High-risk Clinic Research Articles

The genetic landscape of Lynch syndrome in the Israeli population.

Deciphering the spectrum and founder disease-causing variants (DCVs) in specific populations can shape and facilitate the diagnostic process of Lynch Syndrome (LS). The aim of this report was to comprehensively update on the genetic landscape of LS in the ethnically diverse Israeli-Jewish population. The cohort included 1080 carriers from 588 families; some from underrepresented, understudied Israeli ethnic groups recruited from 8 genetic institutes and high-risk clinics throughout the country. Variant classification was performed according to the American College of Medical Genetics criteria. A total of 157 DCVs were identified, 12 are reported here for the first time, and 9 reclassified. MSH2 DCVs were identified in 286 families (49%). Most DCVs (125/157, 80%) were noted in one or two families only. Sixteen DCVs, each detected in ≥ 5 families, and accounted for LS in 378/588 (64%) families. Constitutional mismatch repair deficiency (CMMRD) was diagnosed in 7 families. Twenty-five carriers (2.3%) had an additional DCV or risk alleles in another cancer susceptibility gene. In conclusion, MMR gene variant distribution in Israel is diverse. MSH2 is most commonly mutated due to founder DCVs. Though the 16 prevalent LS-associated DCVs were frequently detected in our cohort, none of them is frequently reported in the general population. These data should facilitate variant interpretation, spouse and cascade testing.

Review article: Prevention of inflammatory bowel disease-The path forward.

The possibility of preventing inflammatory bowel disease (IBD) is becoming more plausible due to advances in understanding preclinical disease and successful prevention trials in other immune-mediated diseases, such as type 1 diabetes and rheumatoid arthritis. However, before that possibility becomes reality, several efforts need to occur in parallel and in a coordinated way. To propose some critical steps necessary for advancing the field of IBD prediction and prevention. We reviewed the current literature to identify the necessary steps toward a preventive strategy for IBD. The first step should determine the most robust predictive biomarkers and validate them across independent cohorts, creating a multidimensional predictive tool. The second step is to gain a better understanding of the preferences of first-degree relatives and people at risk for IBD, informing the implementation of screening and preventive strategies. Third, these efforts should contribute to the development of high-risk clinics and establish the necessary networks for disease prevention trials. Advancing the field of IBD prediction and prevention will require a multifaceted approach, integrating biomarker discovery, understanding patient preferences, and establishing infrastructure for a collaborative network to support the practical implementation of IBD prevention strategies.

A Survey of Obstetric Anaesthesia Services and Practices in the United Kingdom.

Background Variability in obstetric anaesthetia practice and care delivered within the UK is under-explored. The ObsQoR study explored structures, processes, and outcomes of obstetric anaesthesia in 107 hospitals within the UK's National Health Service, and the results of the hospital-level survey are reported here. Methods Hospitals were surveyed to assess obstetric anaesthesia provision, practice, and care delivery. Questions explored staffing, service provision and training, facilities present, clinical practices, outcome measurement, and key indicators of quality in obstetric anaesthesia. Results We received responses from 106 participating hospitals, representing 69% of all UK obstetric units. One hundred (94%) hospitals had a dedicated consultant obstetric anaesthetist within working hours, with 27 (25%) of hospitals' duty anaesthetists having additional clinical responsibilities outside the care of obstetric patients outside of working hours. Around 102 hospitals (98%) offer multidisciplinary team training, of which 95 (93%) use a simulation-based method. Dedicated high-risk antenatal clinics were present in 50 (47%) hospitals. The majority of hospitals provide written patient information in multiple languages for discussing obstetric anaesthesia options (77, 82%). Seventy-three hospitals (69%) use point-of-care testing to estimate haemoglobin concentration. Labour epidural analgesia is most commonly delivered via patient-controlled epidural analgesia in 80 (76%) hospitals, and the incidence of post-dural puncture headaches was recorded by 80 (76%) hospitals. Conclusions These results demonstrate variation in the provision of staffing, facilities, clinical practices, and outcome measurements across the UK. To deliver safe and equitable care across the UK, there needs to be standardisation of anaesthetic peripartum care based on national recommendations and the benchmarking and measurement of appropriate markers of quality.

