Effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass on body composition.

BACKGROUND: There is limited data with respect to body composition changes for laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB). The objective of this study was to analyse changes in body composition between these two procedures during the first year after bariatric surgery. METHODS: A prospective study was performed in patients undergoing bariatric surgery at two tertiary hospitals between 2017 and 2023. Body composition was assessed with dual-energy x-ray absorptiometry immediately before surgery, and at 1-, 6-, 12-, 18- and 24-months post-operatively, with a subgroup analysis performed for patients who undertook a scan at 18- and 24-months. Total weight loss (TWL), body mass index (BMI), fat mass (FM), lean body mass (LBM) and bone mineral content (BMC) parameters were compared between SG and RYGB. RESULTS: Forty-five patients were included in this series (SG n = 30, RYGB n = 15). There was a significant reduction in mean %TWL of 26.94 ± 8.86% and mean BMI of 11.12 ± 3.70 kg/m2 over 12-months. LBM accounted for 17.8% of TWL over 12-months, SG and RYGB did not differ in terms of loss of FM or LBM. For both procedures, the loss of LBM appeared to plateau at 6-months post-operatively. The only statistically significant finding between the two procedures was that RYGB resulted in an additional 0.06 kg loss compared with SG. CONCLUSION: SG and RYGB have been shown to have comparable weight loss and body composition changes in the short-to-medium term following surgery. LBM reduction was most significant in the early post-operative period across the entire cohort.

Risk Factors for Recurrence Following Arthroscopic Bankart Repair - A Systematic.

BACKGROUND: Recurrent instability remains a major source of morbidity following arthroscopic Bankart repair. Many risk factors and predictive tools have been described, but there remains a lack of consensus surrounding individual risk factors and their contribution to outcomes. PURPOSE: To systematically review the literature to identify and quantify risk factors for recurrence following arthroscopic Bankart repair. METHODS: A literature search was performed using the PubMed/Medline databases based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies were included if they evaluated risk factors for recurrent instability following arthroscopic Bankart repair. RESULTS: Overall, 111 studies were included in the analysis, including a total of 19,307 patients and 2,750 episodes of recurrent instability with 45 risk factors described. Age at operation was reported by 60 studies, with 35 finding increased risk at younger ages. Meta-analysis showed a two-fold recurrence rate of 27.0% (171/634) for patients under 20 years old compared to 13.3% (197/1485) for older patients (p<0.001). Seventeen studies completed multivariable analysis, 13 of which were significant (Odds Ratio 1.3-14.0). Glenoid bone loss was evaluated by 39 studies, with 20 finding an increased risk. Multivariable analysis in 9 studies found OR ranging from 0.7-35.1; 6 were significant. Off-track Hill-Sachs lesions were evaluated in 21 studies (13 significant), with 3 of 4 studies that conducted multivariable analysis finding a significant association with odds ratio of 2.9-8.9 of recurrence. The number of anchors used in repair was reported by 25 studies, with 4 finding increased risk with fewer anchors. Pooled analysis demonstrated a 25.0% (29/156) risk of recurrence with 2 anchors compared to 18.1% (89/491) with 3 or more anchors (p=0.06). Other frequently described risk factors included glenohumeral joint hyperlaxity (46% of studies reporting a significant association), number of preoperative dislocations (31%), contact sport participation (20%), competitive sport participation (46%), patient sex (7%), and concomitant SLAP tear (0%). CONCLUSION: Younger age, glenoid bone loss, and off-track Hill-Sachs lesions, are established risk factors for recurrence following arthroscopic Bankart repair. Other commonly reported risk factors included contact and competitive sports participation, number of fixation devices, and patient sex.

Utilizing tACS to enhance memory confidence and EEG to predict individual differences in brain stimulation efficacy.

The information transfer necessary for successful memory retrieval is believed to be mediated by theta and gamma oscillations. These oscillations have been linked to memory processes in electrophysiological studies, which were correlational in nature. In the current study, we used transcranial alternating current stimulation (tACS) to externally modulate brain oscillations to examine its direct effects on memory performance. Participants received sham, theta (4 Hz), and gamma (50 Hz) tACS over frontoparietal regions while retrieving information in a source memory paradigm. Linear regression models were used to investigate the direct effects of oscillatory non-invasive brain stimulation (NIBS) on memory accuracy and confidence. Our results indicate that both theta and gamma tACS altered memory confidence. Specifically, theta tACS seemed to lower the threshold for confidence in retrieved information, while gamma tACS appeared to alter the memory confidence bias. Furthermore, the individual differences in tACS effects could be predicted from electroencephalogram (EEG) measures recorded prior to stimulation, suggesting that EEG could be a useful tool for predicting individual variability in the efficacy of NIBS.

