Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products. OBJECTIVE: We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity. METHODS: We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL. RESULTS: In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth. IMPACT STATEMENT: In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.

Anti-NMDA encephalitis secondary to an ovarian teratoma presenting as altered mental status in a 32-year-old woman: A case report.

NMDA-R encephalitis is an autoimmune encephalitis that is known to be associated with ovarian teratomas. Eighty to 100 % of patients initially present with neuropsychiatric symptoms. Early recognition and intervention are critical to management and prognosis. This case demonstrates non-specific presenting symptoms of NMDA-R encephalitis. A 32-year-old woman presented to the emergency room with headache, nausea, vomiting, and photophobia. She was discharged with probable aseptic meningitis. Eight days later, she represented with delusional thought content, perseverative speech, and bizarre behavior. Cerebrospinal fluid studies showed elevated protein and mild pleocytosis. A computed tomography scan with contrast showed a 35-mm complex cystic lesion in the right adnexa, which was resected. Confirmatory pathology showed a mature cystic teratoma. Paraneoplastic panel later resulted positive for NMDA-R encephalitis. The patient was treated with methylprednisolone, IVIG, plasmapheresis, and rituximab. The clinical course was complicated by a hypersensitivity reaction to rituximab, non-convulsive status epilepticus requiring intubation, dysphagia requiring a PEG placement, a rectal ulcer causing acute blood loss anemia requiring multiple blood transfusions, bilateral hearing loss, and a left lung pneumothorax. The patient's mood, cognition, and motor function were favorably improving 19 months after diagnosis. This case illustrates presenting signs of NMDA-R encephalitis in a young woman as headache and altered mental status followed by psychosis and epilepsy. Treatment should involve a multidisciplinary team and be individualized and escalated in patients with worsening clinical status refractory to first-line therapy. Further research is warranted to understand the optimal treatment strategy for this disease.

Study protocol for the implementation of Centering Patients with Fibroids, a novel group education and empowerment program for patients with symptomatic uterine fibroids.

BACKGROUND: Black women and people with uteri have utilized collectivistic and relational practices to improve health outcomes in the face of medical racism and discrimination for decades. However, there remains a need for interventions to improve outcomes of uterine fibroids, a condition that disproportionately impacts Black people with uteri. Leveraging personalized approaches alongside evidence that demonstrates the positive impact of social and peer support on health outcomes, we adapted from CenteringPregnancy, an evidence based group prenatal care intervention, for the education and empowerment of patients with uterine fibroids. METHODS: The present report provides  an overview of the study design and planned implementation of CPWF in cohorts at Boston Medical Center and Emory University / Grady Memorial Hospital. After receiving training from the Centering Healthcare Institute (CHI), we adapted the 10-session CenteringPregnancy curriculum to an 8-session hybrid group intervention called Centering Patients with Fibroids (CPWF). The study began in 2022 with planned recruitment of six cohorts of 10-12 participants at each institution. We will conduct a mixed methods evaluation of the program using validated survey tools and qualitative methods, including focus groups and 1:1 interviews. DISCUSSION: To date, we have successfully recruited 4 cohorts at Boston Medical Center and are actively implementing BMC Cohort 5 and the first cohort at Emory University / Grady Memorial Hospital. Evaluation of the program is forthcoming.

Fibroids are non-cancerous smooth muscle tumors that disproportionate impact black women and gender expansive people. Our team adapted CenteringPregnancy, a group based model of prenatal care, to an education and empowerment program for peple with fibroids called Centering Patients with Fibroids (CPWF). This paper describes the development and implemation of the program at two academic hospitals serving diverse patients in Boston, Massachusetts and Atlanta, Georgia. To evaluate the successes and challenges of the program, we ask participants to complete surveys to learn more about their experience with having fibroids and also invite them to group feedback sessions or focus groups. We also interview other healthcare providers, team members, and hospital leadership on their knowledge and thoughts about the program. We hope to use the feedback to improve the program and make it available to more people across the country.

A prospective ultrasound study of cigarette smoking and uterine leiomyomata incidence and growth.