Abstract B025: Surveillance outcome in individuals at high risk of pancreatic cancer

Abstract INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate. PDAC surveillance is recommended in high-risk individuals (HRIs) with strong PDAC family history or a pathogenic germline variant (PGV) in a PDAC susceptibility gene. We aimed to explore a potential correlation between genetic status, extent of family history, pancreatic findings, and surveillance implications in heterogeneous PDAC HRIs. METHODS: from January 2015 up to date, a total of 340 HRIs from 291 families visited our pancreatic cancer high-risk clinic. Surveillance included annual clinic visits, EUS/MRI imaging, genetic and laboratory blood testing. Participants completed a questionnaire that included personal and familial medical history, dietary habits, daily activities with emphasis on smoking habits, alcohol use, and physical activity. RESULTS: Our cohort was divided into 3 groups: familial pancreatic cancer that include individuals with family history of 2 or more first degree family (FDR) with PDAC (FPC; 96 individuals), familial non-FPC, families with at least 2 biological relatives with PDAC and not meeting FPC criteria, (119 individuals), and hereditary pancreatic cancer (PC), individuals with PGV in a PC susceptibility gene and a family member with PDAC carrying the same PGV (124 individuals). The cohort average age at first visit was 54 years with 44% male and 56% female ratio. Seventy percent of the cohort was of Jewish Ashkenazi decent. Genetic testing was performed in several steps, first BRCA1/2 founder mutations was performed in all individuals followed by genetic panels and whole exome sequencing (WES). PGVs were detected in 36.4% of all families. There was no significant difference in the genetic finding between the FPC and non-FPC groups (11% and 9.6% respectively). Of the study cohort 35% were screened by EUS and 8% by MRI/MRCP. Pancreatic lesions detected included 11 cases of new PDAC (3.2%), 69 cystic lesions (20.3%), 43 cases early chronic pancreatitis (12.6%) and 11 cases of main pancreatic duct dilation (3.2%). To better understand the risk of PDAC development in HRIs we recently added a novel cell-free chromatin blood test for early cancer detection (in collaboration with SENSEERA, Israel) and compared it to EUS imaging results. The test provides multidimensional epigenetic information that sheds light on the identity and the transcriptional state of the cells that are dying in the body of the patient. Our preliminary results show nice separation between the healthy control and PC groups. PC HRIs show slight increase in score compared to the general population while individuals with worrisome features show substantial increase compared to HRIs with no EUS findings. DISCUSSION: Surveillance seems effective for detection of early-stage PDAC and precursor lesions. However, screening strategy can be improved by adding newer modalities like chromatin-based tests that might help to further define the risk of cancer development in HRIs. Citation Format: Merav Ben Yehoyada, Erez Scapa, Oren Shibolet, Guy Rosner. Surveillance outcome in individuals at high risk of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B025.

Risk-reducing surgeries for breast cancer in Brazilian patients undergoing multigene germline panel: impact of results on decision making.

To assess the behavior change of high-risk breast cancer patients regarding the intention to undergo risk-reducing mastectomies (RRM) before and after genetic testing results and to identify the main influencing factors in decision-making. Prospective cohort study conducted between November 2021 and October 2022 with women under follow-up at the high-risk outpatient clinic of the State University of Campinas (UNICAMP). Patients were referred for genetic testing, followed by counseling according to the test result. A total of 373 women were included. In the pre-genetic testing analysis, 54.1% of patients intended to undergo RRMs. After testing, 42.2% opted for the procedure. Behavior change occurred in 26.2%, mainly from "yes" to "no/don't know" (72,6%) (p < 0.001). The genetic test result was positive (LPV or PV) in 29.7% of patients. Among the 90 patients with positive results, 62 (68.9%) agreed to RRM, while 22 (24.4%) remained unwilling to accept RRM, regardless of the positive test. Significant influencing factors for behavior change pre- and post-genetic testing (in favor of surgery) in multivariate analysis were: positive genetic test result (OR 2.94, p < 0.001), personal cancer history (OR 2.7, p = 0.008), and ages between 40 and 49years (OR 2.07, p = 0.008) and ≥ 50years (OR 3.47, p < 0.001). In a Brazilian population at high-risk for breast cancer and users of the public health system, it was observed that most desired RRM, however, when genetic testing and counseling were performed, behavior change was observed, especially when the result was positive.