Simultaneous bilateral total hip arthroplasty-a survey of Irish orthopaedic surgeons' practice.

BACKGROUND: Bilateral total hip arthroplasty may be performed simultaneously (SIMTHA) or in two staged operations. AIM: To assess attitudes towards and utilization of SIMTHA in Irish orthopaedic practice, and to assess patient and surgeon factors which are associated with the management of bilateral hip arthritis. METHODS: A 16-question electronic survey (Google Forms) was distributed via email to consultant Irish orthopaedic surgeons who perform total hip arthroplasty, followed by a reminder 1 month later. A p value < 0.05 was considered significant. RESULTS: There were 53 responses from arthroplasty surgeons, with 28% reporting they never perform SIMTHA, 26% have performed ≤ 5 SIMTHA, and 46% do ≥ 1 SIMTHA per year. Amongst the 15 surgeons who do not do SIMTHA, 60% reported a preference for staged arthroplasty, 20% felt it was not feasible in their institution, and a third reported a lack of experience with SIMTHA. There was a significant association between not performing SIMTHA and years of consultant experience (p = 0.002). There were no institutional guidelines on eligibility criteria for SIMTHA. The most common time interval for staged bilateral arthroplasty was 6-12 weeks (60%). Overall, 56% of surgeons felt SIMTHA is underutilised in the Irish healthcare system; this was associated with greater SIMTHA volume (p = 0.023). CONCLUSION: Half of the Irish arthroplasty surgeons report SIMTHA is a regular aspect of their practice. Performing SIMTHA is associated with greater arthroplasty volume, more recent consultant appointments, and a perception that the operation is underutilised.

Network-based prioritization and validation of regulators of vascular smooth muscle cell proliferation in disease.

Aberrant vascular smooth muscle cell (VSMC) homeostasis and proliferation characterize vascular diseases causing heart attack and stroke. Here we elucidate molecular determinants governing VSMC proliferation by reconstructing gene regulatory networks from single-cell transcriptomics and epigenetic profiling. We detect widespread activation of enhancers at disease-relevant loci in proliferation-predisposed VSMCs. We compared gene regulatory network rewiring between injury-responsive and nonresponsive VSMCs, which suggested shared transcription factors but differing target loci between VSMC states. Through in silico perturbation analysis, we identified and prioritized previously unrecognized regulators of proliferation, including RUNX1 and TIMP1. Moreover, we showed that the pioneer transcription factor RUNX1 increased VSMC responsiveness and that TIMP1 feeds back to promote VSMC proliferation through CD74-mediated STAT3 signaling. Both RUNX1 and the TIMP1-CD74 axis were expressed in human VSMCs, showing low levels in normal arteries and increased expression in disease, suggesting clinical relevance and potential as vascular disease targets.

Defining Pseudoparalysis & Pseudoparesis - A Consensus Study.

PURPOSE: The purpose of this study was to establish consensus statements via a modified Delphi process on the definition of shoulder pseudoparalysis and pseudoparesis. METHODS: A consensus process on the definition of a diagnosis of pseudoparalysis utilizing a modified Delphi technique was conducted, and 26 shoulder/sports surgeons from 11 countries, selected based on their level of expertise in the field, participated in these consensus statements. Consensus was defined as achieving 80-89% agreement, whereas strong consensus was defined as 90-99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: Three statements regarding the diagnosis of pseudoparalysis reached strong (>89%) consensus: passive range of motion (ROM) should be unaffected, the passive range of abduction should not be considered and diagnosis should be excluded if lidocaine injection produces a substantial improvement in range of motion. Additionally, consensus (>79%) was reached that the active range of external rotation should not be considered for diagnosis, pain as a cause of restricted motion must be excluded, and that distinctions between restricted active flexion and external rotation should be made by ROM rather than tear characteristics. No consensus could be reached on statements regarding the size, number of tendons or chronicity of cuff tears. Nor was there agreement on the active range of flexion permitted or on the difference between pseudoparalysis and pseudoparesis. CONCLUSION: A modified Delphi process was utilized to establish consensus on the definition of shoulder pseudoparalysis and pseudoparesis. Unfortunately, almost half of the statements did not reach consensus, and agreement could not be reached across all domains for a unifying definition for the diagnosis of pseudoparalysis in the setting of RCTs. Furthermore, it was not agreed how or whether pseudoparalysis should be differentiated from pseudoparesis. Based on the lack of a consensus for these terms, studies should report explicitly how these terms are defined when they are used.

