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.

PURPOSE/OBJECTIVE:The National Academy of Science Engineering and Medicine (NASEM) developed items to collect sexual orientation and gender identity (SOGI) in healthcare settings to harmonize collection of these data and address disparities often experienced by sexual and gender minorities (SGM) (LGBTQAI+). This study tested wording of SOGI items among the SGM Community. METHODS:Individuals were recruited to participate in an interview about the NASEM SOGI items. Eligible participants identified as SGM, lived within the catchment area of an NYC academic medical center, had a history of cancer, or were caregivers of a person with cancer. Interviews were audio-recorded, transcribed, and qualitatively coded. RESULTS:Thirty-eight SGM individuals participated. The majority disliked the options for sexual orientation (SO) and gender identity (GI) but did find one they would choose. For SO, participants thought options like queer, pansexual, and asexual were missing, and for GI, participants said non-binary and transgender category (transgender man, transgender woman) were needed. Half said they had no concerns about disclosing SOGI information on medical intake forms and others reported preferring knowing why it was needed and who would have access. Several expressed worry about their safety upon disclosure of SOGI. Respondents cited being less likely to disclose SOGI if there was an offensive question on intake form (e.g., spouse instead of partner) or if there were no privacy assurances. Almost all expected reported SOGI to be reflected in their oncology healthcare. CONCLUSIONS:The NASEM questions need improvement. To improve trust and encourage disclosure, clinicians and clinics should improve the options for SOGI data collection and take steps to ensure privacy is addressed.

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and infant mortality and morbidity worldwide. This prospective cohort study investigated the association of racial and ethnic disparities in HDP and explored the potential mediation effect of environmental chemical exposures on excess HDP risk among non-Hispanic Black pregnant people. A total of 3,279 pregnant people were included from 11 cohorts across the United States in the Environmental influences on Child Health Outcomes (ECHO) Program. We analyzed 20 environmental chemicals detected in over 70 % of biospecimens collected during pregnancy. Among Hispanic, non-Hispanic White, and non-Hispanic Black participants, 11.8 %, 10.8 %, and 16.6 % were diagnosed with HDP, respectively. Compared with non-Hispanic White participants, non-Hispanic Black participants had a higher risk of HDP (aRR = 1.48; 95 % CI 1.13-1.94) and higher levels of traditional phthalate metabolites, but lower levels of phthalate alternative metabolites and perfluorooctanoic acid. Hispanic participants had a lower risk of gestational hypertension (aRR = 0.62; 95 % CI 0.40-0.98) and lower levels of perfluoroalkyl substances than non-Hispanic White participants. Critically, despite these race/ethnicity-specific exposure patterns, individual chemical exposures did not mediate the association between racial/ethnic group and HDP. These findings highlight the need to investigate cumulative chemical mixtures and non-chemical environmental and social determinants as potential drivers of HDP disparities.

STUDY OBJECTIVE/OBJECTIVE:To quantify and characterize waste generated in robotic gynecologic surgery and assess its environmental impact, with the goal of identifying strategies to reduce waste and improve sustainability. DESIGN/METHODS:Waste audit and life cycle impact assessment of robotic gynecologic surgery. SETTING/METHODS:Single academic institution. PATIENTS/METHODS:Twenty robotic gynecologic surgery cases, including hysterectomies (n = 10), myomectomies (n = 6), and tubal, ovarian, or endometriosis surgeries (n = 4). INTERVENTIONS/METHODS:A detailed waste audit of all surgical waste to categorize materials into municipal solid waste (MSW) and regulated medical waste (RMW), allowing for subsequent life cycle impact assessment. MEASUREMENTS AND MAIN RESULTS/RESULTS:e (SD 0.27) per minute of operative time, with shorter surgeries producing the most emissions per minute. Cotton products contributed up to almost one-third of an impact category despite accounting for 5% of the total waste by weight. CONCLUSION/CONCLUSIONS:Opportunities to reduce the environmental impact of robotic gynecologic surgeries include reorganizing surgical kits to avoid the unnecessary opening of commonly unused items, increasing reprocessing of single-use devices, properly sorting recyclable plastics and paper products, appropriately using RMW streams, considering alternative surgical modalities for less complex cases, and exploring reusable or more environmentally-friendly alternatives to cotton and spunbond-meltblown-spunbond polypropylene products.

