Children undergoing cardiac surgical procedures may require postoperative surgical or catheter-based reintervention before discharge. We examined racial/ethnic variations in reintervention and associated in-hospital death., Methods: Children undergoing cardiac surgical procedures from 2004 to 2015 were identified in the Pediatric Health Information Systems (PHIS) database. Regression analysis measured associations between race/ethnicity, in-hospital death, and postoperative cardiac surgical or catheter-based reintervention (surgical/catheter reintervention)., Results: Of 124,263 patients, 8265 (6.7%) had a surgical/catheter reintervention. Black patients had fewer reinterventions (5.9% vs 6.7%) and higher in-hospital mortality (3.9% vs 2.7%, P < .01) than White patients. After adjusting for sociodemographic and illness severity indicators, Black patients remained less likely to receive surgical/catheter reintervention (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.82-0.98) despite having similar risk of death after reintervention (adjusted odds ratio, 1.17; 95% CI, 0.98-1.41) compared with White patients. The risk of death without surgical/catheter reintervention was also higher for Black (aHR, 1.26; 95% CI, 1.08-1.47) and other race/ethnicity (aHR, 1.33; 95% CI, 1.13-1.57) patients than for White patients. Similar trends were demonstrated when mechanical circulatory support and cardiac transplantation were included as reinterventions., Conclusions: Patients of Black and other race/ethnicity undergoing pediatric cardiac surgical procedures are more likely to die without postoperative cardiac reintervention than White patients. Black patients are also less likely to receive reintervention despite no significant difference in mortality with reintervention. Further studies should evaluate etiologies and methods of addressing these disparities., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint target; however, the downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) as a VISTA binding partner, which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell-specific LRIG1 deletion developed superior antitumor responses because of expansion of tumor-specific cytotoxic T lymphocytes (CTLs) with increased effector function and survival. Sustained tumor control was associated with a reduction of quiescent CTLs (TCF1 + CD62L hi PD-1 low ) and a reciprocal increase in progenitor and memory-like CTLs (TCF1 + PD-1 + ). In patients with melanoma, elevated LRIG1 expression on tumor-infiltrating CD8 + CTLs correlated with resistance to immunotherapies. These results delineate the role of LRIG1 as an inhibitory immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.

Diffusion-weighted imaging is increasingly available for brain investigation. Image interpretation of intracranial space-occupying lesions often includes the derived apparent diffusion coefficient (ADC) analysis. In human medicine, ADC can help discriminate between benign and malignant lesions in intracranial tumors. This study investigates the difference in ADC values depending on the sample strategies of image analysis. MRI examination, including diffusion-weighted images of canine and feline patients presented between 2015 and 2020, were reviewed retrospectively. Patients with single, large intracranial space-occupying lesions were included. Lesions homogeneity was subjectively scored. ADC values were calculated using six different methods of sampling (M1-M6) on the ADC map. M1 included as much as possible of the lesion on a maximum of five consecutive slices; M2 included five central and five peripheral ROIs; M3 included a single ROI on the solid part of the lesion; M4 included three central ROIs on one slice; M5 included three central ROIs on different slices; and M6 included one large ROI on the entire lesion. A total of 201 animals of various breeds, genders, and ages were analyzed. ADC values differed significantly between M5 against M2 (peripheral) ( p  < 0.001), M5 against M6 ( p  = 0.009), and M4 against M2 (peripheral) ( p  = 0.005). When lesions scored as homogeneous in all sequences were excluded, an additional significant difference in three further sampling methods was present ( p  < 0.005). ADC of single, large, intracranial space-occupying lesions differed significantly in half of the tested methods of sampling. Excluding homogeneous lesions, additional significant differences among the sampling methods were present. The obtained results should increase awareness of the variability of the ADC, depending on the sample strategies used., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chan, Richter and Del Chicca.)

