Faculty Bibliography

The objective of this systematic review was to identify the evidence of testicular cancer risk for people with intersex conditions. This assessment is hoped to help refine risk stratification tools for assessing gonadal malignancy risk and guide the development of more robust evidence-based management strategies. The literature was searched in Ovid MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health using a search string developed by a multidisciplinary team. The protocol was registered at Prospective Register of Systematic Reviews as CRD42021231313. A total of 3608 articles were found. After selection, 301 publications were included (1215 individuals). The results identified significant evidence that pre-pubertal gonadectomy may be linked to lower rates of malignant gonadal changes for patients with partial gonadal dysgenesis, Turner's syndrome with Y-chromosome material, complete androgen insensitivity, partial androgen insensitivity, and patients with ovotestis/es. The evidence was not significant for patients with complete gonadal dysgenesis, Klinefelter syndrome, nor WT1-related syndromes. Specific cancer outcomes were unable to be assessed due to small sample sizes and thus it is unknown if clinically significant cancer outcomes are meaningfully altered by pre-pubertal gonadectomy. Importantly, the quality of data on the topic of gonadal malignancy in intersex patients with testicular tissue was determined to be poor overall. The quality was relatively more robust regarding the conditions of Complete Androgen Insensitivity, Klinefelter syndrome, and patients with ovotestis/es. More high-quality research is needed to draw specific conclusions on the risks and benefits of performing pre-pubertal gonadectomy for intersex patients. When counseling these patients, clinicians should be transparent regarding the paucity of data supporting pre-pubertal gonadectomy.

BACKGROUND:Midkine is a heparin-binding growth factor that is overexpressed in most human malignancies, including breast cancer. While elevated midkine levels have been associated with tumor progression and aging, its role as a predictive biomarker for breast cancer risk in healthy individuals remains unclear. We previously showed that higher midkine expression in estrogen receptor-positive (ER +) breast cancer in younger (< 55) women is associated with shorter disease-free survival. We investigated whether serum midkine levels in premenopausal women are associated with subsequent risk of ER + breast cancer. METHODS:We conducted a prospective, nested case-control study within the New York University Women's Health Study (NYUWHS). Serum midkine levels were measured in baseline blood samples from 249 premenopausal women who developed ER + breast cancer more than 10 years after blood collection and 249 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) across quartiles and continuous midkine levels, adjusting for key breast cancer risk factors. RESULTS:Higher circulating midkine levels were associated with a marginally statistically significant lower risk of ER + breast cancer. Compared to the lowest quartile, women in the highest quartile had an OR of 0.55 (95% CI: 0.30-0.99; P for trend = 0.10). A doubling in midkine was associated with a 34% reduction in risk (OR = 0.66; 95% CI: 0.42-1.02). The inverse association was generally consistent across subgroups. CONCLUSION/CONCLUSIONS:These findings suggest that higher baseline serum midkine levels in premenopausal women are associated with a reduced long-term risk of ER + breast cancer. This challenges prior assumptions about midkine's uniformly pro-tumorigenic role and suggests it may be a context-dependent biomarker in breast cancer development.

