Differences in Acute Graft-Versus-Host Disease (GVHD) Severity and Its Outcomes Between Black and White Patients.

Acute graft-versus-host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation (HCT). Although recent advancements in GVHD prophylaxis have resulted in successful HCT across HLA barriers and expanded access to HCT for racial minorities, less is known about how race affects the severity and outcomes of acute GVHD. This study examines differences in the clinical course of acute GVHD and the prognostic value of GVHD biomarkers for Black and White recipients. We conducted a retrospective analysis of patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) database who underwent HCT between 2014 and 2021 to describe the difference in clinical course of acute GVHD and significance of GVHD biomarkers between Black and White recipients. We used propensity score matching to generate a 1:3 matched cohort of 234 Black patients and 702 White patients with similar baseline characteristics. In the first year after HCT Black patients experienced a higher cumulative incidence of grade III-IV acute GVHD (17% versus 12%, P = 0.050), higher nonrelapse mortality (NRM; 18% versus 12%, P = .009), and lower overall survival that trended toward statistical significance (73% versus 79%, P = .071) compared to White patients. The difference in NRM in the first year was even greater among Black patients who developed GVHD than White patients (24% versus 14%, P = .041). The distribution of low, intermediate, and high MAGIC biomarker scores at the time of treatment was similar across racial groups (P = .847), however, Black patients with high biomarker scores experienced significantly worse NRM than White patients (71% versus 32%, P = .010). Our data indicate that Black patients are at a higher risk of NRM following HCT, primarily from a higher incidence of severe GVHD. Serum biomarkers at treatment initiation can stratify patients for risk of NRM across races, however Black patients with high biomarker scores had a significantly greater NRM risk. These results suggest a need for strategies that mitigate the higher risk for poor GVHD outcomes among Black patients.

A genome-wide association study of social trust in 33,882 Danish blood donors.

Social trust is a heritable trait that has been linked with physical health and longevity. In this study, we performed genome-wide association studies of self-reported social trust in n = 33,882 Danish blood donors. We observed genome-wide and local evidence of genetic similarity with other brain-related phenotypes and estimated the single nucleotide polymorphism-based heritability of trust to be 6% (95% confidence interval = (2.1, 9.9)). In our discovery cohort (n = 25,819), we identified one significantly associated locus (lead variant: rs12776883) in an intronic enhancer region of PLPP4, a gene highly expressed in brain, kidneys, and testes. However, we could not replicate the signal in an independent set of donors who were phenotyped a year later (n = 8063). In the subsequent meta-analysis, we found a second significantly associated variant (rs71543507) in an intergenic enhancer region. Overall, our work confirms that social trust is heritable, and provides an initial look into the genetic factors that influence it.

Deep integrative models for large-scale human genomics.

Polygenic risk scores (PRSs) are expected to play a critical role in precision medicine. Currently, PRS predictors are generally based on linear models using summary statistics, and more recently individual-level data. However, these predictors mainly capture additive relationships and are limited in data modalities they can use. We developed a deep learning framework (EIR) for PRS prediction which includes a model, genome-local-net (GLN), specifically designed for large-scale genomics data. The framework supports multi-task learning, automatic integration of other clinical and biochemical data, and model explainability. When applied to individual-level data from the UK Biobank, the GLN model demonstrated a competitive performance compared to established neural network architectures, particularly for certain traits, showcasing its potential in modeling complex genetic relationships. Furthermore, the GLN model outperformed linear PRS methods for Type 1 Diabetes, likely due to modeling non-additive genetic effects and epistasis. This was supported by our identification of widespread non-additive genetic effects and epistasis in the context of T1D. Finally, we constructed PRS models that integrated genotype, blood, urine, and anthropometric data and found that this improved performance for 93% of the 290 diseases and disorders considered. EIR is available at https://github.com/arnor-sigurdsson/EIR.

Perioperative Complications of Cesarean Delivery Myomectomy: A Meta-analysis.

OBJECTIVE: To assess the association of myomectomy during cesarean delivery with intraoperative and perioperative maternal morbidity. DATA SOURCES: We searched MEDLINE (1966-2017), Scopus (2004-2017), ClinicalTrials.gov (2008-2017), EMBASE (1980-2017), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases. METHODS OF STUDY SELECTION: We selected all observational studies that reported outcomes on patients undergoing myomectomy at the time of cesarean delivery. Statistical meta-analysis was performed with RevMan 5.3. RESULTS: Nineteen studies were included in our systematic review with a total number of 3,900 women. Among them, 2,301 women had myomectomy during cesarean delivery and 1,599 had cesarean delivery only. Women undergoing concomitant myomectomy had a mild decline in hemoglobin compared with those who had cesarean delivery only (mean difference 0.25 mg/dL, 95% CI 0.06-0.45). Myomectomy at the time of cesarean delivery is associated with longer surgical time compared with cesarean delivery alone (mean difference 13.87 minutes, 95% CI 4.78-22.95). Blood transfusion (odds ratio [OR] 1.41, 95% CI 0.96-2.07) and postoperative fever (OR 1.12, 95% CI 0.80-1.56) rates did not differ between the two groups (myomectomy compared with no myomectomy). A statistically, but not clinically, significant increase in postoperative hospitalization was evident in the myomectomy group (mean difference 0.35 days, 95% CI 0.25-0.46). CONCLUSION: This systematic review and meta-analysis of observational studies demonstrated an association with increased operative time and hemoglobin drop in patients who underwent cesarean myomectomy compared with cesarean delivery alone. No increased rate of major hemorrhage or need for transfusion was identified. Cesarean myomectomy may be considered in cases of isolated myomas, although randomized trials are needed.