Faculty Bibliography

Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05-1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR_{per SD} = 1.12, 95% CI: 1.02-1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

Tumor biologic risk has replaced anatomic disease burden for guiding chemotherapy use in HR-positive, early-stage breast cancer. Recent surgical trials support less frequent axillary lymph node dissection, potentially impacting incidence of N2-3 diagnoses. As the field considers applying genomic risk assessment tools for locally advanced, operable HR-positive breast cancer, we estimated current incidence of these cancers, focusing on HR-positive/HER2-negative disease. Of 486,031 cases recorded with Stage I-III HR-positive/HER2-negative disease in the U.S. National Cancer Institute Surveillance, Epidemiology, and End Results-17 database (2010-2021), 28,585 (5.9%) and 23,307 (4.8%) had N2-3M0(Any T) and T3-4N0-1M0 disease, respectively. Invasive lobular cancer, observed across all disease stages and receptor-based subtypes, was highest in HR-positive/HER2-negative locally advanced disease. Incidence of N2-3M0(Any T) decreased for each subtype. Incidence of T3-4N0-1M0 increased for HR-positive/HER2-negative disease but not for the other subtypes. Defining chemotherapy benefit for patients with locally advanced, operable HR-positive breast cancer remains an important clinical question.

OBJECTIVE:To examine associations between oxidative stress and fetal weight across pregnancy. STUDY DESIGN/METHODS:Cohort study of pregnant participants from 2016-2021 in New York City with urinary lipid, protein, and DNA oxidative stress biomarkers (<18, 18-25, >25 weeks) and estimated fetal weight from ultrasound fetal biometry with the HadlockIII formula (20, 30, 36 weeks). RESULT/RESULTS:percentile. Oxidative stress biomarkers of protein damage were associated with larger estimated fetal weight at 20 (3.4 [95% CI: 1.2, 5.7]) and 36 weeks (16.5 [95% CI: 5.2, 27.8]). CONCLUSION/CONCLUSIONS:These findings advance our understanding of different oxidative stress pathways and their potential role in fetal growth.

BACKGROUND:The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood. METHODS:We investigated associations of genetic susceptibility to type 2 diabetes (T2D), eight T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242,283 cases, 1,569,734 controls), T1D (18,942 cases, 501,638 controls), and PDAC (10,244 cases and 360,535 controls) in individuals of European ancestry. RESULTS:Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI 1.05-1.15), particularly the T2D obesity (OR = 1.28; 95% CI 1.15-1.42) and lipodystrophy (OR = 1.25; 95% CI 1.03-1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI 0.99-1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10-8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10-4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions. CONCLUSIONS:Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.