Evaluation of Screening Results for Vancomycin-Resistant Enterococci: Three-Year Surveillance.

Enterococci are facultative anaerobic, binary, or chained Gram-positive cocci. The gastrointestinal colonization of hospitalized patients is the most important reservoir of vancomycin-resistant enterococci. We aimed to evaluate retrospectively the screening results of vancomycin-resistant enterococci, studied by the simultaneous (real-time) polymerase chain reaction method on rectal swabs of adult and pediatric patients hospitalized in our hospital in 2019-2021. Adult and pediatric patients were included in our study between Jan 2019 and Dec 2021. The results of vancomycin-resistant enterococci, studied with the real-time polymerase chain reaction method from rectal swabs sent from intensive care units and services, were analyzed retrospectively. Isolation of the samples was performed using the Fluorion VRE QLP 1.0 real-time polymerase chain reaction kit (Iontek, Turkey), and detection was performed with the Fluorion Detection System (Iontek, Turkey) real-time polymerase chain reaction device. Overall, 31,725 patients were included in our study. When evaluated in order of years, in 2019, 379 (7%) of 5,389 adults, 322 (7.4%) of 4,003 children, 234 (5.5%) of 4,185 adults in 2020, 157 (2.4%) of 6,499 children, and in 2021, vancomycin-resistant enterococci were detected in 469 (7.5%) of 6,232 adults and 224 (4.1%) of 5,417 children. The prevalence of vancomycin-resistant enterococci is greater in adults, particularly in intensive care units, compared to children. Infection control precautions and training be augmented in high-risk clinics, while the unnecessary utilization of glycopeptides should be limited.

The role of Thompson score of term newborns in predicting neuromotor outcome at 1 year of age

Background: The mortality rate is approximately 20% and the frequency of neurodevelopmental sequelae in surviving newborns is approximately 30% in perinatal asphyxia; hypoxic-ischemic encephalopathy (HIE) is brain dysfunction due to lack of oxygen and blood supply to the brain. Aims and Objectives: This study was conducted to predict the pattern of neuromotor outcome as early as 3 months using Hammersmith Infant Neurological Examination (HINE) in term hypoxic babies and its relation with the Thompson score (HIE score). Materials and Methods: One-hundred twenty four term newborns with hypoxic babies were admitted to the neonatal care unit from January 2021 to August 2021. Thompson scoring was done on admission and subsequently reviewed. Discharged babies were followed up at 3 months, 6 months, and 1 year of age. A neurological examination (HINE) was done in this high-risk follow-up clinic. Maximum Thompson score was correlated with neurological score at various months. The earliest predictability of neurological examination was done at 3 months and was correlated with the neurological examination done at 12 months. Results: The correlation between the Thompson score and the 3-month score is −0.65 indicating a strong negative association between the two measurements. The correlation between 3 months and 6 months and 1-year neurological scores was moderately associated with each other. Conclusion: The maximum Thompson score was significantly higher in the mortality group compared to the discharged group. Thompson score has a significant correlation with the 3, 6, and 12-month neurological scores examined by HINE. The 3-month neurological outcome has a very significant correlation with the 1-year outcome.

Evaluation of person-centered interventions to eliminate perinatal HIV transmission in Kisumu County, Kenya: A repeated cross-sectional study using aggregated registry data.

