Trends in Toddler Diet Quality in the United States: 1999 to 2018.

BACKGROUND AND OBJECTIVES: Diet quality has improved over time for US adults and youth aged ≥2 years. Trends over time and disparities in the diet quality of toddlers 12 through 23 months old have not been documented. Our objective was to investigate the direction and magnitude of toddler diet quality trends from 1999 to 2018 overall and by household socioeconomic status. METHODS: This serial cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) data was performed with 2541 toddlers from 10 NHANES cycles from 1999 to 2018. Dietary intake was measured by NHANES study staff using proxy-reported 24-hour recalls. Healthy Eating Index-Toddlers-2020 total scores (0-100 points, higher scores indicate healthier diets) and component scores were calculated from the 24-hour dietary recalls using the population ratio method. Multivariable linear regression was used to evaluate the association between time in years (measured as the midpoint of each NHANES cycle) and diet quality. RESULTS: Toddler diet quality improved significantly from 1999 to 2018 (P < .001), from 63.7 points on average in 1999-2000 to 67.7 points in 2017-2018. A significant positive linear trend in total diet quality was observed for all socioeconomic status groups (P < .05). Several dietary component scores improved, as follows: Whole Fruits (P < .001), Whole Grains (P = .016), Fatty Acids (P = .002), Refined Grains (P = .009), and Added Sugars (P < .001). Scores did not significantly change for Total Fruit, Total Vegetables, Greens and Beans, Dairy, Total Protein Foods, Seafood and Plant Proteins, Sodium, or Saturated Fats. CONCLUSIONS: From 1999 to 2018, toddler diet quality improved significantly, but mean scores still fell short of dietary guidance.

Increased TRPV4 Channel Expression Enhances and Impairs Blood Vessel Function in Hypertension.

BACKGROUND: Endothelial cell TRPV4 (transient receptor potential vanilloid 4) channels provide a control point that is pivotal in regulating blood vessel diameter by mediating the Ca2+-dependent release of endothelial-derived vasoactive factors. In hypertension, TRPV4-mediated control of vascular function is disrupted, but the underlying mechanisms and precise physiological consequences remain controversial. METHODS: Here, using a comprehensive array of methodologies, endothelial TRPV4 channel function was examined in intact mesenteric resistance arteries from normotensive Wistar-Kyoto and spontaneously hypertensive rats. RESULTS: Our results show there is a notable shift in vascular reactivity in hypertension characterized by enhanced endothelium-dependent vasodilation at low levels of TRPV4 channel activation. However, at higher levels of TRPV4 activity, this vasodilatory response is reversed, contributing to the aberrant vascular tone observed in hypertension. The change in response, from dilation to constriction, was accompanied by a shift in intracellular Ca2+ signaling modalities arising from TRPV4 activity. Oscillatory TRPV4-evoked IP3 (inositol triphosphate)-mediated Ca2+ release, which underlies dilation, decreased, while the contraction inducing sustained Ca2+ rise, arising from TRPV4-mediated Ca2+ influx, increased. Our findings also reveal that while the sensitivity of endothelial cell TRPV4 to activation was unchanged, expression of the channel is upregulated and IP3 receptors are downregulated in hypertension. CONCLUSIONS: These data highlight the intricate interplay between endothelial TRPV4 channel expression, intracellular Ca2+ signaling dynamics, and vascular reactivity. Moreover, the data support a new unifying hypothesis for the vascular impairment that accompanies hypertension. Specifically, endothelial cell TRPV4 channels play a dual role in modulating blood vessel function in hypertension.

Preoperative Factors for Success of Robotic Ureteral Reconstruction for Distal Ureteral Strictures.

