Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.

Discordant skeletal muscle gene and protein responses to exercise.

The ability of skeletal muscle to adapt to repeated contractile stimuli is one of the most intriguing aspects of physiology. The molecular bases underpinning these adaptations involve increased protein activity and/or expression, mediated by an array of pre- and post-transcriptional processes, as well as translational and post-translational control. A longstanding dogma assumes a direct relationship between exercise-induced increases in mRNA levels and subsequent changes in the abundance of the proteins they encode. Drawing on the results of recent studies, we dissect and question the common assumption of a direct relationship between changes in the skeletal muscle transcriptome and proteome induced by repeated muscle contractions (e.g., exercise).

Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).

Instant tough adhesion of polymer networks.

Generating strong rapid adhesion between hydrogels has the potential to advance the capabilities of modern medicine and surgery. Current hydrogel adhesion technologies rely primarily on liquid-based diffusion mechanisms and the formation of covalent bonds, requiring prolonged time to generate adhesion. Here, we present a simple and versatile strategy using dry chitosan polymer films to generate instant adhesion between hydrogel-hydrogel and hydrogel-elastomer surfaces. Using this approach we can achieve extremely high adhesive energies (>3,000 J/m2), which are governed by pH change and non-covalent interactions including H-bonding, Van der Waals forces, and bridging polymer entanglement. Potential examples of biomedical applications are presented, including local tissue cooling, vascular sealing, prevention of surgical adhesions, and prevention of hydrogel dehydration. We expect these findings and the simplicity of this approach to have broad implications for adhesion strategies and hydrogel design.

Heart failure with preserved ejection fraction: everything the clinician needs to know.

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognised and diagnosed in clinical practice, a trend driven by an ageing population and a rise in contributing comorbidities, such as obesity and diabetes. Representing at least half of all heart failure cases, HFpEF is recognised as a complex clinical syndrome. Its diagnosis and management are challenging due to its diverse pathophysiology, varied epidemiological patterns, and evolving diagnostic and treatment approaches. This Seminar synthesises the latest insights on HFpEF, integrating findings from recent clinical trials, epidemiological research, and the latest guideline recommendations. We delve into the definition, pathogenesis, epidemiology, diagnostic criteria, and management strategies (non-pharmacological and pharmacological) for HFpEF. We highlight ongoing clinical trials and future developments in the field. Specifically, this Seminar offers practical guidance tailored for primary care practitioners, generalists, and cardiologists who do not specialise in heart failure, simplifying the complexities in the diagnosis and management of HFpEF. We provide practical, evidence-based recommendations, emphasising the importance of addressing comorbidities and integrating the latest pharmacological treatments, such as SGLT2 inhibitors.

Resistance-only and concurrent exercise induce similar myofibrillar protein synthesis rates and associated molecular responses in moderately active men before and after training.

Aerobic and resistance exercise (RE) induce distinct molecular responses. One hypothesis is that these responses are antagonistic and unfavorable for the anabolic response to RE when concurrent exercise is performed. This thesis may also depend on the participants' training status and concurrent exercise order. We measured free-living myofibrillar protein synthesis (MyoPS) rates and associated molecular responses to resistance-only and concurrent exercise (with different exercise orders), before and after training. Moderately active men completed one of three exercise interventions (matched for age, baseline strength, body composition, and aerobic capacity): resistance-only exercise (RE, n = 8), RE plus high-intensity interval exercise (RE+HIIE, n = 8), or HIIE+RE (n = 9). Participants trained 3 days/week for 10 weeks; concurrent sessions were separated by 3 h. On the first day of Weeks 1 and 10, muscle was sampled immediately before and after, and 3 h after each exercise mode and analyzed for molecular markers of MyoPS and muscle glycogen. Additional muscle, sampled pre- and post-training, was used to determine MyoPS using orally administered deuterium oxide (D2 O). In both weeks, MyoPS rates were comparable between groups. Post-exercise changes in proteins reflective of protein synthesis were also similar between groups, though MuRF1 and MAFbx mRNA exhibited some exercise order-dependent responses. In Week 10, exercise-induced changes in MyoPS and some genes (PGC-1ɑ and MuRF1) were dampened from Week 1. Concurrent exercise (in either order) did not compromise the anabolic response to resistance-only exercise, before or after training. MyoPS rates and some molecular responses to exercise are diminished after training.