The diversity of social complexity in termites.

Sociality underpins major evolutionary transitions and significantly influences the structure and function of complex ecosystems. Social insects, seen as the pinnacle of sociality, have traits like obligate sterility that are considered 'master traits', used as single phenotypic measures of this complexity. However, evidence is mounting that completely aligning both phenotypic and evolutionary social complexity, and having obligate sterility central to both, is erroneous. We hypothesize that obligate and functional sterility are insufficient in explaining the diversity of phenotypic social complexity in social insects. To test this, we explore the relative importance of these sterility traits in an understudied but diverse taxon: the termites. We compile the largest termite social complexity dataset to date, using specimen and literature data. We find that although functional and obligate sterility explain a significant proportion of variance, neither trait is an adequate singular proxy for the phenotypic social complexity of termites. Further, we show both traits have only a weak association with the other social complexity traits within termites. These findings have ramifications for our general comprehension of the frameworks of phenotypic and evolutionary social complexity, and their relationship with sterility.

Genetic influence on vascular smooth muscle cell apoptosis.

Vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis play important roles in many physiological processes and pathological conditions. To identify genetic influences on VSMC behavior, we measured these traits and undertook genome-wide association studies in primary umbilical artery-derived VSMCs from >2000 individuals. Although there were no genome-wide significant associations for VSMC proliferation or migration, genetic variants at two genomic loci (7p15.3 and 7q32.3) showed highly significant associations with VSMC apoptosis (P = 1.95 × 10-13 and P = 7.47 × 10-9, respectively). The lead variant at the 7p51.3 locus was associated with increased expression of the GSDME and PALS2 genes in VSMCs. Knockdown of GSDME or PALS2 in VSMCs attenuated apoptotic cell death. A protein co-immunoprecipitation assay indicated that GSDME complexed with PALS2. PALS2 knockdown attenuated activated caspase-3 and GSDME fragmentation, whilst GSDME knockdown also reduced activated caspase-3. These findings provide new insights into the genetic regulation of VSMC apoptosis, with potential utility for therapeutic development.

Ultrafast intraoperative parathyroid hormone monitoring system: prospective, multicentre, clinical validity study.

BACKGROUND: Intraoperative parathyroid hormone (PTH) monitoring is a proven and reliable adjunct to parathyroid surgery, able to improve the outcomes and efficiency of the diagnostic and therapeutic pathway for patients with primary hyperparathyroidism. This study evaluated the innovative, compact, fully automated NBCL CONNECT Analyzer, which can measure whole-blood PTH in 5 min. METHODS: A prospective multicentre study was conducted in stages: results reviews, recommendations, and implementation of improvements to the mechanical design, components of cartridges, calibration, and sampling protocols. Patients undergoing parathyroidectomy had PTH levels measured on the Analyzer and main laboratory platforms, either Roche or Abbott. The Miami criterion of a 50% drop in PTH concentration was used to define biochemical cure during surgery, and normal postoperative calcium level as cure of primary hyperparathyroidism. Measurements on the Analyzer were done by laboratory staff in London and nurses in Stuttgart. The Pearson coefficient (R) and Wilcoxon test were used for statistical analysis. RESULTS: Some 234 patients (55 male, 179 female) with a median age of 58.5 (age full range 15-88) years underwent parathyroidectomy (195 minimally invasive, 38 bilateral neck exploration, 1 thoracoscopic; 12 conversions) for primary hyperparathyroidism between November 2021 and July 2022. Primary hyperparathyroidism was cured in 225 patients (96.2%). The sensitivity, specificity, and overall accuracy of the Analyzer assay in predicting biochemical cure were 83.9, 100, and 84.8% in phase 1; 91.2, 100, and 91.3% in phase 2; and 98.6, 100, and 98.6% in phase 3. There were no false-positive results (positive predictive value 100%). Correlations between Analyzer measurements and those obtained using the Roche device were very strong (R = 0.98, P < 0.001 in phase 1; R = 0.92, P < 0.001 in phase 2; R = 0.94, P < 0.001 in phase 3), and correlations for Analyzer readings versus those from the Abbott platform were strong (R = 0.82, P < 0.001; R = 0.89, P < 0.001; R = 0.91, P < 0.001). The Analyzer showed continued good mechanical performance, with stable and repeatable operations (calibrations, quality controls). Introducing a stricter sampling protocol and improvements in the clot-detecting system led to a decrease in the number of clotted samples and false-negative results. Outcomes were not affected by measurements performed either by nurses or laboratory staff. CONCLUSION: Intraoperative PTH monitoring during parathyroid surgery can be done accurately, simply, and quickly in whole blood using the Analyzer.

Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease.

BACKGROUND: Placebo-controlled evidence from ORBITA-2 (Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina-2) found that percutaneous coronary intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many patients. The reason for this was unclear. OBJECTIVES: This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, noninvasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI. METHODS: Prerandomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the World Health Organization Rose angina questionnaire (Rose). Disease severity was assessed using quantitative coronary angiography, stress echocardiography, fractional flow reserve, and instantaneous wave-free ratio. Bayesian ordinal regression was used. RESULTS: At prerandomization, the median number of daily angina episodes was 0.8 (Q1-Q3: 0.4-1.6), 64% had Rose angina, quantitative coronary angiography diameter stenosis was 61% (Q1-Q3: 49%-74%), stress echocardiography score was 1.0 (Q1-Q3: 0.0-2.7), fractional flow reserve was 0.63 (Q1-Q3: 0.49-0.75), and instantaneous wave-free ratio was 0.78 (Q1-Q3: 0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with quantitative coronary angiography ordinal correlation coefficient: 0.06 (95% credible interval [CrI]: 0.00-0.08); stress echocardiography: 0.09 (95% CrI: 0.02-0.10); fractional flow reserve: 0.04 (95% CrI: -0.03 to 0.07); and instantaneous wave-free ratio: 0.04 (95% CrI: -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR: 1.9; 95% CrI: 1.6-2.1; probability of interaction [PrInteraction] = 99.9%; and OR: 1.8; 95% CrI: 1.6-2.1; PrInteraction = 99.9%, respectively). CONCLUSIONS: Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI.

Posterior Shoulder Instability, Part I-Diagnosis, Nonoperative Management, and Labral Repair for Posterior Shoulder Instability-An International Expert Delphi Consensus Statement.

PURPOSE: To establish consensus statements on the diagnosis, nonoperative management, and labral repair for posterior shoulder instability. METHODS: A consensus process on the treatment of posterior shoulder instability was conducted, with 71 shoulder/sports surgeons from 12 countries participating on the basis of their level of expertise in the field. Experts were assigned to 1 of 6 working groups defined by specific subtopics within posterior shoulder instability. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: Unanimous agreement was reached on the indications for nonoperative management and labral repair, which include whether patients had primary or recurrent instability, with symptoms/functional limitations, and whether there was other underlying pathology, or patient's preference to avoid or delay surgery. In addition, there was unanimous agreement that recurrence rates can be diminished by attention to detail, appropriate indication and assessment of risk factors, recognition of abnormalities in glenohumeral morphology, careful capsulolabral debridement and reattachment, small anchors with inferior placement and multiple fixation points that create a bumper with the labrum, treatment of concomitant pathologies, and a well-defined rehabilitation protocol with strict postoperative immobilization. CONCLUSIONS: The study group achieved strong or unanimous consensus on 63% of statements related to the diagnosis, nonoperative treatment, and labrum repair for posterior shoulder instability. The statements that achieved unanimous consensus were the relative indications for nonoperative management, and the relative indications for labral repair, as well as the steps to minimize complications for labral repair. There was no consensus on whether an arthrogram is needed when performing advanced imaging, the role of corticosteroids/orthobiologics in nonoperative management, whether a posteroinferior portal is required. LEVEL OF EVIDENCE: Level V, expert opinion.

Posterior Shoulder Instability Part II - Glenoid Bone-Grafting, Glenoid Osteotomy, and Rehabilitation/Return to Play - An International Expert Delphi Consensus Statement.