Introduction: To investigate preoperative predictors of surgical success for patients undergoing robotic ureteral reconstruction (RUR) for management of distal ureteral strictures. Methods: We retrospectively reviewed our multi-institutional Collaborative of Reconstructive Robotic Ureteral Surgery database to identify all consecutive patients undergoing RUR for surgical repair of distal ureteral strictures between 04/2012 and 12/2022. Procedures included refluxing reimplant (58.5%), side to side reimplant (18.0%), ureteroureterostomy (12.7%), non-refluxing reimplant (6.3%), buccal mucosa ureteroplasty (2.8%), and appendiceal bypass ureteroplasty (1.7%). Patients were grouped according to whether they were surgically successful. Preoperative variables between both groups were compared using chi-square tests. All variables with associations of p < 0.2 underwent a binary logistic regression analysis to determine predictive variables of success for RUR (p ≤ 0.05 considered statistically significant). Results: Overall, 284 patients met inclusion criteria. Univariate analysis showed obesity (p = 0.03), smoking history (p = 0.10), abdominopelvic radiation history (p = 0.14), immunocompromised state (p = 0.12), and ureteral rest (p = 0.01) were notable preoperative factors (p < 0.2). Binary logistic regression analysis further revealed the odds of surgical success in patients with obesity was 0.32 times (CI: 0.12-0.83, p = 0.02) the odds of success for patients without obesity. The odds of surgical success in patients who underwent preoperative ureteral rest was 4.2 times (CI: 1.51-11.77, p < 0.01) the odds of success for patients who did not undergo preoperative ureteral rest. Conclusion: Preoperative factors including obesity and ureteral rest may affect surgical success of RUR for management of distal ureteral strictures.

Implementing the Infectious Diseases Society of America Antimicrobial Stewardship Core Curriculum: Survey Results and Real-World Strategies to Guide Fellowship Programs.

Background: The Infectious Diseases Society of America (IDSA) developed the Core Antimicrobial Stewardship (AS) Curriculum to meet the increasing demand for infectious diseases (ID) providers with AS expertise. Notable diversity in implementation approaches has been observed among ID fellowship programs using the curriculum. We sought to describe individual approaches and develop a curriculum implementation roadmap. Methods: We surveyed ID fellowship programs that had previously implemented the IDSA Core AS curriculum. The survey included questions regarding program characteristics, curriculum participants and presentation format, resources and barriers, and implementation strategies. Commonly reported program features were summarized in the context of the self-reported implementation strategies. Implementation guides were developed based on the most common characteristics observed. Results: Of 159 programs that had purchased the curriculum, 37 responded, and 34 (21%) were included in the analysis. The curriculum was primarily taught by AS physicians (85%) and AS pharmacists (47%). The most common conference structure was a longitudinal conference series (32%), and eLearning was the most common presentation format. Limited AS faculty time (76%) and limited first-year fellow availability (62%) were frequently reported as barriers, and dedicated AS curricular time was a resource available to most programs (67%); implementation guides were created for these 3 program features. Conclusions: Programs reported a variety of implementation barriers and resources, with several common themes emerging, allowing for the development of tailored curriculum planners for 3 commonly observed program characteristics. This work will equip fellowship programs with curriculum implementation strategies and guide future enhancements of the IDSA Core and Advanced AS curricula.

Deep Turbulence as a Novel Main Driver for Multi-Specific Toxic Algal Blooms: The Case of an Anoxic and Heavy Metal-Polluted Submarine Canyon That Harbors Toxic Dinoflagellate Resting Cysts.

Over the recent decades, an apparent worldwide rise in Harmful Algae Blooms (HABs) has been observed due to the growing exploitation of the coastal environment, the exponential growth of monitoring programs, and growing global maritime transport. HAB species like Alexandrium catenella-responsible for paralytic shellfish poisoning (PSP)-Protoceratium reticulatum, and Lingulaulax polyedra (yessotoxin producers) are a major public concern due to their negative socioeconomic impacts. The significant northward geographical expansion of A. catenella into more oceanic-influenced waters from the fjords where it is usually observed needs to be studied. Currently, their northern boundary reaches the 36°S in the Biobio region where sparse vegetative cells were recently observed in the water column. Here, we describe the environment of the Biobio submarine canyon using sediment and water column variables and propose how toxic resting cyst abundance and excystment are coupled with deep-water turbulence (10-7 Watt/kg) and intense diapycnal eddy diffusivity (10-4 m2 s-1) processes, which could trigger a mono or multi-specific harmful event. The presence of resting cysts may not constitute an imminent risk, with these resting cysts being subject to resuspension processes, but may represent a potent indicator of the adaptation of HAB species to new environments like the anoxic Biobio canyon.