Small-world connectivity dictates collective endothelial cell signaling.

Every blood vessel is lined by a single layer of highly specialized, yet adaptable and multifunctional endothelial cells. These cells, the endothelium, control vascular contractility, hemostasis, and inflammation and regulate the exchange of oxygen, nutrients, and waste products between circulating blood and tissue. To control each function, the endothelium processes endlessly arriving requests from multiple sources using separate clusters of cells specialized to detect specific stimuli. A well-developed but poorly understood communication system operates between cells to integrate multiple lines of information and coordinate endothelial responses. Here, the nature of the communication network has been addressed using single-cell Ca2+ imaging across thousands of endothelial cells in intact blood vessels. Cell activities were cross-correlated and compared to a stochastic model to determine network connections. Highly correlated Ca2+ activities occurred in scattered cell clusters, and network communication links between them exhibited unexpectedly short path lengths. The number of connections between cells (degree distribution) followed a power-law relationship revealing a scale-free network topology. The path length and degree distribution revealed an endothelial network with a "small-world" configuration. The small-world configuration confers particularly dynamic endothelial properties including high signal-propagation speed, stability, and a high degree of synchronizability. Local activation of small clusters of cells revealed that the short path lengths and rapid signal transmission were achieved by shortcuts via connecting extensions to nonlocal cells. These findings reveal that the endothelial network design is effective for local and global efficiency in the interaction of the cells and rapid and robust communication between endothelial cells in order to efficiently control cardiovascular activity.

Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial.

BACKGROUND AND AIMS: The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy (oHCM) is not well defined. This pre-specified analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between clinical characteristics and baseline concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), and to evaluate effect of treatment with aficamten on biomarker concentrations. METHODS: Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and to evaluate whether early changes in these biomarkers relate to later changes in left ventricular outflow tract gradient (LVOT-G), other echocardiographic measures, health status, and functional capacity. RESULTS: Baseline concentration of NT-proBNP was associated with LVOT-G and measures of diastolic function, while hs-cTnI was associated with left ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was reduced by 79% (95% CI 83%-76%, P < .001) and hs-cTnI by 41% (95% CI 49%-32%, P < .001); both biomarkers reverted to baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were strongly associated with a lowering of LVOT-G, improvement in health status, and increased peak oxygen uptake. NT-proBNP reduction strongly correlated with the majority of improvements in exercise capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the 24-week change in key endpoints. CONCLUSIONS: NT-proBNP and hs-cTnI concentrations are associated with key variables in oHCM. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy.

Modern predictors and management of incidental prostate cancer at holmium enucleation of prostate.

BACKGROUND: To evaluate contemporary preoperative risk factors and subsequent postoperative management of incidental prostate cancer (iPCa) and incidental clinically significant prostate cancer (icsPCa, Grade Group [GG] ≥ 2 PCa). METHODS: A retrospective cohort of 811 men undergoing Holmium enucleation of the prostate (HoLEP) (January 2021-July 2022) were identified. Advanced preoperative testing was defined as prostate health index (PHI), prostate MRI, and/or negative preoperative biopsy. Descriptive statistics (Whitney-Mann U test, Chi-squared test) and multivariable logistic regression were performed. RESULTS: iPCa and icsPCa detection rates were 12.8% (104/811) and 4.4% (36/811), respectively. Advanced preoperative testing (406/811, 50%) was associated with younger age and higher (prostate specific antigen) PSA, prostate volume, and PSA density. On multivariable analysis, PHI ≥ 55 was associated with iPCa (OR 6.91, 95% CI 1.85-26.3, p = 0.004), and % free PSA (%fPSA) was associated with icsPCa (OR 0.83, 95% CI 0.67, 0.94, p = 0.01). GG1 disease comprised the majority of iPCa (65%, 68/104) with median 1% involvement. iPCa patients were followed with active surveillance (median follow up 9.3 months), with higher risk patients receiving prostate MRI and confirmatory biopsy. Three patients proceeded to radical prostatectomy or radiation. CONCLUSIONS: In the era of MRI and advanced biomarkers, the majority of iPCa following HoLEP is low volume GG1 suitable for active surveillance. A tentative follow-up strategy is proposed. Patients with PHI ≥ 55 or low %fPSA, even with negative prostate MRI, can consider preoperative prostate biopsy before HoLEP.