INTRODUCTION/BACKGROUND:Placental development, involving rapid vascularization, is regulated by concentration gradients of numerous growth factors and hormones. Placental growth factor (PlGF) promotes vasculogenesis and angiogenesis in the placenta, while soluble fms-like tyrosine kinase-1 (sFlt-1) inhibits these processes. An elevated ratio of sFlt-1/PlGF in maternal serum is predictive of preeclampsia. Exposure to two classes of ubiquitous endocrine-disrupting chemicals, bisphenols and phthalates, has also been previously linked to preeclampsia development. METHODS:We investigated the relation of urinary concentrations of bisphenols and phthalate metabolites, measured up to three times during pregnancy, with serum concentrations of sFlt-1, PlGF, and their ratio in the New York University Children's Health and Environment Study. Linear mixed models were used to analyze up to three measurements of PlGF and sFlt-1 adjusted for gestational age at the time of serum collection. RESULTS:We found that higher molar sum concentration of bisphenol A and bisphenol S was associated with lower sFlt-1 (-0.12, 95 % CI: -0.22, -0.03), higher PlGF (0.08, 95 % CI: -0.01, 0.18), and lower sFlt-1/PlGF ratio (-0.12, 95 % CI: -0.21, -0.02). Phthalic acid and metabolites of anti-androgenic and low molecular weight phthalates were similarly associated with higher PlGF and lower sFlt-1/PlGF, but only after 20 weeks of gestation. DISCUSSION/CONCLUSIONS:The unexpected relationship between prenatal bisphenol and phthalate exposure and lower sFlt-1/PlGF warrants further investigation. Our results suggest that the effect of these endocrine-disrupting chemicals on placental health may be more complicated than what is currently understood through these angiogenic biomarkers.

OnabotulinumtoxinA (onabotA) is approved for the treatment of various therapeutic indications, which require retreatment. In clinical practice, many patients receive onabotA for multiple therapeutic indications concomitantly over extended time periods; however, there is limited long-term utilization and safety data for treating comorbid indications. SYNCHRONIZE, a 2-year, multicenter, retrospective observational chart review study in 10 US clinics, describes onabotA real-world utilization and safety in adults treated for ≥2 therapeutic indications within repeating 3-month periods for up to 7 treatments. This analysis assessed the long-term onabotA safety profile for multiple therapeutic indications by analyzing the incidence of treatment-emergent adverse events (TEAEs). Of 279 patients treated for ≥2 different therapeutic indications across all treatment combination groups in Period1, there was a gradual decrease to 80 patients at the last treatment period. The overall mean onabotA treatments over the study period was 9.3 (range: 2-48). Across treatment periods, most patients had a treatment interval between different indications of ≤24 h (range: 62-98 %) and received ≥200-<400U of cumulative 3-month dosages for multiple indications (range: 43 %-50 %) with a mean 3-month dose from 231.8 to 287.0 U. In total, 28.7 % of patients reported ≥1 TEAE after Period1; this proportion remained broadly constant across treatments (range: 28.3-31.8 %). Overall, the most common TEAEs across treatments were UTIs (range: 0.7-5.7 %), neck pain (range: 3.7-9.1 %), headache (range: 2.9-6.5 %), and migraine (range: 2.5-6.4 %). There was no apparent trend between TEAE incidence and treatment intervals nor cumulative 3-month dose categories for multiple indications. No patients were determined to have lack of effect based on clinical objective measurement. OnabotA showed a safety profile with no new signals in patients treated concomitantly for ≥2 therapeutic indications over repeat treatments up to 2 years. TEAEs across treatment periods were commonly related to the site of injection and were consistent with those previously reported for individual indications.

Systemic mastocytosis is a rare condition caused by the accumulation of abnormal mast cells (MC) in various organs, including the bone. The diagnosis of mastocytosis is sometimes challenging because of the incidence rate, the heterogeneity of clinical manifestations, and the varying sensitivity of diagnostic tools. While mastocytosis is an uncommon cause of osteoporosis, conversely, systemic mastocytosis (SM) is often associated with bone loss, resulting in low bone mineral density (osteopenia or osteoporosis) and fractures, particularly vertebral fractures. SM must be ruled out in young patients with fragility fractures, mainly vertebral fracture, or unexplained low bone mineral density accompanied by suspected SM symptoms or signs. Other bone manifestations of SM include bone pain, osteolytic lesions, and even osteosclerosis. The putative mechanisms of bone loss and damage in SM include the secretion of vasoactive mediators and inflammatory markers, bone mediators released from bone cells (osteoblast, osteoclast, and osteocyte) such as RANKL, OPG, sclerostin, and DKK1, and neoplastic infiltration of MCs. Usually, early diagnosis with appropriate therapeutic intervention can impact the outcome of this disease and its skeletal-related complications. Fracture prediction can be improved by considering risk factors and using bone mineral density, FRAX, and TBS values. High-resolution peripheral quantitative CT may not be feasible but provides more information. The first step is the detection of high-risk patients in SM by recognizing the risk factors for fragility fractures such as older age, male sex, lower hip BMD, increased mast cell mass, or KIT mutation in bone biopsies, and then estimating the risk of SM progression in order to determine the best type of medication for bone loss mastocytosis and for osteoporosis. The current medications for the treatment of mastocytosis itself include anti-inflammatory or mast cell stabilizers (ketotifen, cromolyn sodium, antihistamines, leukotriene antagonists, and anti-IgE monoclonal antibody). Anti-osteoporosis medications (bisphosphonates, denosumab, and teriparatide) and cytoreductive agents (interferon, chemotherapeutic agents, or tyrosine kinase inhibitors) are also used. Although controlling the underlying disease is usually most effective, the benefits and risks of each therapeutic approach should be balanced if needed.

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.