STUDY QUESTION/OBJECTIVE:Is there an association between infertility diagnosis and long-term adult-onset psychiatric conditions in women? SUMMARY ANSWER/CONCLUSIONS:Infertility diagnosis in women is linked to higher risks of mood disorders, anxiety- and stress-related disorders, and behavioral syndromes with physical components, but not schizophrenia or other psychotic disorders, particularly notable from 9 years after the first infertility diagnosis. WHAT IS KNOWN ALREADY/BACKGROUND:Infertility, especially in women, is associated with major mental health challenges around the time of diagnosis. However, the long-term connection with a wide range of psychiatric disorders is largely unknown. STUDY DESIGN, SIZE, DURATION/METHODS:This study employed a matched-pair design within the UK Biobank (UKB) cohort, including 3893 females with a diagnosis of infertility and 15 603 matched female controls, totaling 19 496 participants. PARTICIPANTS/MATERIALS, SETTING, METHODS/METHODS:Female UKB participants with a diagnosis of infertility were matched to females without the diagnosis in a 1:4 ratio based on year of birth, index of deprivation of their residency area, and primary care data linkage status. The diagnosis of female infertility was identified by the first occurrence of a primary or secondary diagnosis in either primary care or hospital records. Additional analyses explored interactions between infertility diagnosis and both miscarriage and childbearing status on psychiatric conditions. MAIN RESULTS AND THE ROLE OF CHANCE/RESULTS:Diagnosis of infertility was associated with higher risks of mood disorders, anxiety- and stress-related disorders, and behavioral syndromes with physical components, but not with schizophrenia or other psychotic disorders. The most notable increases in the risk of psychiatric diagnoses were observed 9 years after the first infertility diagnosis. No significant interactions were found between infertility diagnosis and either miscarriage or childbearing status on psychiatric conditions. Sensitivity analysis confirmed the robustness of these associations across different data sources for infertility diagnosis and psychiatric condition ascertainment. LIMITATIONS, REASONS FOR CAUTION/CONCLUSIONS:The study's limitations include the racial homogeneity and the overall healthier status of the UKB cohort compared to the general UK population and the potential underestimation of associations due to misclassification of subfecund women. WIDER IMPLICATIONS OF THE FINDINGS/CONCLUSIONS:These results emphasize the need for integrated mental health support in infertility care and long-term monitoring of infertility patients for psychiatric risks. STUDY FUNDING/COMPETING INTEREST(S)/BACKGROUND:None. No competing interests were declared. TRIAL REGISTRATION NUMBER/BACKGROUND:n/a.

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.

Increasing the vaginal birth after cesarean (VBAC) rate to 18% was a Healthy People 2020 goal. Detailed data on racial/ethnic differences in VBAC rates is lacking and can inform efforts to equitably increase VBAC rates. This study aimed to assess racial/ethnic variation in VBAC rates and to describe group trends in VBAC rates in California between 2011 and 2021.This retrospective cohort study used a database of birth certificates linked to hospital discharge records. We analyzed singleton, term live births among people who had a history of at least one prior cesarean birth, no identified contraindications to a vaginal birth, and self-identified their racial/ethnic group as Hispanic or non-Hispanic (American Indian-Alaskan Native (AIAN), Asian, Black, Hawaiian/Pacific Islander, or white). VBAC births were identified from birth certificate records. Differences between VBAC rates were assessed using univariable and multivariable Poisson log-linear regression while adjusting for potential confounders.A total of 607,808 birthing people were included (2,234 AIAN, 84,899 Asian, 34,217 Black, 2,559 Hawaiian/Pacific Islander, 334,116 Hispanic, 149,783 white). Over the study period, Hawaiian/Pacific Islander birthing people had the highest average VBAC rate at 11.5% (AIAN, 6.5%; Asian, 8.8%; Black, 8.0%; Hispanic, 7.4%; white, 9.5%). In adjusted models, Black (aRR = 1.06, 95% CI: 1.01-1.11) and Hawaiian/Pacific Islander (aRR = 1.43, 95% CI: 1.27-1.61) birthing people were more likely to have a VBAC compared with white birthing people, while Hispanic birthing people were less likely (aRR = 0.96, 95% CI: 0.93-0.98). VBAC rates increased significantly (p < 0.001) over time for all groups except AIAN birthing people.VBAC rates increased for most racial/ethnic groups in California. With the exception of the Hawaiian/Pacific Islander group, there were small and likely not clinically significant differences in the chances for a VBAC across groups. No group in California met the Healthy People 2020 goal VBAC rate of 18%. · VBAC rates increased for most racial/ethnic groups.. · The VBAC rate for AIAN birthing people did not increase.. · No group met the Healthy People 2020 goal VBAC rate of 18%..