BACKGROUND: Uterine leiomyomata (fibroids) are common, benign neoplasms that contribute substantially to gynecologic morbidity. Some existing epidemiologic studies indicate that cigarette smoking is associated with lower uterine leiomyomata risk. However, no prospective studies have systematically screened an entire study population for uterine leiomyomata using transvaginal ultrasound or evaluated the association between cigarette smoking and uterine leiomyomata growth. OBJECTIVE: This study aimed to examine the association between cigarette smoking and uterine leiomyomata incidence and growth in a prospective ultrasound study. STUDY DESIGN: We enrolled 1693 residents from the Detroit metropolitan area into the Study of Environment, Lifestyle, and Fibroids during 2010 to 2012. Eligible participants were aged 23 to 34 years, had an intact uterus but no previous diagnosis of uterine leiomyomata, and self-identified as Black or African American. We invited participants to complete a baseline visit and 4 follow-up visits over approximately 10 years. At each visit, we used transvaginal ultrasound to assess uterine leiomyomata incidence and growth. Participants provided extensive self-reported data throughout follow-up including exposures to active and passive cigarette smoking in adulthood. We excluded participants who did not return for any follow-up visits (n=76; 4%). We fit Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals for the association between time-varying smoking history and incidence rates of uterine leiomyomata. We fit linear mixed models to estimate the percentage difference and 95% confidence intervals for the association between smoking history and uterine leiomyomata growth. We adjusted for sociodemographic, lifestyle, and reproductive factors. We interpreted our results based on magnitude and precision rather than binary significance testing. RESULTS: Among 1252 participants without ultrasound evidence of uterine leiomyomata at baseline, uterine leiomyomata were detected in 394 participants (31%) during follow-up. Current cigarette smoking was associated with a lower uterine leiomyomata incidence rate (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Associations were stronger among participants who had smoked for longer durations (≥15 years vs never: hazard ratio, 0.49; 95% confidence interval, 0.25-0.95). The hazard ratio for former smokers was 0.78 (95% confidence interval, 0.50-1.20). Among never smokers, the hazard ratio for current passive smoke exposure was 0.84 (95% confidence interval, 0.65-1.07). Uterine leiomyomata growth was not appreciably associated with current (percent difference, -3%; 95% confidence interval, -13% to 8%) or former (percent difference, -9%; 95% confidence interval, -22% to 6%) smoking. CONCLUSION: We provide evidence from a prospective ultrasound study that cigarette smoking is associated with lower uterine leiomyomata incidence.

Geographic Variation in Obesity at the State Level in the All of Us Research Program.

INTRODUCTION: National obesity prevention strategies may benefit from precision health approaches involving diverse participants in population health studies. We used cohort data from the National Institutes of Health All of Us Research Program (All of Us) Researcher Workbench to estimate population-level obesity prevalence. METHODS: To estimate state-level obesity prevalence we used data from physical measurements made during All of Us enrollment visits and data from participant electronic health records (EHRs) where available. Prevalence estimates were calculated and mapped by state for 2 categories of body mass index (BMI) (kg/m2): obesity (BMI >30) and severe obesity (BMI >35). We calculated and mapped prevalence by state, excluding states with fewer than 100 All of Us participants. RESULTS: Data on height and weight were available for 244,504 All of Us participants from 33 states, and corresponding EHR data were available for 88,840 of these participants. The median and IQR of BMI taken from physical measurements data was 28.4 (24.4- 33.7) and 28.5 (24.5-33.6) from EHR data, where available. Overall obesity prevalence based on physical measurements data was 41.5% (95% CI, 41.3%-41.7%); prevalence of severe obesity was 20.7% (95% CI, 20.6-20.9), with large geographic variations observed across states. Prevalence estimates from states with greater numbers of All of Us participants were more similar to national population-based estimates than states with fewer participants. CONCLUSION: All of Us participants had a high prevalence of obesity, with state-level geographic variation mirroring national trends. The diversity among All of Us participants may support future investigations on obesity prevention and treatment in diverse populations.

Hypertension prevalence in the All of Us Research Program among groups traditionally underrepresented in medical research.