LGBTQ+ cancer: priority or lip service? A qualitative content analysis of LGBTQ+ considerations in U.S. state, jurisdiction, and tribal comprehensive cancer control plans.

The National Comprehensive Cancer Control Program, a Centers for Disease Control and Prevention funded program, supports cancer coalitions across the United States (US) in efforts to prevent and control cancer including development of comprehensive cancer control (CCC) plans. CCC plans often focus health equity within their priorities, but it is unclear to what extent lesbian, gay, bisexual, transgender, queer/questioning, plus (LGBTQ+) populations are considered in CCC plans. We qualitatively examined to what extent LGBTQ+ populations were referenced in 64 U.S. state, jurisdiction, tribes, and tribal organization CCC plans. A total of 55% of CCC plans mentioned LGBTQ+ populations, however, only one in three CCC plans mentioned any kind of LGBTQ+ inequity or LGBTQ+ specific recommendations. Even fewer plans included mention of LGBTQ+ specific resources, organizations, or citations. At the same time almost three fourths of plans conflated sex and gender throughout their CCC plans. The findings of this study highlight the lack of prioritization of LGBTQ+ populations in CCC plans broadly while highlighting exemplar plans that can serve as a roadmap to more inclusive future CCC plans. Comprehensive cancer control plans can serve as a key policy and advocacy structure to promote a focus on LGBTQ+ cancer prevention and control.

Deep learning imaging phenotype can classify metabolic syndrome and is predictive of cardiometabolic disorders.

BACKGROUND: Cardiometabolic disorders pose significant health risks globally. Metabolic syndrome, characterized by a cluster of potentially reversible metabolic abnormalities, is a known risk factor for these disorders. Early detection and intervention for individuals with metabolic abnormalities can help mitigate the risk of developing more serious cardiometabolic conditions. This study aimed to develop an image-derived phenotype (IDP) for metabolic abnormality from unenhanced abdominal computed tomography (CT) scans using deep learning. We used this IDP to classify individuals with metabolic syndrome and predict future occurrence of cardiometabolic disorders. METHODS: A multi-stage deep learning approach was used to extract the IDP from the liver region of unenhanced abdominal CT scans. In a cohort of over 2,000 individuals the IDP was used to classify individuals with metabolic syndrome. In a subset of over 1,300 individuals, the IDP was used to predict future occurrence of hypertension, type II diabetes, and fatty liver disease. RESULTS: For metabolic syndrome (MetS) classification, we compared the performance of the proposed IDP to liver attenuation and visceral adipose tissue area (VAT). The proposed IDP showed the strongest performance (AUC 0.82) compared to attenuation (AUC 0.70) and VAT (AUC 0.80). For disease prediction, we compared the performance of the IDP to baseline MetS diagnosis. The models including the IDP outperformed MetS for type II diabetes (AUCs 0.91 and 0.90) and fatty liver disease (AUCs 0.67 and 0.62) prediction and performed comparably for hypertension prediction (AUCs of 0.77). CONCLUSIONS: This study demonstrated the superior performance of a deep learning IDP compared to traditional radiomic features to classify individuals with metabolic syndrome. Additionally, the IDP outperformed the clinical definition of metabolic syndrome in predicting future morbidities. Our findings underscore the utility of data-driven imaging phenotypes as valuable tools in the assessment and management of metabolic syndrome and cardiometabolic disorders.

Real-world practice and outcomes in pilonidal surgery: Pilonidal Sinus Treatment Studying The Options (PITSTOP) cohort.