Post bariatric hypoglycaemia (PBH) is typically a post-prandial hypoglycaemia occurring about 2-4 hours after eating in people who have undergone bariatric surgery. PBH develops relatively late after surgery and often after discharge from post-surgical follow-up by bariatric teams, leading to variability in diagnosis and management in non-specialist centres., Aim: to improve and standardise clinical practice in the diagnosis and management of PBH., Objectives: (1) to undertake an up-to-date review of the current literature; (2) to formulate practical and evidence-based guidance with regards on the diagnosis and treatment of PBH; (3) to recommend future avenues for research in this condition., Method: A scoping review was undertaken after an extensive literature search. A consensus on the guidance and confidence in the recommendations was reached by the steering group authors prior to review by key stakeholders., Outcome: We make pragmatic recommendations for the practical diagnosis and management of PBH including criteria for diagnosis and recognition, as well as recommendations for research areas that should be explored.

Background: Unilateral vocal fold immobility (VFI) is a known cause of morbidity amongst children following congenital heart surgery. Injection medialization (IM) provides medial distraction and improves glottic closure. Limited objective data is available for the effect of IM in young children (<2 years-old) with VFI., Methods: Retrospective case series of infants <2 who underwent IM for VFI after congenital cardiac surgery. Primary outcome was objective reduced risk of aspiration based on Dysphagia and Outcome Severity Scores (DOSS) on Video swallow study (VFSS) performed prior to and within 4 weeks following IM. Secondary analysis included perioperative complications and number of children who were able to avoid NG or G tube placement., Results: 17 children <2 years of age had unilateral VFI after congenital cardiac surgery and underwent IM. The median age at time of initial cardiac surgery was 6 days (IQR 3-7). There was no intraoperative or postoperative stridor or associated complications. All 17 patients had preoperative aspiration noted on VFSS. Average swallowing outcomes on VFSS improved after IM with an increase in DOSS score (preop score 3 (IQR 2-4) to postop score 6.5 (IQR 5-7) [P = 0.001]). At 2 months following IM, of the patients who had improvement in swallowing function, 50% (n = 6) were able to feed completely orally, 25% (n = 3) were fed orally with an NG wean, and 3 (25%) had a G tube placed., Conclusion: Initial results suggest that IM is safe and improves early objective swallowing outcomes in children <2 years old with VFI after congenital cardiac surgery., Level of Evidence: IV Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: In patients undergoing hypoglossal nerve stimulation (HGNS), we examined the Insomnia Severity Index (ISI) to understand how baseline sleep onset insomnia (SOI), sleep maintenance insomnia (SMI), and early morning awakening (EMA) affected postsurgical outcomes., Study Design: Observational., Setting: Multicenter registry., Methods: We included patients from the Adherence and Outcomes of Upper Airway Stimulation for Obstructive Sleep Apnea International Registry (ADHERE) with a baseline ISI from 2020 to 2023. Regression analysis examined the association of ISI question scores for SOI, SMI, and EMA and outcomes: Apnea-Hypopnea Index (AHI) reduction, device usage, changes in the Epworth Sleepiness Scale (ESS) and overall ISI score, final visit (FV) completion, and satisfaction., Results: No relationship was noted between insomnia subtypes and AHI reduction or FV completion. In the subgroup of patients with baseline moderate/severe insomnia, patients with major impairment for SOI used their device 64 min/day longer than those with minimal impairment. Among all patients, those with baseline major impairment for SOI had a 2.3 points greater improvement in ISI from baseline to FV compared to patients with minimal impairment, while patients with baseline major impairment for SMI had a 2.0 and 3.5 points greater improvement in the ESS and ISI than those with minimal impairment. Patients with EMA and moderate/severe