Systematic Reporting of Eosinophils in Transbronchial Biopsies After Lung Transplantation Defines a Distinct Inflammatory Response.

BACKGROUND: Descriptions of eosinophils in transbronchial biopsy (TBBx) pathology reports after lung transplantation (LTx) are associated with poor long-term outcomes. The absence of routine reporting and standardization precludes accurate assessment of this histologic predictor. A systematic reporting scheme for the presence of TBBx eosinophils after LTx was implemented. This report aims to assess this scheme by describing the presence, pattern, and gradation of TBBx eosinophils and clinical associations. METHODS: A prospective cross-sectional study of all TBBx reports was performed including all patients presenting for a surveillance or diagnostic TBBx between January 2020 and June 2023. Each TBBx was systematically reported in a blinded manner. Mixed-effects logistic regression was performed to measure the association between concurrent clinical and histologic features, and the presence of TBBx eosinophils. RESULTS: A total of 410 TBBx reports from 201 patients were systematically reported. In 43.8% recipients, any TBBx eosinophils were detected and in 17.1% recipients, higher-grade eosinophils (≥3 per high power field) were present. Adjusted analysis showed that retransplantation, A- and B-grade cellular rejection, positive bronchoalveolar lavage (BAL) bacterial microbiology, and elevated blood eosinophil count were independently associated with the presence of any TBBx eosinophils. Diagnostic "for-cause" procedures were independently associated with higher quantities of TBBx eosinophils. CONCLUSIONS: Systematic reporting demonstrates that TBBx eosinophils are a distinct inflammatory response associated with rejection, infection, and peripheral eosinophilia. Although these findings require multicenter external validation, standardized reporting for TBBx eosinophils may assist in identifying recipients at risk of poor outcomes and provides a platform for mechanistic research into their role after lung transplantation.

Impact of Social Determinants of Health on Predictive Models for Outcomes After Congenital Heart Surgery.

BACKGROUND: Despite documented associations between social determinants of health and outcomes post-congenital heart surgery, clinical risk models typically exclude these factors. OBJECTIVES: The study sought to characterize associations between social determinants and operative and longitudinal mortality as well as assess impacts on risk model performance. METHODS: Demographic and clinical data were obtained for all congenital heart surgeries (2006-2021) from locally held Congenital Heart Surgery Collaborative for Longitudinal Outcomes and Utilization of Resources Society of Thoracic Surgeons Congenital Heart Surgery Database data. Neighborhood-level American Community Survey and composite sociodemographic measures were linked by zip code. Model prediction, discrimination, and impact on quality assessment were assessed before and after inclusion of social determinants in models based on the 2020 Society of Thoracic Surgeons Congenital Heart Surgery Database Mortality Risk Model. RESULTS: Of 14,173 total index operations across New York State, 12,321 cases, representing 10,271 patients at 8 centers, had zip codes for linkage. A total of 327 (2.7%) patients died in the hospital or before 30 days, and 314 children died by December 31, 2021 (total n = 641; 6.2%). Multiple measures of social determinants of health explained as much or more variability in operative and longitudinal mortality than clinical comorbidities or prior cardiac surgery. Inclusion of social determinants minimally improved models' predictive performance (operative: 0.834-0.844; longitudinal 0.808-0.811), but significantly improved model discrimination; 10.0% more survivors and 4.8% more mortalities were appropriately risk classified with inclusion. Wide variation in reclassification was observed by site, resulting in changes in the center performance classification category for 2 of 8 centers. CONCLUSIONS: Although indiscriminate inclusion of social determinants in clinical risk modeling can conceal inequities, thoughtful consideration can help centers understand their performance across populations and guide efforts to improve health equity.

Reoperations in Adolescents and Adults after Prior Arterial Switch Operation: STS Congenital Database Analysis.