BACKGROUND: Numerous surgical approaches exist for the treatment of pilonidal disease. Current literature on treatment is of poor quality, limiting the ability to define optimal intervention. The aim of this study was to provide real-world data on current surgical practice and report patient and risk-adjusted outcomes, informing future trial design. METHODS: This UK-wide multicentre prospective cohort study, including patients (aged over 16 years) who had definitive treatment for symptomatic pilonidal disease, was conducted between May 2019 and March 2022. Patient and disease characteristics, and intervention details were analysed. Data on patient-reported outcomes, including pain, complications, treatment failure, wound issues, and quality of life, were gathered at various time points up to 6 months after surgery. Strategies were implemented to adjust for risk influencing different treatment choices and outcomes. RESULTS: Of the 667 participants consenting, 574 (86.1%) were followed up to the study end. Twelve interventions were observed. Broadly, 59.5% underwent major excisional surgery and 40.5% minimally invasive surgery. Complications occurred in 45.1% of the cohort. Those who had minimally invasive procedures had better quality of life and, after risk adjustment, less pain (score on day 1: mean difference 1.58, 95% c.i. 1.14 to 2.01), fewer complications (difference 17.5 (95% c.i. 9.1 to 25.9)%), more rapid return to normal activities (mean difference 25.9 (18.4 to 33.4) days) but a rate of higher treatment failure (difference 9.6 (95% c.i. 17.3 to 1.9)%). At study end, 25% reported an unhealed wound and 10% had not returned to normal activities. CONCLUSION: The burden after surgery for pilonidal disease is high and treatment failure is common. Minimally invasive techniques may improve outcomes at the expense of a 10% higher risk of treatment failure.

Prognostic performance of the 2023 FIGO staging schema for endometrial cancer.

OBJECTIVE: To assess the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema. METHODS: This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. Study population was 129,146 patients with stage I-IV endometrial cancer per the 2009 FIGO staging schema. Stage-shifting and overall survival (OS) were assessed according to the 2023 FIGO staging schema. RESULTS: Upstage (IA → II, 21.4 %; IB → II, 53.0 %) and downstage (IIIA→IA3, 22.2 %) occurred in both early and advanced diseases. Inter-stage prognostic performance improved in the 2023 schema with widened 5-year OS rate difference between the earliest and highest stages (68.2 % to 76.9 %). Stage IA1-IIB and IIC had distinct 5-year OS rate differences (85.8-96.1 % vs 75.4 %). The 5-year OS rate of the 2009 stage IIIA disease was 63.9 %; this was greater segregated in the 2023 schema: 88.0 %, 62.4 %, and 55.7 % for IIIA→IA3, IIIA1, and IIIA2, respectively (inter-substage rate-difference, 32.3 %). This 5-year OS rate of stage IA3 disease was comparable to the 2023 stage IB-IIB diseases (88.0 % vs 85.8-89.5 %). In the 2023 stage IIIC schema (micrometastasis rates: 29.6 % in IIIC1 and 15.6 % in IIIC2), micrometastasis and macrometastasis had the distinct 3-year OS rates in both pelvic (IIIC1-i vs IIIC1-ii, 84.9 % vs 71.1 %; rate-difference 13.8 %) and para-aortic (IIIC2-i vs IIIC2-ii, 82.9 % vs 65.2 %; rate-difference 17.7 %) nodal metastasis cases. The 5-year OS rate of the 2009 stage IVB disease was 23.4 %; this was segregated to 25.4 % for stage IVB and 19.2 % for stage IVC in the 2023 staging schema (rate-difference, 6.2 %). CONCLUSION: The 2023 FIGO endometrial cancer staging schema is a major revision from the 2009 FIGO schema. Almost doubled enriched sub-stages based on detailed anatomical metastatic site and incorporation of histological information enable more robust prognostication.

Racial and ethnic differences in early death among gynecologic malignancy.