Following a decline in perinatal HIV transmission from 20% to 10% between 2010 and 2017 in Kenya, rates have since plateaued with an estimated 8% transmission rate in 2021. Between October 2016 and September 2021, Family AIDS Care & Education Services (FACES) supported HIV care and treatment services across 61 facilities in Kisumu County, Kenya with an emphasis on service strengthening for pregnant and postpartum women living with HIV to reduce perinatal HIV transmission. This included rigorous implementation of national HIV guidelines and implementation of 3 locally adapted evidence-based interventions targeted to the unique needs of women and their infants. We examined whether these person-centered program enhancements were associated with changes in perinatal HIV transmission at FACES-supported sites over time. We conducted a repeated cross-sectional study of annually aggregated routinely collected documentation of perinatal HIV transmission risk through the end of breastfeeding at FACES-supported facilities between October 2016 and September 2021. Data included 12,599 women living with HIV with baseline antenatal care metrics, and, a separate data set of 11,879 mother-infant pairs who were followed from birth through the end of breastfeeding (overlapping with those in antenatal care 2 years prior). FACES implemented 3 interventions for pregnant and postpartum women living with HIV in 2019: (1) high-risk clinics; (2) case management; and (3) a mobile app to support treatment engagement. Our primary outcome was infant HIV acquisition by the end of breastfeeding (18 to 24 months). We compared infant HIV acquisition risk in the final year of the FACES program (2021) to the year before intervention scale-up and following implementation of the "Treat All" policy (2018). Mother-infant pair loss to follow-up was a secondary outcome. Program data were aggregated by year and site, thus in multivariable regression, we adjusted for site-level characteristics, including facility type, urban versus rural, number of women with HIV in antenatal care each year, and the proportion among them under 25 years of age. Between October 2016 and September 2021, 81,172 pregnant women received HIV testing at the initiation of antenatal care, among whom 12,599 (15.5%) were living with HIV, with little variation in HIV prevalence over time. The risk of infant HIV acquisition by 24 months of age declined from 4.9% (101/2,072) in 2018 to 2.2% (48/2,156) in 2021 (adjusted risk difference -2.6% [95% confidence interval (CI): -3.7, -1.6]; p < 0.001). Loss to follow-up declined from 9.9% (253/2,556) in 2018 to 2.5% (59/2,393) in 2021 (risk difference -7.5% [95% CI: -8.8, -6.2]; p < 0.001). During the same period, UNAIDS estimated rates of perinatal transmission in the broader Nyanza region and in Kenya as a whole did not decline. The main limitation of this study is that we lacked a comparable control group. These findings suggest that implementation of person-centered interventions was associated with significant declines in perinatal HIV transmission and loss to follow-up of pregnant and postpartum women.

Survival benefit associated with screening of patients at elevated risk for pancreatic cancer.

All patients enrolled in screening at a High-Risk Pancreatic Cancer Clinic (HRC) from July 2013 to June 2020 were identified from a prospectively maintained institutional database and compared to patients evaluated at a Surgical Oncology Clinic (SOC) at the same institution during the same period. Clinical outcomes of patients selected for surgical resection, particularly clinicopathologic stage and overall survival, were compared. Among 826 HRC patients followed for a median (IQR) of 2.3 (0.8-4.2) years, 128 were selected for surgical resection and compared to 402 SOC patients selected for resection. Overall survival was significantly longer among HRC patients (median survival: not reached vs. 2.6 years, p < 0.001). Among 31 HRC and 217 SOC patients with a diagnosis of pancreatic ductal adenocarcinoma(PDAC), the majority of HRC patients were diagnosed with stage 0 disease (carcinoma in situ), while the majority of SOC patients were diagnosed with stage II disease (p < 0.001). Overall survival after resection of invasive PDAC was also significantly longer among HRC patients compared to SOC patients (median survival 5.5 vs. 1.6 years, p = 0.002). Patients at increased risk for PDAC and followed with guideline-based screening exhibited downstaging of disease and improved survival from PDAC in comparison to patients who were not screened.

"Understanding knowledge and attitudes regarding hypertensive disorders of pregnancy among expectant women in Brunei Darussalam: A nationwide study"