PURPOSE: The purpose of this study was to establish consensus statements on glenoid bone-grafting, glenoid osteotomy, rehabilitation, return to play, and follow-up for posterior shoulder instability. METHODS: A consensus process on the treatment of posterior shoulder instability was conducted, with 71 shoulder/sports surgeons from 12 countries participating based on their level of expertise in the field. Experts were assigned to one of 6 working groups defined by specific subtopics within posterior shoulder instability. Consensus was defined as achieving 80-89% agreement, whereas strong consensus was defined as 90-99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: All of the statements relating to rehabilitation, return to play, and follow-up achieved consensus. There was unanimous consensus that the following criteria should be considered: restoration of strength, range of motion, proprioception, and sport-specific skills, with a lack of symptoms. There is no minimum time point required to return to play. Collision athletes and military athletes may take longer to return because of their higher risk for recurrent instability, and more caution should be exercised in clearing them to return to play, with elite athletes potentially having different considerations in returning to play. The relative indications for revision surgery are symptomatic apprehension, multiple recurrent instability episodes, further intra-articular pathologies, hardware failure, and pain. CONCLUSION: The study group achieved strong or unanimous consensus on 59% of statements. Unanimous consensus was reached regarding the criteria for return to play, collision/elite athletes having different considerations in return to play, indications for revision surgery, and imaging only required as routine for those with glenoid bone-grafting/osteotomies at subsequent follow-ups. There was no consensus on optimal fixation method for a glenoid bone-block, the relative indications for glenoid osteotomy, whether fluoroscopy is required or if the labrum should be concomitantly repaired. LEVEL OF EVIDENCE: Level V Expert Opinion.

Identification of Faba bean genetic loci associated with quantitative resistance to the fungus Botrytis fabae, causal agent of chocolate spot.

Introduction: Chocolate spot, caused by the ascomycete fungus Botrytis fabae, is a devastating foliar disease and a major constraint on the quality and yield of faba beans (Vicia faba). The use of fungicides is the primary strategy for controlling the disease. However, high levels of partial genetic resistance have been identified and can be exploited to mitigate the disease. Methods: The partially resistant V. faba cultivar Maris Bead and susceptible Egyptian accession ig70726 were crossed, and a genetic mapping population of 184 individuals was genotyped in the F2 generation and screened for resistance to B. fabae infection in the F3, F5, and F6 generations in a series of field experiments. A high-density linkage map of V. faba containing 3897 DArT markers spanning 1713.7 cM was constructed. Results: Multiple candidate quantitative trait loci (QTLs) in 11 separate regions of the V. faba genome were identified; some on chromosomes 2, 3, and 6 overlapped with loci previously linked to resistance to Ascochyta leaf and pod blight caused by the necrotrophic fungus Ascochyta fabae. A transcriptomics experiment was conducted at 18 h post-inoculation in seedlings of both parents of the mapping population, identifying several differentially expressed transcripts potentially involved in early stage defence against B. fabae, including cell-wall associated protein kinases, NLR genes, and genes involved in metabolism and response to reactive oxygen species. Discussion: This study identified several novel candidate QTLs in the V. faba genome that contribute to partial resistance to chocolate spot, but differences between growing seasons highlighted the importance of multi-year phenotyping experiments when searching for candidate QTLs for partial resistance.

Editorial Commentary: Latarjet for Anterior Shoulder Instability Literature Shows Limited Reporting of Outcomes in Female Patients: Female Patients Show Similar Outcomes but Greater Rate of Emergency Department Visits and Possible Greater of Complications.

It has been reported that use of the Latarjet procedure for anterior shoulder instability increased 250% from 2008 to 2019. With this increase in use, it is imperative to minimize complications. At present, most literature focuses on male patients, with scant evidence regarding female patients. Outcomes are similar when female with male patients are compared, but female patients have greater postoperative visits to the emergency department than male patients, which requires specific attention during the postoperative period. In addition, the literature reporting complications in female versus male patients after Latarjet is conflicting; some studies show similar rates of complications, whereas other studies show greater rates of adverse events in female patients. Previous consensus statements recommended (1) careful dissection; (2) identification of the musculocutaneous and axillary nerves; (3) prevention of overlateralization of the graft; (4) the use of tranexamic acid to reduce blood loss; (5) accurate screw placement; and (6) careful preparation of the glenoid neck and coracoid to reduce rates of nonunion or delayed union.