BACKGROUND: Arterial switch operation (ASO) has supplanted physiologic repairs for transposition of the great arteries and related anomalies. As survival rates have increased, so has the potential need for cardiac reoperations to address ASO-related complications arising later in life. METHODS: The STS-CHSD (2010-2021) was reviewed to assess prevalence and types of cardiac reoperations among patients aged ≥10 years with prior ASO for TGA or DORV/TGA-type. A hierarchical stratification designating 13 Procedure Categories was established a priori by investigators. Each eligible surgical hospitalization was assigned to the single highest applicable hierarchical category. Outcomes were compared across Procedure Categories, excluding hospitalizations limited to pacemaker-only and/or mechanical circulatory support-only procedures. Variation over the study period in relative proportions of Left Heart vs Non-Left Heart Procedure Category encounters was assessed. RESULTS: There were 698 cardiac surgical hospitalizations among patients aged 10-35 years at 100 centers. The most common Left Heart Procedure Categories were Aortic Valve procedures (n=146), Aortic Root procedures (n=117), and Coronary Artery procedures (n=40). Of 619 hospitalizations eligible for outcomes analysis, Major Complications occurred in 11% (67/619). Discharge mortality was 2.3% (14/619). Year-by-year analysis of surgical hospitalizations reveals substantial growth in numbers for the aggregate of all Procedure Categories. Growth in relative proportions of Left Heart vs Non-Left Heart Procedures was significant, p=0.0029 (Cochran-Armitage trend test). CONCLUSIONS: This largest multicenter study of post-ASO reoperations beyond early childhood documents year-over-year growth in total reoperations. Recently, left heart procedures had the highest rate of rise. These observations have implications for counseling, surveillance, and management.

Risk of Cardiac Reoperation: An Analysis of The STS Congenital Heart Surgery Database.

BACKGROUND: The increasing number of congenital heart disease patients undergoing reoperative cardiac surgery presents critical and growing challenges. Our objective was to evaluate the association between number of prior cardiopulmonary bypass operations and operative mortality and morbidity in a national cohort. METHODS: The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) was reviewed for index cardiac operations on cardiopulmonary bypass during 2016-2021. Infants and patients with functionally univentricular physiology were excluded. Multivariable logistic regression adjusted for covariates in the STS-CHSD Mortality Risk Model, STAT Mortality Category, and institutional volume. RESULTS: Of 50,625 eligible operations, 22,100 (44%) were performed on patients with ≥1 prior cardiopulmonary bypass operation. Most common diagnoses were Tetralogy of Fallot (4,340/22,100 [19.6%]), pulmonary atresia/ventricular septal defect (1,334/22,100 [6.0%]), and aortic stenosis (966/22,100 [4.4%]). Operative mortality correlated with number of prior cardiopulmonary bypass operations, 157/28,525 (0.6%) for zero, 127/13,488 (0.9%) for one, 81/5,664 (1.4%) for two, 61/2,039 (3.0%) for three, 35/623 (5.6%) for four, 10/207 (4.8%) for five, and 5/79 (6.3%) for ≥6 (p<0.001). On multivariable analysis, patients with ≥3 prior cardiopulmonary bypass operations had higher risk of operative mortality (OR 2.31, p<0.001) and major morbidity (OR 1.60, p<0.001). Annual institutional volume and age were not associated with either outcome. CONCLUSIONS: Three or more prior cardiopulmonary bypass operations was an independent risk factor for operative mortality/morbidity, even after controlling for risk factors and institutional volume. Future research is needed to identify modifiable factors to optimize outcomes, particularly for those with ≥3 prior cardiopulmonary bypass operations.

Renal autotransplantation: association between preoperative disease duration and surgical outcomes.

OBJECTIVE: To determine whether early vs. delayed autotransplantation are associated with adverse outcomes in patients undergoing renal autotransplantation. METHODS: Patients who underwent renal autotransplantation from June 2012 to September 2022 were divided into two groups based on timing of autotransplant in relation to initial intervention or diagnosis (early cohort: ≤1-year; delayed cohort: >1-year). Primary outcomes were perioperative complications, aborted surgery, renal function (glomerular filtration rate [GFR]), and postoperative complications at most recent follow-up. RESULTS: Autotransplantation patients (N=72) were predominantly female (68%) and White (54%), with a median age of 49 years. 90% of patients had undergone previous interventions, including stenting (40%) and nephrostomy tubes (49%), primarily for obstruction (64%). Early vs. delayed cohorts had median preoperative disease durations of 143 (IQR 83-222) vs. 673 days (IQR 529-1,703, p<0.001), with similar median follow-up times (879 vs. 818 days, p=0.8). Groups were similar in demographics and comorbidities. There were no significant differences in rates of aborted surgery (15% vs. 4.2%, p=0.3), perioperative complications (15% vs. 17%, p>0.9), long-term complications (49% vs. 48%, p>0.9), or changes in GFR (median change +3 vs. +4, p=0.7). Outcomes were comparable across preoperative disease durations ranging from 6 to 24 months. These findings were confirmed following adjustments for sex, body mass index, American Society of Anesthesiologists classification, race, preoperative creatinine levels, laterality, gastroesophageal reflux disease, diabetes, hypertension, nephrolithiasis, hyperlipidemia, history of colon surgery, urologic surgery, abdominal surgery, and prior interventions in separate logistic models. CONCLUSIONS: Disease duration before autotransplantation does not influence outcomes, offering reassurance for clinical decision-making in complex cases.