BackgroundThe primary cause of maternal and fetal mortality due to hypertensive disorders in pregnancy is delays in accessing healthcare services. These delays are often attributed to insufficient knowledge, attitudes at the time of diagnosis, and a lack of awareness regarding the condition, including its critical warning signs and symptoms. AimTo evaluate pregnant women's initial knowledge and attitudes upon receiving their first diagnosis of hypertensive disorders of pregnancy. MethodsA cross-sectional quantitative design was used to assess the knowledge and views of 216 expectant mothers on hypertensive disorders of pregnancy (HDP) across three high-risk clinics in Brunei Darussalam. Participants were selected through convenience sampling. Data were collected using a bilingual self-administered questionnaire, adapted from a validated instrument. Descriptive statistics and inferential analyses, including t-tests, One-Way ANOVA, and multiple regression, were conducted using SPSS (Version 23). ResultsAmong 216 participants, 69 % demonstrated good knowledge of hypertensive disorders during pregnancy (p < 0.001). Despite positive attitudes towards seeking medical help (p < 0.001), 69 % initially opted for home remedies, and 50 % avoided hospitals unless necessary, leading to delays in healthcare-seeking behaviour. The findings highlight the need for targeted health campaigns to bridge the gap between knowledge and practice, ensuring timely medical intervention for hypertensive disorders during pregnancy. ConclusionThe study reveals significant knowledge gaps and attitudes contributing to delayed healthcare-seeking behaviours. Targeted health campaigns and culturally sensitive educational programs are essential to improve timely medical interventions and maternal outcomes in Brunei Darussalam.

Tetralogy of Fallot in adults.

Following surgical repair in infancy, a high proportion of children born with tetralogy of Fallot are surviving into adulthood, and it is important that these patients are monitored by an adult congenital heart disease specialist for problems and complications that can occur in the adult patient. To provide an overview on the management of adult patients with repaired tetralogy of Fallot and emphasise the need for specialist follow-up. Following surgical repair of tetralogy of Fallot, it is important to have lifelong surveillance in adulthood for complications such as pulmonary valve dysfunction. Modern imaging modalities have helped with monitoring and the early detection of problems. Cardiac surgery has been refined over the years, leading to improved longevity. Over the past 23 years, percutaneous interventions have been developed to deal with valve complications and the results have been promising. Healthy behaviour, such as regular exercise, and behaviours to minimise the risk of endocarditis should be encouraged. Regular follow-up with an adult congenital heart disease specialist is important. Patients wishing to undertake a pregnancy should be supervised through a high-risk pregnancy clinic.

The Microbial Diversity and Antimicrobial Susceptibility Profile Underlying Diabetic Foot Osteomyelitis: A Retrospective Study Conducted in North Queensland, Australia.

Diabetic foot osteomyelitis (DFO) commonly occurs secondary to ulcerations of the skin. Empirical antibiotic agents are a key element of treatment and their use is dependent on local knowledge of the microbial spectrum of diabetic foot infections. This study aimed to retrospectively analyze the local microbiological profile, including bacterial culture/sensitivity results of DFO, and compare findings with literature. This study also aimed to review the concordance of microbiology results with national guidelines for the future treatment of DFO. A retrospective review of clinical records was performed on patients who presented to the high-risk foot clinic, Townsville University Hospital, between 2018 and 2022. All patients older than 18 years and diagnosed with DFO were included. Our exclusion criteria included all other foot presentations, including trauma, vasculitis, and neoplasms. On the basis of the inclusion and exclusion criteria, 124 patients with DFO were selected. Most patients in the cohort were males (70.2%), non-Indigenous (68.5%), aged 50-69 years (55.6%), and with elevated HbA1c levels (>8.6). Chronic kidney disease (39.5%) and ischemic heart disease (41.9%) were common comorbidities. Of the pertinent microbial results, Staphylococcus aureus (~76%) was the most commonly isolated Gram-positive organism. Gram-positive bacteria were significantly increased in the elderly population with DFO (P < .05). All methicillin-resistant S aureus isolates were vancomycin- and cotrimoxazole-sensitive. Pseudomonas aeruginosa was the predominant Gram-negative organism isolated (39.3%). P aeruginosa exhibited low sensitivity to ciprofloxacin. This study has enhanced our understanding of the various microbial species underlying DFO at our center and may be generalizable. Level IV, retrospective case series.