BACKGROUND: Racial and ethnic differences in early death after cancer diagnosis have not been well studied in gynecologic malignancy. OBJECTIVE: This study aimed to assess population-level trends and characteristics of early death among patients with gynecologic malignancy based on race and ethnicity in the United States. STUDY DESIGN: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was queried to examine 461,300 patients with gynecologic malignancies from 2000 to 2020, including uterine (n=242,709), tubo-ovarian (n=119,989), cervical (n=68,768), vulvar (n=22,991), and vaginal (n=6843) cancers. Early death, defined as a mortality event within 2 months of the index cancer diagnosis, was evaluated per race and ethnicity. RESULTS: At the cohort level, early death occurred in 21,569 patients (4.7%), including 10.5%, 5.5%, 2.9%, 2.5%, and 2.4% for tubo-ovarian, vaginal, cervical, uterine, and vulvar cancers, respectively (P<.001). In a race- and ethnicity-specific analysis, non-Hispanic Black patients with tubo-ovarian cancer had the highest early death rate (14.5%). Early death racial and ethnic differences were the largest in tubo-ovarian cancer (6.4% for Asian vs 14.5% for non-Hispanic Black), followed by uterine (1.6% for Asian vs 4.9% for non-Hispanic Black) and cervical (1.8% for Hispanic vs 3.8% to non-Hispanic Black) cancers (all, P<.001). In tubo-ovarian cancer, the early death rate decreased over time by 33% in non-Hispanic Black patients from 17.4% to 11.8% (adjusted odds ratio, 0.67; 95% confidence interval, 0.53-0.85) and 23% in non-Hispanic White patients from 12.3% to 9.5% (adjusted odds ratio, 0.77; 95% confidence interval, 0.71-0.85), respectively. The early death between-group difference diminished only modestly (12.3% vs 17.4% for 2000-2002 [adjusted odds ratio for non-Hispanic White vs non-Hispanic Black, 0.54; 95% confidence interval, 0.45-0.65] and 9.5% vs 11.8% for 2018-2020 [adjusted odds ratio, 0.65; 95% confidence interval, 0.54-0.78]). CONCLUSION: Overall, approximately 5% of patients with gynecologic malignancy died within the first 2 months from cancer diagnosis, and the early death rate exceeded 10% in non-Hispanic Black individuals with tubo-ovarian cancer. Although improving early death rates is encouraging, the difference among racial and ethnic groups remains significant, calling for further evaluation.

Modification of an outcome measure to follow symptoms of children with acute otitis media.

BACKGROUND: To modify a parent-reported acute otitis media severity of symptoms scale (AOM-SOS) to ensure that it accurately reflects parental concerns. METHODS: Using qualitative interviews with parents of children with acute otitis media (AOM) (n = 24), we generated 39 candidate items for inclusion in the new version of the scale. We determined the importance of each item by enrolling 50 other parents of children with AOM. We selected 15 items with high importance and used them to create a new version of the scale. During successive rounds of cognitive interviews, 3 items were dropped. Two additional items were dropped because they were highly correlated. We evaluated the psychometric properties of the new, 10-item version (version 6.0) in 139 children with AOM. RESULTS: AOM-SOS scores correlated with functional status (r = -0.53), parent assessment of child's pain level (r = 0.69), and overall symptom severity (r = 0.41). The internal consistency of the scale, as measured by Cronbach's alpha, was 0.90. Responsiveness (standardized response mean = 1.82) and test-retest reliability (0.77) were excellent and good, respectively. CONCLUSION: Data presented here support the use of the new version of the scale as a longitudinal measure of symptom burden in clinical trials of children with AOM. IMPACT STATEMENT: The AOM-SOS scale, which now incorporates parental views, can be used to track symptom severity in future efficacy trials in young children with acute otitis media. Data is presented on the validity, reliability, and responsiveness of the AOM-SOS scale. Otitis media is the most frequent indication for antibiotic use in young children. The AOM-SOS is one of the few validated disease specific scales available for use in efficacy trials of children with acute otitis media.

The effect of sleep restriction, with or without high-intensity interval exercise, on behavioural alertness and mood state in young healthy males.

Mood state and alertness are negatively affected by sleep loss, and can be positively influenced by exercise. However, the potential mitigating effects of exercise on sleep-loss-induced changes in mood state and alertness have not been studied comprehensively. Twenty-four healthy young males were matched into one of three, 5-night sleep interventions: normal sleep (NS; total sleep time (TST) per night = 449 ± 22 min), sleep restriction (SR; TST = 230 ± 5 min), or sleep restriction and exercise (SR + EX; TST = 235 ± 5 min, plus three sessions of high-intensity interval exercise (HIIE)). Mood state was assessed using the profile of mood states (POMS) and a daily well-being questionnaire. Alertness was assessed using psychomotor vigilance testing (PVT). Following the intervention, POMS total mood disturbance scores significantly increased for both the SR and SR + EX groups, and were greater than the NS group (SR vs NS; 31.0 ± 10.7 A.U., [4.4-57.7 A.U.], p = 0.020; SR + EX vs NS; 38.6 ± 14.9 A.U., [11.1-66.1 A.U.], p = 0.004). The PVT reaction times increased in the SR (p = 0.049) and SR + EX groups (p = 0.033) and the daily well-being questionnaire revealed increased levels of fatigue in both groups (SR; p = 0.041, SR + EX; p = 0.026) during the intervention. Despite previously demonstrated physiological benefits of performing three sessions of HIIE during five nights of sleep restriction, the detriments to mood, wellness, and alertness were not mitigated by exercise in this study. Whether alternatively timed exercise sessions or other exercise protocols could promote more positive outcomes on these factors during sleep restriction requires further research.