Biomechanical Analysis of Age-Dependent Changes in Fontan Power Loss.

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits.

Ureteral avulsion after ureteroscopy treated with renal auto-transplantation.

Ureteral avulsion can be secondary to blunt or penetrating trauma, or can emerge as a surgical complication. Popularization of minimally invasive interventions has significantly decreased ureteral injuries, ranging from 0% to 28% and varying from minor mucosal injury to perforation, and most catastrophically, avulsion. We present a case of complete ureteral avulsion that was not initially appreciated after undergoing ureteroscopy for stone extraction. Eventual recognition of this injury was managed successfully with a subsequent laparoscopically nephrectomy and renal auto-transplantation preserving renal function.

Evaluating registry-based trial economics: Results from the STRESS clinical trial.

Background: Registry-based trials have the potential to reduce randomized clinical trial (RCT) costs. However, observed cost differences also may be achieved through pragmatic trial designs. A systematic comparison of trial costs across different designs has not been previously performed. Methods: We conducted a study to compare the current Steroids to Reduce Systemic inflammation after infant heart surgery (STRESS) registry-based RCT vs. two established designs: pragmatic RCT and explanatory RCT. The primary outcome was total RCT design costs. Secondary outcomes included: RCT duration and personnel hours. Costs were estimated using the Duke Clinical Research Institute's pricing model. Results: The Registry-Based RCT estimated duration was 31.9 weeks greater than the other designs (259.5 vs. 227.6 weeks). This delay was caused by the Registry-Based design's periodic data harvesting that delayed site closing and statistical reporting. Total personnel hours were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design (52,488 vs 29,763 vs. 24,480 h, respectively). Total costs were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design ($10,140,263 vs. $4,164,863 vs. $3,268,504, respectively). Thus, Registry-Based total costs were 32 % of the Explanatory and 78 % of the Pragmatic design. Conclusion: Total costs for the STRESS RCT with a registry-based design were less than those for a pragmatic design and much less than an explanatory design. Cost savings reflect design elements and leveraging of registry resources to improve cost efficiency, but delays to trial completion should be considered.

Outcomes of the Kawashima: A Society of Thoracic Surgeons Congenital Heart Surgery Database Analysis.

BACKGROUND: We aimed to evaluate the effect of age at operation on postoperative outcomes in children undergoing a Kawashima operation. METHODS: The Society of Thoracic Surgeons Congenital Heart Surgery Database was queried for Kawashima procedures from January 1, 2014, to June 30, 2020. Patients were stratified by age at operation in months: 0 to <4, 4 to <8, 8 to <12, and >12. Subsequently, outcomes for those in whom the Kawashima was not the index operation and for those undergoing hepatic vein incorporation (Fontan completion or hepatic vein-to-azygos vein connection) were evaluated. RESULTS: We identified 253 patients who underwent a Kawashima operation (median age, 8.6 months; median weight, 7.4 kg): 12 (4.7%), 0 to <4 months; 96 (37.9%), 4 to <8 months; 81 (32.0%), 8 to <12 months; and 64 (25.3%), >12 months. Operative mortality was 0.8% (n = 2), with major morbidity or mortality in 17.4% (n = 44), neither different across age groups. Patients <4 months had a longer postoperative length of stay (12.5 vs 9.3 days; P = .03). The Kawashima was not the index operation of the hospital admission in 15 (5.9%); these patients were younger (6.0 vs 8.4 months; P = .05) and had more preoperative risk factors (13/15 [92.9%] vs 126/238 [52.9%]; P < .01). We identified 173 patients undergoing subsequent hepatic vein incorporation (median age, 3.9 years; median weight, 15.0 kg) with operative mortality in 6 (3.5%) and major morbidity or mortality in 30 (17.3%). CONCLUSIONS: The Kawashima is typically performed between 4 and 12 months with low mortality. Morbidity and mortality were not affected by age. Hepatic vein incorporations may be higher risk than in traditional Fontan procedures, and ways to mitigate this should be sought.