OBJECTIVE:To determine whether administration of antenatal corticosteroids to patients with twin gestations at risk for late preterm delivery is associated with reduced risk for neonatal respiratory morbidity compared with unexposed twins. METHODS:This was a multicenter, retrospective cohort study in a large, urban health network (2013-2022) of patients with twin gestations at risk for preterm delivery between 34 0/7 and 36 6/7 weeks of gestation. Patients were excluded if they received antenatal corticosteroids before 34 weeks of gestation or had pregestational diabetes, single-twin death before 34 weeks, or oral steroid exposure during pregnancy. Neonates were excluded if they had major congenital anomalies. The primary outcome was a composite of neonatal respiratory morbidity requiring respiratory support within 72 hours of birth, including continuous positive airway pressure (CPAP) or high-flow nasal cannula for 2 hours or more, supplemental oxygen of 30% for 2 hours or more, extracorporeal membrane oxygenation, mechanical ventilation, and fetal or neonatal death. Secondary outcomes included neonatal hypoglycemia and indications for neonatal intensive care unit (NICU) admission. Adjusted and unadjusted relative risks with 95% CIs were calculated. RESULTS:During the study period, 366 twin gestations and 722 patient-neonate dyads were included: 162 gestations (321 neonates) in the exposed group and 204 (401 neonates) in the unexposed group. There was no difference in the composite outcome of respiratory morbidity in those exposed to antenatal corticosteroids (23.4% vs 20.4%, P=.40, adjusted relative risk [RR] 1.00, 95% CI, 0.71-1.42). The composite was driven mostly by rates of CPAP use (21.2% vs 18.5%, P=.41, adjusted RR 1.05, 95% CI, 0.73-1.53) and high-flow nasal cannula use (6.2% vs 2.2%, P=.02, RR 2.77, 95% CI, 1.16-6.66). Antenatal corticosteroid exposure was associated with a lower risk of need for supplemental oxygen (0.6% vs 3.5%, P=.02, RR 0.18, 95% CI, 0.04-0.79) and mechanical ventilation (0.6% vs 3.2%, P=.03, RR 0.19, 95% CI, 0.04-0.87). Although antenatal corticosteroids exposure was not associated with higher rates of hypoglycemia (44.2% vs 41.7%, P=.57, adjusted RR 0.99, 95% CI, 0.82-1.19), exposure was associated with a higher risk of having hypoglycemia as the only indication for NICU admission (10.3% vs 5.2%, P=.03, RR 1.96, 95% CI, 1.07-3.59). CONCLUSION/CONCLUSIONS:In a large, multicenter, network-wide retrospective cohort study of patients with twin gestations at risk for late preterm birth, antenatal corticosteroid use was not associated with a decrease in overall respiratory morbidity but was associated with a decreased risk of need for supplemental oxygen and mechanical ventilation, as well as a higher risk of NICU admission for hypoglycemia. These results underscore the ongoing need to elucidate the risks and benefits of late preterm antenatal corticosteroids for patients with twin gestations at risk for late preterm birth.

OBJECTIVE:To examine current Complex Family Planning (CFP) fellows' experience with induction of fetal asystole. STUDY DESIGN/METHODS:Cross-sectional web-based survey of trainees enrolled in United States accredited CFP fellowships. RESULTS:Of the 52/66 (79%) of fellows who responded, 36/52 (69%) plan to provide induction of fetal asystole post-fellowship. Thirty-six (69%) received training, most commonly by digoxin (31/52, 60%) transabdominal (31/31, 100%) intrafetal (26/31, 83%) injections. Twenty-four (46%) predicted competence upon graduation. CONCLUSIONS:CFP fellowship programs can expand availability and comprehensiveness of training to support graduates in independent practice of induction of fetal asystole.

BACKGROUND:The approach to prevent eclampsia in the postpartum period utilizes magnesium sulfate but there is no evidence-based standard to guide duration. OBJECTIVES/OBJECTIVE:To assess the cost-effectiveness of an abbreviated 12-hour postpartum magnesium sulfate regimen compared with a standard 24-hour regimen. STUDY DESIGN/METHODS:A decision-analytic model was constructed to compare a 12-hour regimen with a 24-hour regimen in a theoretical cohort of 45,800 patients with preeclampsia with severe features. Probabilities, costs, and utilities were derived from the literature. Primary outcomes included incremental cost per quality-adjusted life-year (QALY), cases of eclampsia, magnesium toxicity, and maternal death. The cost-effectiveness threshold was $100,000 per QALY. RESULTS:A 12-hour regimen in this theoretical cohort of 45,800 postpartum patients compared with a 24-hour regimen resulted in 86 more cases of eclampsia (398 vs 312) and 0.37 more deaths (10.87 vs 10.50). However, there were 656 fewer cases of magnesium toxicity (2089 vs 2745). Overall, a 12-hour regimen was a dominant strategy that resulted in decreased costs of $21.5 million and increased effectiveness of 17 QALYs. CONCLUSION/CONCLUSIONS:In our study, an abbreviated duration of postpartum magnesium sulfate prophylaxis for patients with preeclampsia with severe features was a dominant strategy (lower costs, better outcomes) and cost-effective compared with the standard 24-hour regimen.