AI-based abdominal CT measurements of orthotopic and ectopic fat predict mortality and cardiometabolic disease risk in adults.

OBJECTIVES: To evaluate the utility of CT-based abdominal fat measures for predicting the risk of death and cardiometabolic disease in an asymptomatic adult screening population. METHODS: Fully automated AI tools quantifying abdominal adipose tissue (L3 level visceral [VAT] and subcutaneous [SAT] fat area, visceral-to-subcutaneous fat ratio [VSR], VAT attenuation), muscle attenuation (L3 level), and liver attenuation were applied to non-contrast CT scans in asymptomatic adults undergoing CT colonography (CTC). Longitudinal follow-up documented subsequent deaths, cardiovascular events, and diabetes. ROC and time-to-event analyses were performed to generate AUCs and hazard ratios (HR) binned by octile. RESULTS: A total of 9223 adults (mean age, 57 years; 4071:5152 M:F) underwent screening CTC from April 2004 to December 2016. 549 patients died on follow-up (median, nine years). Fat measures outperformed BMI for predicting mortality risk-5-year AUCs for muscle attenuation, VSR, and BMI were 0.721, 0.661, and 0.499, respectively. Higher visceral, muscle, and liver fat were associated with increased mortality risk-VSR > 1.53, HR = 3.1; muscle attenuation < 15 HU, HR = 5.4; liver attenuation < 45 HU, HR = 2.3. Higher VAT area and VSR were associated with increased cardiovascular event and diabetes risk-VSR > 1.59, HR = 2.6 for cardiovascular event; VAT area > 291 cm2, HR = 6.3 for diabetes (p < 0.001). A U-shaped association was observed for SAT with a higher risk of death for very low and very high SAT. CONCLUSION: Fully automated CT-based measures of abdominal fat are predictive of mortality and cardiometabolic disease risk in asymptomatic adults and uncover trends that are not reflected in anthropomorphic measures. CLINICAL RELEVANCE STATEMENT: Fully automated CT-based measures of abdominal fat soundly outperform anthropometric measures for mortality and cardiometabolic risk prediction in asymptomatic patients. KEY POINTS: Abdominal fat depots associated with metabolic dysregulation and cardiovascular disease can be derived from abdominal CT. Fully automated AI body composition tools can measure factors associated with increased mortality and cardiometabolic risk. CT-based abdominal fat measures uncover trends in mortality and cardiometabolic risk not captured by BMI in asymptomatic outpatients.

Intrapatient Changes in CT-Based Body Composition After Initiation of Semaglutide (Glucagon-Like Peptide-1 Agonist) Therapy.