On preserving anatomical detail in statistical shape analysis for clustering: focus on left atrial appendage morphology.

Introduction: Statistical shape analysis (SSA) with clustering is often used to objectively define and categorise anatomical shape variations. However, studies until now have often focused on simplified anatomical reconstructions, despite the complexity of studied anatomies. This work aims to provide insights on the anatomical detail preservation required for SSA of highly diverse and complex anatomies, with particular focus on the left atrial appendage (LAA). This anatomical region is clinically relevant as the location of almost all left atrial thrombi forming during atrial fibrillation (AF). Moreover, its highly patient-specific complex architecture makes its clinical classification especially subjective. Methods: Preliminary LAA meshes were automatically detected after robust image selection and wider left atrial segmentation. Following registration, four additional LAA mesh datasets were created as reductions of the preliminary dataset, with surface reconstruction based on reduced sample point densities. Utilising SSA model parameters determined to optimally represent the preliminary dataset, SSA model performance for the four simplified datasets was calculated. A representative simplified dataset was selected, and clustering analysis and performance were evaluated (compared to clinical labels) between the original trabeculated LAA anatomy and the representative simplification. Results: As expected, simplified anatomies have better SSA evaluation scores (compactness, specificity and generalisation), corresponding to simpler LAA shape representation. However, oversimplification of shapes may noticeably affect 3D model output due to differences in geometric correspondence. Furthermore, even minor simplification may affect LAA shape clustering, where the adjusted mutual information (AMI) score of the clustered trabeculated dataset was 0.67, in comparison to 0.12 for the simplified dataset. Discussion: This study suggests that greater anatomical preservation for complex and diverse LAA morphologies, currently neglected, may be more useful for shape categorisation via clustering analyses.

Operationalizing an adverse event detection surveillance system to support antimicrobial stewardship activities: perceptions and insights from the SHEA research network.

A surveillance system for measuring patient-level antimicrobial adverse drug events (ADE) may support stewardship activities, however, design and implementation questions remain. In this national survey, stewardship experts favored simple, laboratory-based ADE definitions although there were tensions between feasibility, ability to identify attribution without chart review, and importance of specific ADE.

Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.

BACKGROUND: Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined. OBJECTIVES: This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten. METHODS: Patients who were symptomatic of oHCM were randomized to aficamten (n = 142) or placebo (n = 140) daily for 24 weeks. Outcomes assessed included the proportion of patients with complete hemodynamic response (rest and Valsalva gradient <30 mm Hg and <50 mm Hg, respectively), relief in limiting symptoms (≥1 improvement in NYHA functional class and/or ≥10-point change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score), enhanced exercise capacity (≥1.5 mL/kg/min change in peak oxygen uptake), and ≥50% reduction in N-terminal pro-B-type natriuretic peptide. Eligibility for septal reduction therapy was also evaluated. RESULTS: At 24 weeks, patients treated with aficamten vs placebo showed significant improvement in limiting symptoms (71% vs 42%), were more likely to have complete hemodynamic response (68% vs 7%), demonstrated enhanced exercise capacity (47% vs 24%), and showed a decrease ≥50% in N-terminal pro-B-type natriuretic peptide (84% vs 8%) (P ≤ 0.002 for all). An improvement in ≥1 of these outcome measures was achieved in 97% of patients treated with aficamten (vs 59% placebo), including 23% on aficamten who achieved all 4 outcomes compared with none in placebo. Among 32 patients receiving aficamten and 29 patients receiving placebo who were eligible for septal reduction therapy, 28 (88%) from the aficamten group were no longer eligible at 24 weeks compared with 15 (52%) from the placebo group (P = 0.002). CONCLUSIONS: Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures. These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with oHCM [SEQUOIA-HCM]; NCT05186818).

DISCREPANCY BETWEEN PATIENT VERSUS PROVIDER ASSESSMENT OF ERECTION QUALITY.