The All of Us Research Program was designed to enable broad-based precision medicine research in a cohort of unprecedented scale and diversity. Hypertension (HTN) is a major public health concern. The validity of HTN data and definition of hypertension cases in the All of Us (AoU) Research Program for use in rule-based algorithms is unknown. In this cross-sectional, population-based study, we compare HTN prevalence in the AoU Research Program to HTN prevalence in the 2015-2016 National Health and Nutrition Examination Survey (NHANES). We used AoU baseline data from patient (age ≥ 18) measurements (PM), surveys, and electronic health record (EHR) blood pressure measurements. We retrospectively examined the prevalence of HTN in the EHR cohort using Systemized Nomenclature of Medicine (SNOMED) codes and blood pressure medications recorded in the EHR. We defined HTN as the participant having at least 2 HTN diagnosis/billing codes on separate dates in the EHR data AND at least one HTN medication. We calculated an age-standardized HTN prevalence according to the age distribution of the U.S. Census, using 3 groups (18-39, 40-59, and ≥ 60). Among the 185,770 participants enrolled in the AoU Cohort (mean age at enrollment = 51.2 years) available in a Researcher Workbench as of October 2019, EHR data was available for at least one SNOMED code from 112,805 participants, medications for 104,230 participants, and 103,490 participants had both medication and SNOMED data. The total number of persons with SNOMED codes on at least two distinct dates and at least one antihypertensive medication was 33,310 for a crude prevalence of HTN of 32.2%. AoU age-adjusted HTN prevalence was 27.9% using 3 groups compared to 29.6% in NHANES. The AoU cohort is a growing source of diverse longitudinal data to study hypertension nationwide and develop precision rule-based algorithms for use in hypertension treatment and prevention research. The prevalence of hypertension in this cohort is similar to that in prior population-based surveys.

Vascular repairs in gynecologic operations are uncommon but predict major morbidity and mortality.

OBJECTIVE: Gynecologic surgery has potential for adjunct vascular interventions, given the proximity of major intra-abdominal and pelvic blood vessels. Our goal was to determine contemporary incidence, associations, and outcomes of vascular repairs in gynecologic operations. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (2005-2017) was queried for patients undergoing elective gynecologic operations. Vascular repairs were performed concurrently or during reoperation. Univariable and multivariable analyses evaluated associations with vascular repairs and 30-day morbidity. RESULTS: A total of 201,224 gynecologic operations were identified: hysterectomy (88.3%), myomectomy (5.9%), adnexal surgery (3.5%), vulvovaginectomy/other (1.1%), nonadnexal tumor or cyst excision (0.5%), ectopic pregnancy treatment (0.4%), and pelvic lymphadenectomy (0.3%). There were 187 vascular repairs in 176 (0.09%) patients. Repairs were typically concurrent (89.8%) and most commonly included open abdominal blood vessel repair (51.8%), major abdominal artery ligation (25%), vena cava reconstruction/ligation (6%), common iliac vein ligation (4.2%), and aorta/great vessel repair (4.2%). A minority were performed endovascularly (1.7%). Patients undergoing vascular repairs were older (56 vs 46 years), were more likely to have an open vs minimally invasive/vaginal operation (71.6% vs 28.4%), and were more likely to have a hysterectomy (85.2%; P < .001 for all). In multivariable analysis, vascular repairs were observed more often with hysterectomy (odds ratio [OR]; 7.63, 95% confidence interval [CI], 2.28-25.55; P = .001) and open vs minimally invasive/vaginal operations (OR, 5.24; 95% CI, 2.64-10.42; P < .001). Vascular repairs were also more common for patients with malignant disease (OR, 2.84; 95% CI, 1.78-4.53; P < .001), patients assigned to American Society of Anesthesiologists class 3 or class 4 (OR, 1.85; CI, 1.36-2.53; P = .002), and patients without obesity (OR, 1.45; 95% CI, 1.08-1.96; P = .014). Vascular repairs independently predicted major morbidity and mortality (OR, 7.26; 95% CI, 5.26-10.03; P < .001) after adjustment for open operative approach, American Society of Anesthesiologists class 3 or class 4, and hysterectomy. CONCLUSIONS: Whereas vascular repairs during gynecologic operations are rare, they are associated with morbidity and mortality. These findings provide an evidence base for risk assessment and informed consent.

Morcellation complications: From direct trauma to inoculation.

Morcellation is the fragmentation of tissue to facilitate removal of the specimen through small incision in minimally invasive surgery. This technique is not unique to gynecology and is used in general surgery with the goal of improved surgical outcomes including decreased pain, cost, hospital length of stay, and rapid return to normal activities and work. Gynecologic laparoscopic power morcellation (LPM) has come under increased scrutiny over the last 2 years due to widespread attention to a known but rare complication, an unanticipated dissemination of malignancy, namely occult uterine leiomyosarcoma. This chapter focuses on complications associated with gynecologic tissue morcellation from inoculation of benign or malignant tissue fragments within the peritoneal cavity and direct trauma from morcellation techniques. We also include a review of the various morcellation techniques from knife to electrical and the use of intraperitoneal specimen containment systems.