Treatment of Postoperative Neck Dissection Cervical Lymphocele With Percutaneous Bleomycin Sclerotherapy.

Lymphatic leak after lymph node dissection is a rare but well-known surgical complication that is often treated with conservative management and ultimately reoperation. The purpose of this report is to offer an alternative treatment for chyle leak that avoids hospitalization and subsequent surgery. Sclerotherapy has been used to treat lymphatic leaks in the past and has been shown to be safe and effective. This report presents a patient with a known cervical lymphocele who was followed through multiple sclerotherapy appointments until resolution of the lymphocele.

Reimagining Ambulatory Care in Urology: Conversion of the Urology Clinic into a Procedure Center Improves Patient's Experience.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic made it necessary to practice social distancing and limited in-person encounters in health care. These restrictions created alternative opportunities to enhance patient access to care in the ambulatory setting. We hypothesized that by transforming clinics into centers that prioritize procedures and transitioning ambulatory appointments to telehealth, we could establish a secure, streamlined, and productive method for providing patient care. Methods: Clinic templates were restructured to allow the use of the physical space to perform procedure-based clinics exclusively, while switching to virtual telemedicine for all nonprocedural encounters. Staff members were given specific roles to support one of the patient care modalities for a given day (Procedures vs. Telehealth). Performance and patient satisfaction metrics were collected between two periods of time defined as P1 (February-June 2019) and P2 Post-COVID (February-June 2020) and compared. These served as proxies of periods when the clinic workflow and templates were structured in the traditional versus the emerging way. Statistical analysis was performed using bivariate analyses. Results: The percentage of procedures performed among all in-person visits were higher in P2 compared to P1 (45% vs. 29%, p < 0.001). Although total charges and relative value units were lower in P2, the overall revenue generated was higher compared to P1 ($4,597,846 vs. $4,517,427$, respectively). This increase in revenue was mainly driven by the higher relative income generated by procedures. Patient experience, reflected through patient-reported outcomes, was more favorable in P2 where patients seemed more likely to "Recommend this provider office" (90% vs. 85.7%, p = 0.01), report improved "Access overall" (56% vs. 49%, p = 0.02), and felt they were "Moving through your visit overall" (59% vs. 51%, p = 0.007). Conclusions: Our data suggest that reorganizing urology clinics into a space that is centered around outpatient procedures can represent a model that improves the patient's access to care and clinical experience, while simultaneously improving operational financial strength. This efficient care model could be considered for many practice settings and drive high-value outpatient care.

Contemporary Applications and Outcomes of Pulmonary Artery Banding: An Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database.

BACKGROUND: Pulmonary artery banding (PAB) in isolation or combined with a congenital cardiac surgical procedure is common and has important mortality. We aimed to determine patient characteristics, clinical outcomes, variation in clinical outcomes by diagnoses, and center variation in PAB use. METHODS: Using The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD), this study evaluated outcomes of patients undergoing PAB across diagnoses, participating centers, and additional procedures. Patients were identified by procedure and diagnosis codes from 2016 to 2019. We separated patients into groups of main and bilateral PAB and described their outcomes, focusing on patients with main PAB. RESULTS: This study identified 3367 PAB procedures from 2016 to 2019 (3% of all STS CHSD cardiovascular cases during this period): 2677 main PAB, 690 bilateral PAB. Operative mortality was 8% after main PAB and 26% after bilateral PAB. There was significant variation in use of main PAB by center, with 115 centers performing at least 1 main PAB procedure (range, 1-134; Q1-Q3, 8-33). For patients with main PAB, there were substantial differences in mortality, depending on timing of main PAB relative to other procedures. The highest operative mortality (25%; P < .0001) was in patients who underwent main PAB after another separate procedure during their admission, with extracorporeal membrane oxygenation being the most frequent preceding procedure. CONCLUSIONS: PAB is a frequently used congenital cardiac procedure with high mortality and variation in use across centers. Outcomes vary widely by banding type and patient diagnosis. Main PAB after cardiac surgical procedures, especially extracorporeal membrane oxygenation, is associated with very high operative mortality.

Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity.

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics.

Impact of Age-related change in Caval Flow Ratio on Hepatic Flow Distribution in Fontan.

Background: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac (EC) conduit or a lateral tunnel (LT) connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. Objective: The effect of age-related changes in caval inflows on HFD was evaluated using cardiac MRI (CMR) data and patient-specific computational fluid dynamics (CFD) modeling. Methods: SVC and IVC flow from 414 Fontan patients were collected to establish a relationship between SVC:IVC flow ratio and age. CFD modeling was performed in 60 (30 EC and 30 LT) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. Results: SVC:IVC flow ratio inverted at ∼8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC = 2,1, and 0.5 corresponded to ages 3, 8, and 15+ respectively) was not significant for EC but statistically significant for LT cohorts. For all three caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2→0.5 (age 3→15+), the correlation's strength decreased from 0.87→0.64, due to potential flow perturbation as IVC flow momentum increased. Conclusion: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of including SVC:IVC variations over time to understand Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes. Clinical Perspective: With improvement in standard of care and management of single ventricle patients with Fontan physiology, the population of adults with Fontan circulation is increasing. Consequently, there is a clinical need to comprehend the impact of patient growth on Fontan hemodynamics. Using CMR data, we were able to quantify the relationship between changing caval inflows and somatic growth. We then used patient-specific computational flow modeling to quantify how this relationship affected the distribution of long-term hepatic flow in extracardiac and lateral tunnel Fontan types. Our findings demonstrated the significance of including SVC:IVC changes over time in CFD modeling to learn more about the long-term hemodynamics of Fontan. Fontan surgical approaches are increasingly planned and optimized using computational flow modeling. For a patient undergoing a Fontan procedure, the workflow presented in this study that takes into account the variations in Caval inflows over time can aid in predicting the long-term hemodynamics in a planned Fontan pathway.

The Academic Impact of Congenital Heart Surgeons' Society (CHSS) Studies.

PURPOSE: We reviewed all 64 articles ever published by The Congenital Heart Surgeons' Society (CHSS) Data Center to estimate the academic impact of these peer-reviewed articles. MATERIALS AND METHODS: The Congenital Heart Surgeons' Society has performed research based on 12 Diagnostic Inception Cohorts. The first cohort (Transposition) began enrolling patients on January 1, 1985. We queried PubMed to determine the number of publications that referenced each of the 64 journal articles generated by the datasets of the 12 Diagnostic Inception Cohorts that comprise the CHSS Database. Descriptive summaries of the data were tabulated using mean with standard deviation and median with range. RESULTS: Sixty-four peer-reviewed papers have been published based on the CHSS Database. Fifty-nine peer-reviewed articles have been published based on the 12 Diagnostic Inception Cohorts, and five additional articles have been published based on Data Science. Excluding the recently established Diagnostic Inception Cohort for patients with Ebstein malformation of tricuspid valve, the number of papers published per cohort ranged from 1 for coarctation to 11 for transposition of the great arteries. The 11 articles generated from the CHSS Transposition Cohort were referenced by a total of 111 articles (median number of references per journal article = 9 [range = 0-22, mean = 10.1]). Overall, individual articles were cited by an average of 11 (mean), and a maximum of 41 PubMed-listed publications. Overall, these 64 peer-reviewed articles based on the CHSS Database were cited 692 times in PubMed-listed publications. The first CHSS peer-reviewed article was published in 1987, and during the 35 years from 1987 to 2022, inclusive, the annual number of CHSS publications has ranged from 0 to 7, with a mean of 1.8 publications per year (median = 1, mode = 1). CONCLUSION: Congenital Heart Surgeons' Society studies are widely referenced in the pediatric cardiac surgical literature, with over 10 citations per published article. These cohorts provide unique information unavailable in other sources of data. A tool to access this analysis is available at: [https://data-center.chss.org/multimedia/files/2022/CAI.pdf].