OBJECTIVE: To characterize the discrepancy between patients' and providers' assessments of erection rigidity and its association with patient characteristics and penile ultrasound parameters. METHODS: Patients presenting for penile doppler ultrasound between July 2022 and October 2023 were reviewed retrospectively. After intracavernosal injection, patients and providers independently rated erection rigidity from 1 to 10 prior to ultrasound. We defined discrepancy as a difference of 2 out of 10 or greater between the two assessments. Chi-squared and Mann Whitney U tests were used for hypothesis testing. RESULTS: 65/297 (22%) of patients demonstrated a discrepancy in perceived erection quality. 58/65 (89%) of these patients rated their erections lower than their providers. There was a higher incidence of ED as the primary diagnosis in the discrepant group as compared to the concordant group (p=0.01). The discrepant group also showed a higher resistive index on penile ultrasound (p=0.04), with no difference in peak systolic velocity, end diastolic velocity, or other clinical variables between the two groups. CONCLUSION: Discrepancy in perceived erection rigidity was mainly driven by lower patient perception, although these patients had noninferior penile hemodynamics to their peers. These findings underscore the influence of subjective perception of virility on sexual function. It is critical for clinicians to identify patients with poor perception of erectile function out of proportion to physiologic abnormalities. Thoughtful counseling about treatment goals and expectations, emphasizing functional outcomes, and adjunctive treatments such as sex therapy or psychotherapy are critical to therapeutic success in this population.

Pembrolizumab-Induced Myasthenia Gravis With Myocarditis in the Setting of Metastatic Renal Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) like pembrolizumab are increasingly used for treating renal cell carcinoma (RCC), offering benefits such as enhanced specificity and activation of immunological memory. However, ICIs can lead to immune-related adverse events (irAEs), including rare but serious neurologic consequences such as myasthenia gravis (MG). We present a case of pembrolizumab-induced MG with concurrent orbital myositis and myocarditis. A 69-year-old male with a history of pT3aN1 kidney cancer presented with abdominal pain, night sweats, and weight loss. Initial imaging revealed a retroperitoneal mass and a thyroid mass, and a biopsy confirmed papillary RCC. The patient began neoadjuvant therapy with pembrolizumab and axitinib. Three weeks post-initiation, he developed dysphagia, ptosis, and proptosis, which progressed with each pembrolizumab infusion. Hospitalization was required after the third cycle due to bilateral ptosis, heart block, and elevated troponins. Despite initial steroid treatment, symptoms persisted. Diagnoses of ICI-related MG (irMG) and myocarditis were established, and treatment included cessation of pembrolizumab, high-dose steroids, IVIGs, and a pacemaker for heart block. Post-discharge, the patient showed a slight improvement in ptosis but persistent dysphagia. MG induced by ICIs is a rare but severe complication with rapid onset and progression, often presenting with bulbar involvement and a significant risk of respiratory failure. The therapeutic regimen for our patient, including high-dose methylprednisolone and IVIG, aligns with current recommendations. This case underscores the importance of recognizing cardiac irAEs like myocarditis in patients on ICIs, as early intervention can significantly affect outcomes. Despite therapeutic interventions, complete resolution of irMG symptoms is rare, and persistent sequelae are common. This case highlights the critical need for vigilant monitoring and prompt management of neurologic and cardiac irAEs in patients undergoing ICI therapy. Clinicians should maintain a high index of suspicion for MG and myocarditis to improve diagnostic accuracy and patient outcomes.

Thoracic Epidural and Analgesic Options After Failed Transversus Abdominus Plane Block With Liposomal Bupivacaine.

A 39 year-old female with a history of Roux-en-Y gastric bypass underwent emergent partial colectomy. Her postoperative analgesic management of a transversus abdominus plane block administered with a combination of bupivacaine and liposomal bupivacaine was ineffective. A bupivacaine thoracic epidural was then placed, which provided significant pain relief. This use of a bupivacaine thoracic epidural infusion following liposomal bupivacaine regional anesthesia demonstrated a case of effective analgesia without the development of local anesthetic systemic toxicity symptoms in a remote hospital setting, where certain laboratory analyses were not readily available.

Delaying post-exercise carbohydrate intake impairs next-day exercise capacity but not muscle glycogen or molecular responses.