baseline insomnia had decreased odds of being satisfied after surgery., Conclusion: In ADHERE, nocturnal symptoms of insomnia did not limit HGNS efficacy or therapy use. Conversely, those with worse insomnia subtype impairments at baseline had improved outcomes related to adherence, sleepiness, and insomnia at the FV., Competing Interests: Reena Dhanda Patil is supported by the Cincinnati Veterans Affairs Health Care System. Maria V. Suurna: Inspire Medical—consultant, medical advisory board; Nyxoah—consulting; Medtronic—consulting, medical advisory board. Armin Steffen: Inspire Medical—consultant. The contents do not represent the views of the US Department of Veterans Affairs or those of the US government., (© 2024 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Electrochemical CO 2 reduction (CO 2 R) using heterogenized molecular catalysts usually yields 2-electron reduction products (CO, formate). Recently, it has been reported that certain preparations of immobilized cobalt phthalocyanine (CoPc) produce methanol (MeOH), a 6-electron reduction product. Here, we demonstrate the significant role of intermediate mass transport in CoPc selectivity to methanol. We first developed a simple, physically mixed, polymer (and polyfluoroalkyl, PFAS)-free preparation of CoPc on multiwalled carbon nanotubes (MWCNTs) which can be integrated onto Au electrodes using a poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) adhesion layer. After optimization of catalyst preparation and loading, methanol Faradaic efficiencies and partial current densities of 36% (±3%) and 3.8 (±0.5) mA cm -2 , respectively, are achieved in the CO 2 -saturated aqueous electrolyte. The electrolyte flow rate has a large effect. A linear flow velocity of 8.5 cm/min produces the highest MeOH selectivity, with higher flow rates increasing CO selectivity and lower flow rates increasing the hydrogen evolution reaction, suggesting that CO is an unbound intermediate. Using a continuum multiphysics model assuming CO is the intermediate, we show qualitative agreement with the optimal inlet flow rate. Polymer binders were not required to achieve a high Faradaic efficiency for methanol using CoPc and MWCNTs. We also investigated the role of formaldehyde as an intermediate and the role of strain, but definitive conclusions could not be established., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: To undertake the first ultrastructural characterization of human retinal pigment epithelial (RPE) differentiation from fetal development to adolescence., Methods: Ten fetal eyes and three eyes aged six, nine, and 17 years were examined in the temporal retina adjacent to the optic nerve head by transmission electron microscopy. The area, number, and distribution of RPE organelles were quantified and interpreted within the context of adjacent photoreceptors, Bruch's membrane, and choriocapillaris maturation., Results: Between eight to 12 weeks' gestation (WG), pseudostratified columnar epithelia with apical tight junctions differentiate to a simple cuboidal epithelium with random distribution of melanosomes and mitochondria. Between 12 to 26 WG, cells enlarge and show long apical microvilli and apicolateral junctional complexes. Coinciding with eye opening at 26 WG, melanosomes migrate apically whereas mitochondria distribute to perinuclear regions, with the first appearance of phagosomes, complex granules, and basolateral extracellular space (BES) formation. Significantly, autophagy and heterophagy, as evidenced by organelle recycling, and the gold standard of ultrastructural evidence for autophagy of double-membrane autophagosomes and mitophagosomes were evident from 32 WG, followed by basal infoldings of RPE cell membrane at 36 WG. Lipofuscin formation and deposition into the BES evident at six years increased at 17 years., Conclusions: We provide compelling ultrastructural evidence that heterophagy and autophagy begins in the third trimester of human fetal development and that deposition of cellular byproducts into the extracellular space of RPE takes place via exocytosis. Transplanted RPE cells must also demonstrate the capacity to subserve autophagic and heterophagic functions for effective disease mitigation.