World Journal for Pediatric and Congenital Heart Surgery-The Official Journal of the Congenital Heart Surgeons' Society.

The World Journal for Pediatric and Congenital Heart Surgery (WJPCHS) was established in 2009, as a means of advancing the educational and scholarship goals of the World Society for Pediatric and Congenital Heart Surgery. WJPCHS has grown steadily since the first issue was published in April 2010. In 2017, the Congenital Heart Surgeons' Society and the European Congenital Heart Surgeons Association both designated WJPCHS as the official journal of their respective organizations. The CHSS and ECHSA represent the face and the voice of congenital heart surgery in North America (United States and Canada) and in Europe, respectively. Each organization has advanced the science of surgical management of congenital heart disease through multicenter outcomes analyses, which have strongly and positively influenced the care of patients around the world.

Voided volume may not impact stone outcomes: Review of a large institutional nephrolithiasis cohort.

Background: Urologic guidelines universally recommend increasing fluid intake for kidney stone prevention. Increased voided volume is thought to help reduce stone recurrence and severity, but supporting evidence is limited. Patients and Methods: Nephrolithiasis outcomes and 24-h urine data for patients from the Registry for Stones of the Kidney and Ureter (ReSKU), a registry of nephrolithiasis patients collected between 2015 and 2020, were retrospectively analysed. Outcome was stone events, either an office visit where a patient reports symptomatic passage of stones or surgery for stone removal. Results: We identified 450 stone patients with 24-h urine and kidney stone outcome data. There was no significant difference in 24-h voided volume between patients with one stone event and patients with two or more stone events. On multivariable logistic regression, after controlling for age, gender, BMI, and 24-h sodium and creatinine per kilogram, no significant associations were found between voided volume and stone events. There was a statistically significant negative correlation noted between voided volume and stone events in calcium oxalate dihydrate stone formers (Spearman R = -0.42, p = 0.04), but not others. Conclusions: Twenty-four-hour voided volume was not associated with stone events in a large institutional cohort, and subset analysis reveals that some stone formers may benefit more from increased voided volume than others; identifying such patients represents a novel precision medicine opportunity.

High-Throughput Screening and Proteomic Characterization of Compounds Targeting Myeloid-Derived Suppressor Cells.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population of incompletely differentiated immune cells. They are known to suppress T cell activity and are implicated in multiple chronic diseases, which make them an attractive cell population for drug discovery. Here, we characterized the baseline proteomes and phospho-proteomes of mouse MDSC differentiated from a progenitor cell line to a depth of 7000 proteins and phosphorylation sites. We also validated the cellular system for drug discovery by recapitulating and identifying known and novel molecular responses to the well-studied MDSC drugs entinostat and mocetinostat. We established a high-throughput drug screening platform using a MDSC/T cell coculture system and assessed the effects of ∼21,000 small molecule compounds on T cell proliferation and IFN-γ secretion to identify novel MDSC modulator. The most promising candidates were validated in a human MDSC system, and subsequent proteomic experiments showed significant upregulation of several proteins associated with the reduction of reactive oxygen species (ROS). Proteome-wide solvent-induced protein stability assays identified Acyp1 and Cd74 as potential targets, and the ROS-reducing drug phenotype was validated by measuring ROS levels in cells in response to compound, suggesting a potential mode of action. We anticipate that the data and chemical tools developed in this study will be valuable for further research on MDSC and related drug discovery.

Global taxonomic, functional, and phylogenetic diversity of bees in apple orchards.

An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators and identification of the drivers of pollinator community changes across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated diversity drivers for 644 bee species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographical biomes. Our findings reveal significant taxonomic dissimilarity among biogeographical zones. Interestingly, despite this dissimilarity, species from different zones share similar higher-level phylogenetic groups and similar ecological and behavioural traits (i.e. functional traits), likely due to habitat filtering caused by perennial monoculture systems managed intensively for crop production. Honey bee species dominated orchard communities, while other managed/manageable and wild species were collected in lower numbers. Moreover, the presence of herbaceous, uncultivated open areas and organic management practices were associated with increased wild bee diversity. Overall, our study sheds light on the importance of large-scale analyses contributing to the emerging fields of functional and phylogenetic diversity, which can be related to ecosystem function to promote biodiversity as a key asset in agroecosystems in the face of global change pressures.