AIM: To investigate how delayed post-exercise carbohydrate intake affects muscle glycogen, metabolic- and mitochondrial-related molecular responses, and subsequent high-intensity interval exercise (HIIE) capacity. METHODS: In a double-blind cross-over design, nine recreationally active men performed HIIE (10 × 2-min cycling, ~94% W˙peak) in the fed state, on two occasions. During 0-3 h post-HIIE, participants drank either carbohydrates ("Immediate Carbohydrate" [IC], providing 2.4 g/kg) or water ("Delayed Carbohydrate" [DC]); total carbohydrate intake over 24 h post-HIIE was matched (~7 g/kg/d). Skeletal muscle (sampled pre-HIIE, post-HIIE, +3 h, +8 h, +24 h) was analyzed for whole-muscle glycogen and mRNA content, plus signaling proteins in cytoplasmic- and nuclear-enriched fractions. After 24 h, participants repeated the HIIE protocol until failure, to test subsequent HIIE capacity; blood lactate, heart rate, and ratings of perceived effort (RPE) were measured throughout. RESULTS: Muscle glycogen concentrations, and relative changes, were similar between conditions throughout (p > 0.05). Muscle glycogen was reduced from baseline (mean ± SD mmol/kg dm; IC: 409 ± 166; DC: 352 ± 76) at post-HIIE (IC: 253 ± 96; DC: 214 ± 82), +3 h (IC: 276 ± 62; DC: 269 ± 116) and + 8 h (IC: 321 ± 56; DC: 269 ± 116), returning to near-baseline by +24 h. Several genes (PGC-1ɑ, p53) and proteins (p-ACCSer79, p-P38 MAPKThr180/Tyr182) elicited typical exercise-induced changes irrespective of condition. Delaying carbohydrate intake reduced next-day HIIE capacity (5 ± 3 intervals) and increased RPE (~2 ratings), despite similar physiological responses between conditions. CONCLUSION: Molecular responses to HIIE (performed in the fed state) were not enhanced by delayed post-exercise carbohydrate intake. Our findings support immediate post-exercise refueling if the goal is to maximize next-day HIIE capacity and recovery time is ≤24 h.

Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses.

BACKGROUND: Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear. METHODS: We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons. Proteins considered as associated with endometrial cancer risk were further tested in a two-sample Mendelian randomization (MR) analysis using summary data from the UK Biobank (n = 52,363) and the Endometrial Cancer Association Consortium (12,270 cases and 46,126 controls). FINDINGS: In the EPIC nested case-control study, IL-6 [OR per NPX (doubling of concentration) = 1.28 (95% confidence interval (CI) 1.03-1.57)], HGF [1.48 (1.06-2.07)], PIK3AP1 [1.22 (1.00-1.50)] and CLEC4G [1.52 (1.00-2.32)] were positively associated; HSD11B1 [0.67 (0.49-0.91)], SCF [0.68 (0.49-0.94)], and CCL25 [0.80 (0.65-0.99)] were inversely associated with endometrial cancer risk; all estimates had multiple comparisons adjusted P-value > 0.05. In complementary MR analysis, IL-6 [OR per inverse-rank normalized NPX = 1.19 (95% CI 1.04-1.36)] and HSD11B1 [0.91 (0.84-0.99)] were associated with endometrial cancer risk. INTERPRETATION: Altered IL-6 signalling and reduced glucocorticoid activity via HSD11B1 might play important roles in endometrial carcinogenesis. FUNDING: Funding for IIG_FULL_2021_008 was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme; Funding for INCA_15849 was obtained from Institut National du Cancer (INCa).

Operative versus conservative management for inguinal hernia: a methodology scoping review of randomized controlled trials.