Introduction: Vocal fold motion impairment (VFMI) is a known consequence after high-risk cardiac surgery. We implemented a universal laryngeal ultrasound (LUS) screening protocol for VFMI after the Norwood and aortic arch surgery. We hypothesized that LUS would accurately identify VFMI and predict postoperative aspiration., Methods: We implemented a screening algorithm with LUS for patients undergoing high-risk cardiac surgery at a tertiary care pediatric hospital. Positively screened patients underwent flexible nasolaryngoscopy (FNL). Patients with an abnormal FNL underwent a video-fluoroscopic swallow study (VFSS). Patient demographics, length of stay, and swallowing outcomes were assessed. Two-tailed chi square and Wilcoxon rank sum tests were used to assess for differences., Results: Sixty-seven patients underwent either Norwood or arch reconstruction over a 16-month period and underwent universal LUS. The average birth weight was 3.24 kg (SD 0.57). Of the 67 patients, VFMI was identified by LUS and 100% confirmed on FNL in 58.21% (n = 39/67) of patients. Aspiration and penetration on VFSS were higher in the group with VFMI as compared with those without VFMI (53.8% vs. 21.4%, p = 0.008). There was no difference in length of stay between patients who did not have a diagnosis of VFMI and those found to have VFMI (41.0 days vs 45.3 days p = 0.73)., Conclusions: Universal LUS screening for patients following high-risk cardiac surgery may lead to earlier identification of postoperative VFMI and aspiration. Recognition of VFMI through this universal screening program could lead to earlier interventions and possibly improved swallowing outcomes., Level of Evidence: 3 Laryngoscope, 134:1939-1944, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Opioids and imaging are considered low-value care for most people with low back pain. Yet around one in three people presenting to the emergency department (ED) will receive imaging, and two in three will receive an opioid. NUDG-ED aims to determine the effectiveness of two different behavioural 'nudge' interventions on low-value care for ED patients with low back pain., Methods and Analysis: NUDG-ED is a 2×2 factorial, open-label, before-after, cluster randomised controlled trial. The trial includes 8 ED sites in Sydney, Australia. Participants will be ED clinicians who manage back pain, and patients who are 18 years or over presenting to ED with musculoskeletal back pain. EDs will be randomly assigned to receive (i) patient nudges, (ii) clinician nudges, (iii) both interventions or (iv) no nudge control. The primary outcome will be the proportion of encounters in ED for musculoskeletal back pain where a person received a non-indicated lumbar imaging test, an opioid at discharge or both. We will require 2416 encounters over a 9-month study period (3-month before period and 6-month after period) to detect an absolute difference of 10% in use of low-value care due to either nudge, with 80% power, alpha set at 0.05 and assuming an intra-class correlation coefficient of 0.10, and an intraperiod correlation of 0.09. Patient-reported outcome measures will be collected in a subsample of patients (n≥456) 1 week after their initial ED visit. To estimate effects, we will use a multilevel regression model, with a random effect for cluster and patient, a fixed effect indicating the group assignment of each cluster and a fixed effect of time., Ethics and Dissemination: This study has ethical approval from Southwestern Sydney Local Health District Human Research Ethics Committee (2023/ETH00472). We will disseminate the results of this trial via media, presenting at conferences and scientific publications., Trial Registration Number: ACTRN12623001000695., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Many different animal species are susceptible to SARS-CoV-2, including a few Canidae (domestic dog and raccoon dog). So far, only experimental evidence is available concerning SARS-CoV-2 infections in red foxes ( Vulpes vulpes ). This is the first report of SARS-CoV-2 RNA detection in a sample from a red fox. The RT-qPCR-positive fox was zoo-kept together with another fox and two bears in the Swiss Canton of Zurich. Combined material from a conjunctival and nasal swab collected for canine distemper virus diagnostics tested positive for SARS-CoV-2 RNA with Ct values of 36.9 (E gene assay) and 35.7 (RdRp gene assay). The sample was analysed for SARS-CoV-2 within a research project testing residual routine diagnostic samples from different animal species submitted between spring 2020 and December 2022 to improve knowledge on SARS-CoV-2 infections within different animal species and investigate their potential role in a One Health context. Within this project, 246 samples from 153 different animals from Swiss zoos and other wild animal species all tested SARS-CoV-2 RT-qPCR and/or serologically negative so far, except for the reported fox. The source of SARS-CoV-2 in the fox is unknown. The fox disappeared within the naturally structured enclosure, and the cadaver was not found. No further control measures were undertaken.