OBJECTIVE:This study aimed to explore the demographic and clinical factors associated with delayed initiation of treatment for patients with cervical cancer treated with chemoradiation and brachytherapy and determine its impact on oncologic outcomes. METHODS:Patients with stage IB2 to IVA cervical cancer who were treated with definitive chemoradiation therapy and brachytherapy from 2009 to 2019 were included. Patients who initiated treatment within 8 weeks of diagnosis (early) were compared with those who initiated treatment after 8 weeks (delayed). Time intervals at each stage of care and reasons for delay were evaluated. Logistic regression was performed to identify factors associated with delayed treatment initiation. Cox regression analyzed factors associated with progression-free and overall survival. RESULTS:Of 122 patients, 76 (62%) initiated early treatment, with a median time to treatment of 35 days, and 46 (38%) underwent delayed treatment initiation, with 76 median days to treatment. Patients referred from the public hospital were more likely to experience delayed treatment than those referred from the private hospital (odds ratio 4.31, 95% confidence interval [CI] 1.31 to 14.07). Most delays were due to system factors (85%). Each 10-day increase in time to treatment initiation was associated with worsened overall survival (hazard ratio [HR] 1.07, 95% CI 1.01 to 1.13). Public hospital patients were more likely to experience delays but were less likely to present with advanced stage (29% vs 50%, p = .031) and had improved overall survival compared with patients referred from the private hospital (HR 0.37, 95% CI 0.16 to 0.87). CONCLUSIONS:Treatment initiation delays were associated with a decrement in survival. In this cohort, public hospital patients were more likely to have a favorable stage and improved survival than those from the private hospital but also were more likely to experience treatment initiation delays. Referral patterns and delays related to diagnostic workup were the most common factors contributing to delays in care establishment. Improving care coordination may ensure equitable access to timely staging and treatment. Further studies are needed to determine whether treatment initiation delays impact cancer outcomes.

Cesarean deliveries are associated with uterine scar defects that significantly impact women's health and future pregnancy outcomes. The methods used for hysterotomy closure following cesarean delivery have undergone significant evolution. Commonly used techniques, which are relatively rapid and maintain hemostasis, include the endometrium in a single-layer or "bulk" closure. Such endometrium-inclusive cesarean closure has been linked to an increased risk of scar defects and long-term complications. However, the available data show no difference in outcomes related to cesarean closure technique, leading to widespread adoption of single-layer closure. The debate over the best method for uterine closure as well as the etiology of scar defects remains unresolved. We present the endometrium-free closure technique, an approach that requires in-depth knowledge of uterine anatomy, including the ability to distinguish the 3 layers of the uterine wall, and employs reapproximation of these layers. A 30-year retrospective study of consecutive cesarean deliveries using this closure method reports a reduction in abnormal implantation in subsequent pregnancies. Key findings from sonohysterographic studies demonstrate a clinically significant reduction in the development and size of scar defects when the endometrium is excluded from the closure, in women with one or multiple cesarean deliveries. While formal changes in surgical guidelines may require further randomized trials, we believe that this technique has the potential to reduce adverse events and provide long-term benefits for women's reproductive health.

OBJECTIVE:Social determinants of health (SDOH) may impact the incidence of Respiratory Syncytial Virus (RSV) infection and the uptake of vaccinations in pregnancy. The objective of this study is to identify contributors to disparities in RSV vaccination in pregnancy. DESIGN/METHODS:This is a retrospective cohort study of patients delivering at term within three hospitals during February and March 2024, comparing pregnant patients identified as receiving vs not receiving RSV vaccinations. This period and gestational age were chosen to include patients who would have qualified for RSV vaccination administration. Vaccination status was extracted from standardized admission templates where these variables were recorded as discrete fields. Patients without RSV vaccination information were excluded. Sociodemographic factors, COVID vaccination status, and delivery campus were evaluated. Outcomes were analyzed using chi-squared, t-test, and McNemar test. RESULT/RESULTS:2181 patients met inclusion criteria and RSV vaccination information was available for 1548 patients (71%) with a 14% vaccination rate. Compared to those not vaccinated (n=1332), RSV vaccinated patients (n=216) were more likely to be older (30.7 vs 34.8, p<0.001), have private insurance (42% vs 85%, p<0.001), speak English (82% vs 95%, p<0.001), and deliver at our regional perinatal center (26% vs 77%, p<0.001). 50% of RSV vaccinated patients had a history of COVID vaccination compared to 33% of those not vaccinated against RSV (p<0.001). CONCLUSIONS:SDOH were associated with differences in RSV vaccination status. In addition, patients without RSV vaccination were less likely to have had COVID vaccination. These findings highlight the need to address SDOH to increase vaccination rates for vulnerable populations.