INTRODUCTION: There is a lack of consensus on the management of inguinal hernia with limited symptoms. To address this issue a systematic review of existing randomized clinical trials (RCTs) was performed to critically appraise all existing data on asymptomatic hernia management, focusing on generalizability. METHODS: A scoping review to identify all RCTs comparing surgical and conservative management of patients with inguinal hernias was undertaken. Medline, Embase, Cochrane and ClinicalTrials.gov databases were searched. Data collected included study characteristics and definitions of population, intervention/comparator, and outcomes; and limitations of each study were also extracted. The quality and generalizability of included RCTs were evaluated using Cochrane's ROB-2 and the PRECIS-2 tool, respectively. RESULTS: Searches returned 661 papers; 14 full-text papers were assessed and three RCTs were identified. All RCTs included only male patients with a mean age above 55 years. All RCTs included asymptomatic patients and two included those with minimal symptoms. Different definitions for 'minimally symptomatic' were used in RCTs and none provided details of what was meant by conservative treatment. Follow-up periods varied between studies (1, 2, 3 years). All RCTs had an overall high risk of bias. According to PRECIS-2, two RCTs were classified as pragmatic, and one was equally pragmatic and explanatory. DISCUSSION: This systematic review highlights a high risk of bias but a good generalizability of the findings from the RCTs conducted on minimally symptomatic inguinal hernia patients. To improve the guidelines for the management of this group of patients, more generalizable data are needed.

Predicting peritumoral glioblastoma infiltration and subsequent recurrence using deep-learning-based analysis of multi-parametric magnetic resonance imaging.

Purpose: Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor. The standard treatment approach is surgical resection to target the enhancing tumor mass, followed by adjuvant chemoradiotherapy. However, malignant cells often extend beyond the enhancing tumor boundaries and infiltrate the peritumoral edema. Traditional supervised machine learning techniques hold potential in predicting tumor infiltration extent but are hindered by the extensive resources needed to generate expertly delineated regions of interest (ROIs) for training models on tissue most and least likely to be infiltrated. Approach: We developed a method combining expert knowledge and training-based data augmentation to automatically generate numerous training examples, enhancing the accuracy of our model for predicting tumor infiltration through predictive maps. Such maps can be used for targeted supra-total surgical resection and other therapies that might benefit from intensive yet well-targeted treatment of infiltrated tissue. We apply our method to preoperative multi-parametric magnetic resonance imaging (mpMRI) scans from a subset of 229 patients of a multi-institutional consortium (Radiomics Signatures for Precision Diagnostics) and test the model on subsequent scans with pathology-proven recurrence. Results: Leave-one-site-out cross-validation was used to train and evaluate the tumor infiltration prediction model using initial pre-surgical scans, comparing the generated prediction maps with follow-up mpMRI scans confirming recurrence through post-resection tissue analysis. Performance was measured by voxel-wised odds ratios (ORs) across six institutions: University of Pennsylvania (OR: 9.97), Ohio State University (OR: 14.03), Case Western Reserve University (OR: 8.13), New York University (OR: 16.43), Thomas Jefferson University (OR: 8.22), and Rio Hortega (OR: 19.48). Conclusions: The proposed model demonstrates that mpMRI analysis using deep learning can predict infiltration in the peri-tumoral brain region for GBM patients without needing to train a model using expert ROI drawings. Results for each institution demonstrate the model's generalizability and reproducibility.

Surgical practices in emergency umbilical hernia repair and implications for trial design.

INTRODUCTION: There is variation in the investigation, management, and surgical technique of acutely symptomatic umbilical hernias and optimal strategies remain to be established. This survey aimed to identify key variables influencing decision-making and preferred surgical techniques in emergency umbilical hernia care to help inform trial design and understand potential challenges to trial delivery. METHODS: A survey was distributed to surgeons through social media, personal contacts, and ASGBI lists. It comprised five sections: (i) performer of repair, (ii) repair preferences, (iii) important outcomes, (iv) perioperative antibiotic use, and (v) potential future trial design. RESULTS: There were 105 respondents, of which 49 (46.6%) were consultants. The median largest defect surgeons would attempt to repair with sutures alone was 2 cm (IQR 2-4 cm). In the acute setting, the most common mesh preferences are preperitoneal plane placement (n = 61, 58.1%), with synthetic non-absorbable mesh (n = 72, 68.6%), in clean (n = 41, 39.0%) or clean-contaminated (n = 52, 49.5%) wounds. Respondents believed suture repair to be associated with better short-term outcomes, and mesh repair with better long-term outcomes. Pre-/intra-operative antibiotics were very frequently given (n = 48, 45.7%) whilst post-operative antibiotics were rarely (n = 41, 39%) or very rarely (n = 28, 26.7%) given. The trial design felt to most likely influence practice is comparing mesh and suture repair, and post-operative antibiotics versus no post-operative antibiotics. Respondents indicated that to change their practice, the median difference in surgical site infection rate and recurrence rate would both need to be 5%. CONCLUSION: This survey provides insight into surgical preferences in emergency umbilical hernia management, offering guidance for the design of future trials.