Background and Objectives: Free open access medical education (FOAM) has become an essential tool for emergency medicine (EM) education and can be valuable to clinicians as a point-of-care resource. The development of the revised Medical Education Translational Resources Impact and Quality (rMETRIQ) tool provides a standardized means of quality assessment. Previous entries of the Society for Academic Emergency Medicine systematic online academic resource (SOAR) series have focused on renal, endocrine, and sickle cell disorders. In this iteration, we strive to identify, curate, and describe FOAM topics specific to acute gastrointestinal (GI) illnesses., Methods: We searched 389 keywords across 11 GI topics that were modified from the 2019 Model of the Clinical Practice of EM (EM Model) using the search engine Google FOAM and within the top 50 websites listed on Academic Life in Emergency Medicine's Social Media Index. The sites underwent preliminary screening to eliminate resources that were not relevant to EM or GI illnesses. Identified resources were evaluated with the rMETRIQ tool by five board-certified EM physicians who received rMETRIQ tool rater training., Results: After duplicates of the initial 39,505 resources were eliminated, 8059 remained. Primary screening resulted in a final 1202 resources. The most common categories were large bowel (18%), small bowel (13%), stomach (11%), esophagus (11%), biliary (11%), and liver (10%). Many resources covered multiple topics and subtopics. The final mean intraclass correlation coefficient among the five physicians was 0.95 (95% CI 0.92-0.98) for rMETRIQ scoring. We identified 256 sites considered "high quality" with a rMETRIQ score of 16 or higher as designated in prior reviews., Conclusions: This iteration of the SOAR review resulted in the highest number of high-quality resources compared to other SOAR reviews, with 21% of resources thus far scoring ≥ 16. A final list of high-quality resources can guide trainees, educator recommendations, and FOAM authors., Competing Interests: The authors declare no conflicts of interest., (© 2024 Society for Academic Emergency Medicine.)

Background: Older individuals are at an increased risk of delayed recovery following a traumatic injury. Measurement of muscularity and frailty at hospital admission may aid with prognostication and risk stratification., Objective: This study aimed to describe muscularity at intensive care unit (ICU) admission in patients admitted following trauma and assess the relationship between muscularity and clinical, long-term functional outcomes and frailty at ICU admission., Methods: This retrospective study utilised data from a prospective observational study investigating frailty in patients aged ≥50 years, admitted to the ICU following trauma. Patients were eligible if they had a Computed Tomography (CT) scan including the third lumbar vertebra at ICU admission. Specialist software was used to quantify CT-derived skeletal muscle cross-sectional area. Muscularity status was classified as normal or low using published sex-specific cut-points. Demographic data, frailty, clinical, and long-term functional outcomes (Glasgow Outcome Scale-Extended and EQ-5DL-5L Visual analogue scale and utility score) were extracted from the original study., Results: One hundred patients were screened; 71 patients had a CT scan on admission with 66 scans suitable for muscle assessment. Patients with low muscularity (n = 25, 38%) were older and had a higher Acute Physiology and Chronic Health Evaluation II score and lower body mass index than patients with normal muscularity. Low muscularity was associated with frailty at admission (32% vs 5%, p = 0.005) but not with long term outcomes at 6 or 12 months. As a continuous variable, lower muscle cross-sectional area was associated with a poorer outcome on the Glasgow Outcome Scale-Extended at 6 months (mean [standard deviation]: 150 [43] and 180 [44], respectively; p = 0.014), no association was observed after adjustment for age p = 0.43)., Conclusion: In a population of older adults hospitalised following trauma, low muscularity at ICU admission was prevalent. Low muscularity was associated with frailty but not long-term functional outcomes. Larger studies are warranted to better understand the relationship between muscularity and long-term functional outcomes., (Copyright © 2023 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Racial and ethnic disparities are well described in paediatric cardiac critical care outcomes. However, understanding the mechanisms behind these outcomes and implementing interventions to reduce and eliminate disparities remain a gap in the field of paediatric cardiac critical care. The Pediatric Cardiac Critical Care Consortium (PC 4 ) established the Equity, Diversity, and Inclusion (EDI) Committee in 2020 to promote an equity lens to its aim of improving paediatric cardiac critical care quality and outcomes across North America. The PC 4 EDI Committee is working to increase research, quality improvement, and programming efforts to work towards health equity. It also aims to promote health equity considerations in PC 4 research. In addition to a focus on patient outcomes and research, the committee aims to increase the inclusion of Black, Indigenous, and People of Color (BIPOC) members in the PC 4 collaborative. The following manuscript outlines the development, structure, and aims of the PC 4 EDI Committee and describes an analysis of social determinants of health in published PC 4 research.