Background: The long-acting glucagon-like peptide-1 receptor agonist semaglutide is used to treat type 2 diabetes or obesity in adults. Clinical trials have observed associations of semaglutide with weight loss, improved diabetic control, and cardiovascular risk reduction. Objective: To evaluate intrapatient changes in body composition after initiation of semaglutide therapy by applying an automated suite of CT-based artificial intelligence (AI) body composition tools. Methods: This retrospective study included adult patients with semaglutide treatment who underwent abdominopelvic CT both within 5 years before and within 5 years after semaglutide initiation, between January 2016 and November 2023. An automated suite of previously validated CT-based AI body composition tools was applied to pre-semaglutide and post-semaglutide scans to quantify visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area, skeletal muscle area and attenuation, intermuscular adipose tissue (IMAT) area, liver volume and attenuation, and trabecular bone mineral density (BMD). Patients with ≥5-kg weight loss and ≥5-kg weight gain between scans were compared. Results: The study included 241 patients (mean age, 60.4±12.4 years; 151 women, 90 men). In the weight-loss group (n=67), the post-semaglutide scan, versus pre-semaglutide scan, showed decrease in VAT area (341.1 vs 309.4 cm2, p<.001), SAT area (371.4 vs 410.7 cm2, p<.001), muscle area (179.2 vs 193.0, p<.001), and liver volume (2379.0 vs 2578 HU, p=.009), and increase in liver attenuation (74.5 vs 67.6 HU, p=.03). In the weight-gain group (n=48), the post-semaglutide scan, versus pre-semaglutide scan, showed increase in VAT area (334.0 vs 312.8, p=.002), SAT area (485.8 vs 488.8 cm2, p=.01), and IMAT area (48.4 vs 37.6, p=.009), and decrease in muscle attenuation (5.9 vs 13.1, p<.001). Other comparisons were not significant (p>.05). Conclusion: Patients using semaglutide who lost versus gained weight demonstrated distinct patterns of changes in CT-based body composition measures. Those with weight loss exhibited overall favorable shifts in measures related to cardiometabolic risk. Muscle attenuation decrease in those with weight gain is consistent with decreased muscle quality. Clinical Impact: Automated CT-based AI tools provide biomarkers of body composition changes in patients using semaglutide beyond that which is evident by standard clinical measures.

A systematic review of participant descriptors reported in studies of adhesive small bowel obstruction.

AIM: Reporting of participant descriptors in studies of adhesive small bowel obstruction (ASBO) can help identify characteristics associated with favourable outcomes and allow comparison with other studies and real-world clinical populations. The aim was to identify the pattern of participant descriptors reported in studies assessing interventions for ASBO. METHOD: This systematic review was registered with PROSPERO (CRD42021281031) and reported in line with the PRISMA checklist. Systematic searches of Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were undertaken to identify studies assessing operative and non-operative interventions for adults with ASBO. Studies were dual screened for inclusion. Descriptors were categorised into conceptual domains by the research team. RESULTS: Searches identified 2648 studies, of which 73 were included. A total of 156 unique descriptors were identified. On average, studies reported 12 descriptors. The most frequently reported descriptors were sex, age, SBO aetiology, history of abdominal surgery, BMI and ASA classification. The highest number of descriptors in a single study was 34, compared to the lowest number of descriptors which was one. Pathway factors were the least frequently described domain. Overall, 37 descriptors were reported in just one study. CONCLUSION: There is a lack of consistency in participant descriptors reported in studies of SBO. Furthermore, a significant proportion of the descriptors were used infrequently. This makes it challenging to assess whether study participants are representative of the wider population. Further work is required to develop a Core Descriptor Set to standardise the reporting of patient characteristics and reduce heterogeneity between studies.

The use of core descriptors from the ENiGMA code study in recent literature: a systematic review.

AIM: The heterogeneity in data quality presented in studies regarding Crohn's anal fistula (CAF) limit extrapolation into clinical practice. The ENiGMA collaborators established a core descriptor set to standardize reporting of CAF. The aim of this work was to quantify the use of these descriptors in recent literature. METHOD: We completed a systematic review of PubMed and the Cochrane Library, extracting publications from the past 10 years specific to the clinical interventions and outcomes of CAF, and reported in line with PRISMA guidance. Each article was assessed for inclusion of ENiGMA descriptors. The median number of descriptors per publication was evaluated along with the overall frequency of each individual descriptor. Use of ENiGMA descriptors was compared between medical and procedural publications. RESULTS: Ninety publications were included. The median number of descriptors was 15 of 37; 16 descriptors were used in over half of the publications while 17 were used in fewer than a third. Descriptors were more frequently used in procedural (n = 16) than medical publications (n = 14) (p = 0.031). In procedural publications, eight descriptors were more frequently used including Faecal incontinence, Number of previous fistula interventions, Presence and severity of anorectal stenosis and Current proctitis. Medical publications were more likely to include Previous response to biological therapy and Duration and type of current course of biological therapy. CONCLUSION: With many descriptors being used infrequently and variations between medical and procedural literature, the colorectal community should assess the need for all 37 descriptors.