Effect of Aficamten on Cardiac Structure and Function in Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM CMR Substudy.

BACKGROUND: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and left atrial dilation, which can be associated with progressive heart failure, atrial fibrillation, and stroke. Aficamten is a next-in-class cardiac myosin inhibitor that reduces outflow tract obstruction by modulating cardiac contractility, with the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events. OBJECTIVES: This study sought to investigate the effect of aficamten on cardiac remodeling compared with placebo using cardiovascular magnetic resonance (CMR) and its association with key clinical endpoints in the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) CMR substudy. METHODS: SEQUOIA-HCM was a phase 3 double-blind, placebo-controlled trial for adults with symptomatic oHCM who were randomized 1:1 to 24 weeks of aficamten (dose range: 5-20 mg) or placebo. Eligible participants were offered enrollment in the CMR substudy with studies performed at baseline and week 24. Image analysis was performed in a blinded fashion by a core laboratory. RESULTS: Of the 282 randomized patients, 57 (20%) participated in the substudy, and of those, 50 (88%) completed both baseline and week 24 CMR. Baseline characteristics of the CMR cohort were similar to the overall study population. Of these 50 patients, 21 received aficamten and 29 received placebo. Relative to placebo, patients receiving aficamten demonstrated significant reductions (Δ least-squares mean) in LV mass index (-15 g/m2; 95% CI: -25 to -6 g/m2; P = 0.001), maximal LV wall thickness (-2.1 mm; 95% CI: -3.1 to -1.1 mm; P < 0.001), left atrial volume index (-13 mL/m2; 95% CI: -19 to -7 mL/m2; P < 0.001), native T1 relaxation time (-37 ms; 95% CI: -69 to -5 ms; P = 0.026), indexed extracellular volume fraction (-3.9 g/m2; 95% CI: -7.0 to -0.9 g/m2; P = 0.014), and indexed myocyte mass (-14 g/m2; 95% CI: -23 to -4 g/m2; P = 0.004), while there were no significant changes in LV chamber volumes, LV replacement fibrosis (late gadolinium enhancement mass -0.7 g; 95% CI: -2.9 to 1.6 g; P = 0.54), or extracellular volume (0.7%; 95% CI: -2.2% to 3.6%; P = 0.61). CONCLUSIONS: The CMR substudy of SEQUOIA-HCM demonstrated that treatment with aficamten relative to placebo for 24 weeks resulted in favorable cardiac remodeling. These changes, particularly with regard to LV mass, wall thickness, and left atrial size, could potentially lead to reduced cardiovascular events including heart failure and atrial fibrillation with longer follow-up. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818).

Development of a core descriptor set for parastomal hernia repair.

AIM: Parastomal hernia repair is a poorly evidenced area, with uncertainty around the optimum management. There is considerable heterogeneity within the patient cohort, and currently there is no standardization of patient descriptors in the reporting of parastomal hernia repair. The aim of this study was to develop a core descriptor set of key patient characteristics for patients undergoing surgical repair of a parastomal hernia for reporting in all parastomal hernia research. METHOD: A longlist of descriptors was generated from a review of the existing literature. The longlist was discussed with patients with lived experience of parastomal hernia repair. Colorectal, general and hernia surgeons took part in a three-round international modified Delphi process using a nine-point Likert scale to rank the importance of descriptors. Items meeting predetermined thresholds were included in the final set and discussed and ratified at the consensus meeting. RESULTS: Seventy seven respondents completed round one, with 23 (29.8%) completing round three. Eighty six descriptors were rated across the three rounds, with 52 descriptors shortlisted. The consensus meeting ratified a final core descriptor set with 19 descriptors across eight domains: anatomy, contamination, disease, previous treatment, risk factors, symptoms, pathway and other hernia. CONCLUSION: The core descriptor set reflects characteristics that are important to surgeons when reporting on parastomal hernia repair. The use of this agreed core descriptor set may aid the reporting of future studies.