The incidence of maternal cardiac arrest is rising, paralleling the escalating maternal morbidity and mortality rates in the United States. Effective management of cardiac arrest in pregnancy requires timely initiation of a resuscitative cesarean delivery when indicated. Understanding the history, indications, maternal physiology, and surgical principles of resuscitative cesarean delivery is essential for all clinicians caring for pregnant patients. Resuscitative measures during maternal cardiac arrest have evolved through the centuries-beginning as a burial practice for both mother and baby, evolving further to attempt fetal salvage, and now, to maternal rescue. During this evolution, performing resuscitative cesarean delivery was most effective if initiated within 4 minutes of maternal cardiac arrest. This concept led to the term "4-minute rule" or the principle of initiating a resuscitative cesarean delivery within 4 minutes of arrest to optimize maternal and fetal outcomes. Furthermore, the terminology has also progressed. "Resuscitative cesarean delivery" is now preferred over "perimortem cesarean delivery," emphasizing the goal of maternal resuscitation rather than fetal salvage. Successful maternal resuscitation may occur from resuscitative cesarean delivery due to relieving aortocaval compression by the gravid uterus, thus restoring venous return and cardiac output. Additional benefits include an autotransfusion effect from the uteroplacental circulation and improved oxygenation. Due to this aspect of maternal physiology, resuscitative cesarean delivery is indicated when maternal cardiac arrest occurs at 20 weeks' gestation or greater, or when the fundus is at the level of the umbilicus and should be considered immediately upon cardiac arrest in term patients or in those arriving pulseless from the prehospital setting. Rapid bedside initiation of resuscitative cesarean delivery is critical; transporting the patient to the operating room causes harmful delays. Training multidisciplinary teams to perform resuscitative cesarean delivery at the site of arrest can improve adherence to the "4-minute rule" and survival rates. Surgical technique prioritizes speed and simplicity, favoring a vertical midline skin incision and a vertical uterine incision to minimize vascular injury and facilitate rapid uterine evacuation. Postprocedure, recovery is optimized by proper wound management via broad-spectrum antibiotics and consideration of delayed wound closure, stabilization of uterine hemostasis, and careful application of critical care in the postpartum setting. In summary, resuscitative cesarean delivery is a critical, life-saving intervention during maternal cardiac arrest, providing physiological decompression, enhancing maternal resuscitation efforts, and improving neonatal outcomes. Resuscitative cesarean delivery substantially improves the chances of maternal return of spontaneous circulation and fetal survival in cases of maternal cardiac arrest. Given the persistent rise in maternal morbidity and mortality, increased awareness and readiness to perform resuscitative cesarean delivery using protocolized training and interdisciplinary coordination are imperative to improving maternal and perinatal outcomes in the modern healthcare landscape.

INTRODUCTION AND HYPOTHESIS/OBJECTIVE:Patients with stage 3 or 4 pelvic organ prolapse (POP) may concurrently have hydronephrosis. Consequences of hydronephrosis, such as acute kidney injury and chronic kidney disease, have significant costs to patients and healthcare facilities. In this study, we evaluate the cost-effectiveness of renal ultrasound to screen for hydronephrosis in patients with stage 3 or 4 POP. METHODS:We designed a decision tree model comparing screening renal ultrasound versus usual care for patients with stage 3 or 4 POP. In the screening strategy, patients undergo ultrasound and subsequently proceed with pessary or surgery should they screen positive for hydronephrosis or proceed with expectant management, pessary, or surgery should they screen negative. In the non-screening strategy, patients choose treatment as they normally would and those with underlying hydronephrosis either continue to have hydronephrosis or have resolution of hydronephrosis. We modeled a time horizon of 5 years, with a 3% discount rate annually for future costs and quality-adjusted life-years (QALY). This was an IRB-exempt study. RESULTS:At a willingness to pay threshold of $150,000/QALY, renal ultrasound was cost-effective when the majority of patients who screen positive for hydronephrosis choose pessary instead of surgery. Screening renal ultrasound is cost-effective if less than 36.3% of patients with hydronephrosis choose surgery. At 5 years, screening renal ultrasound was cost-effective regardless of the prolapse treatment chosen by patients with hydronephrosis. CONCLUSION/CONCLUSIONS:Routine renal ultrasound screening of patients with stage 3 or 4 POP is a cost-effective strategy to identify hydronephrosis and guide treatment that mitigates risk of permanent renal damage.