How useful are genomic data for predicting maladaptation to future climate?

Methods using genomic information to forecast potential population maladaptation to climate change or new environments are becoming increasingly common, yet the lack of model validation poses serious hurdles toward their incorporation into management and policy. Here, we compare the validation of maladaptation estimates derived from two methods-Gradient Forests (GFoffset) and the risk of non-adaptedness (RONA)-using exome capture pool-seq data from 35 to 39 populations across three conifer taxa: two Douglas-fir varieties and jack pine. We evaluate sensitivity of these algorithms to the source of input loci (markers selected from genotype-environment associations [GEA] or those selected at random). We validate these methods against 2- and 52-year growth and mortality measured in independent transplant experiments. Overall, we find that both methods often better predict transplant performance than climatic or geographic distances. We also find that GFoffset and RONA models are surprisingly not improved using GEA candidates. Even with promising validation results, variation in model projections to future climates makes it difficult to identify the most maladapted populations using either method. Our work advances understanding of the sensitivity and applicability of these approaches, and we discuss recommendations for their future use.

Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomised, placebo-controlled trial.

BACKGROUND: The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. METHODS: ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. FINDINGS: Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. INTERPRETATION: ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. FUNDING: Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

DrivR-Base: a feature extraction toolkit for variant effect prediction model construction.

MOTIVATION: Recent advancements in sequencing technologies have led to the discovery of numerous variants in the human genome. However, understanding their precise roles in diseases remains challenging due to their complex functional mechanisms. Various methodologies have emerged to predict the pathogenic significance of these genetic variants. Typically, these methods employ an integrative approach, leveraging diverse data sources that provide important insights into genomic function. Despite the abundance of publicly available data sources and databases, the process of navigating, extracting, and pre-processing features for machine learning models can be highly challenging and time-consuming. Furthermore, researchers often invest substantial effort in feature extraction, only to later discover that these features lack informativeness. RESULTS: In this article, we introduce DrivR-Base, an innovative resource that efficiently extracts and integrates molecular information (features) related to single nucleotide variants. These features encompass information about the genomic positions and the associated protein positions of a variant. They are derived from a wide array of databases and tools, including structural properties obtained from AlphaFold, regulatory information sourced from ENCODE, and predicted variant consequences from Variant Effect Predictor. DrivR-Base is easily deployable via a Docker container to ensure reproducibility and ease of access across diverse computational environments. The resulting features can be used as input for machine learning models designed to predict the pathogenic impact of human genome variants in disease. Moreover, these feature sets have applications beyond this, including haploinsufficiency prediction and the development of drug repurposing tools. We describe the resource's development, practical applications, and potential for future expansion and enhancement. AVAILABILITY AND IMPLEMENTATION: DrivR-Base source code is available at https://github.com/amyfrancis97/DrivR-Base.

Early outcomes after post-cardiotomy extracorporeal membrane oxygenation in paediatric patients: a contemporary, binational cohort study.

OBJECTIVES: The aim of this study was to assess the early outcomes and risk factors of paediatric patients requiring extracorporeal membrane oxygenation after cardiac surgery (post-cardiotomy). METHODS: Retrospective binational cohort study from the Australia and New Zealand Congenital Outcomes Registry for Surgery database. All patients younger than 18 years of age who underwent a paediatric cardiac surgical procedure from 1 January 2013 to 31 December 2021 and required post-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) in the same hospital admission were included in the study. RESULTS: Of the 12 290 patients included in the study, 376 patients required post-cardiotomy ECMO (3%). Amongst these patients, hospital mortality was 35.6% and two-thirds of patients experienced a major complication. Hypoplastic left heart syndrome was the most common diagnosis (17%). The Norwood procedure and modified Blalock-Taussig shunts had the highest incidence of requiring PC-ECMO (odds ratio of 10 and 6.8 respectively). Predictors of hospital mortality after PC-ECMO included single-ventricle physiology, intracranial haemorrhage and chylothorax. CONCLUSIONS: In the current era, one-third of patients who required PC-ECMO after paediatric cardiac surgery in Australia and New Zealand did not survive to hospital discharge. The Norwood procedure and isolated modified Blalock-Taussig shunt had the highest incidence of requiring PC-ECMO. Patients undergoing the Norwood procedure had the highest mortality (48%). Two-thirds of patients on PC-ECMO developed a major complication.