A Review of High-Risk Pregnancy Complications in the Resident Clinic

Introduction: A high risk status can develop during a patient’s pregnancy or can be present from conception. These include maternal pre-existing conditions such as hypertension, diabetes, infection such as HIV, and obesity. Fetal complications such as anomaly or multiple gestation also constitute high risk pregnancies. The Corewell Health East Dearborn resident high risk clinic helps to manage these patients’ pregnancies and deliveries. This study aims to analyze the current complications and delivery outcomes of pregnancies from this clinic. Methods: The prenatal care data and pregnancy outcomes from patients in our high-risk resident clinic was collected from Jan 1st 2023 to Jan 1st 2024. The prenatal care data was analyzed for maternal and fetal complications along with delivery outcomes. Results: During the year 2023, 100 patients delivered from the high-risk clinic. Fetal complications were found in 32% of these deliveries. These included 12% twin gestation, 14% growth restriction, 6% fetal anomalies. Maternal complications included 27% with chronic hypertension, 23% with prior cesarean section, 27% with a BMI of 40 or higher, 10% cardiac complications, 4% pre-existing renal complications, 26% with pre-existing diabetes, 3% wtih HIV, and 6% with polysubstance use. The deliveries included 62% cesarean sections and 34% vaginal deliveries. Discussion: The results from our cross-sectional study revealed a high rate of maternal and fetal complications among patients from our high-risk clinic when compared to national averages. There was a high cesarean section rate for these patients. Conclusions: This study allowed us to better understand the patient population that receives care through the resident high-risk clinic. Future studies can explore how to decrease the cesarean section rate.

Adherence to cancer screening for patients with Li-Fraumeni syndrome: A report on our experience at Fred Hutchinson Cancer Center.

e22553 Background: Li-Fraumeni syndrome (LFS) is a high-risk cancer predisposition syndrome where patients are at risk of developing multiple primary cancers, synchronous, and metachronous cancers in their lifetimes. Patients with LFS often serve as their own advocates to request and receive appropriate cancer screening as few clinicians have experience in caring for them and few clinics are adequately staffed to provide complex cancer screening coordination. Methods: Fred Hutchinson Cancer Center (Fred Hutch) is a large academic cancer care center associated with the University of Washington. In July 2020, Fred Hutch's clinical cancer genetic service launched a high-risk surveillance clinic for patients with hereditary cancer syndromes requiring services from multiple specialties. Our clinic has since helped patients with LFS receive coordinated cancer screening. Here we report on adherence to the Toronto protocol by reviewing patient demographic, cancer history and family history, and genetic records. Furthermore, we report on the number of visits, types of screening, and cancer diagnoses patients with LFS received since enrolling in the high-risk clinic. Results: A total of 112 patients with LFS were seen in the high-risk surveillance clinic between July 2020 and December 2023. Of these patients’ paths reviewed so far, 73 patients established with the clinic and received blood work and/or MRI imaging scans, and 42 were seen in at least one follow up visit. 2 patients with LFS were diagnosed with one or more new cancer diagnosis since enrollment, both have completed treatment, and both are without evidence of disease as of February 2024. Conclusions: The high-risk surveillance clinic was promptly utilized by patients with LFS for coordination of their complex cancer screening needs and to guide their next steps when triaging symptoms and concerns. While the clinic addresses a gap in cancer screening coordination, patients with LFS need wrap around care close to where they live which is difficult to accomplish in the Pacific Northwest.

Evaluation of multidisciplinary high-risk pregnancy clinic for myelomeningocele

IntroductionA cross-sectional study retrospectively evaluating the perceived usefulness of attending a multi-disciplinary, roundtable, educational prenatal clinic for mothers expecting children with myelomeningocele is presented.MethodsMothers who currently have children with SB completed a survey which evaluated their overall preparedness, spina bifida education, delivery plans, surgical expectations, and expectations in terms of quality of life and development. Open comments were also collected. Statistical analysis was performed to identify differences between those who attended prenatal counseling and those who did not.ResultsApproximately half of these mothers received some form of prenatal SB counseling. Mothers who attended prenatal counseling reported that they felt more informed and prepared throughout their pregnancy, during the delivery of their child and during their initial hospital stay than mothers who did not. They reported that the roundtable discussions were beneficial, and the education they received was useful in helping them form accurate expectations and feel more at ease.ConclusionThis suggests that prenatal counseling and the High-Risk Pregnancy Clinic (HRPC) provides perceived utility to families and mothers and that the HRPC is an effective method of providing prenatal counseling to mothers whose unborn children have been diagnosed with myelomeningocele.

Referral practices and treatment of obstructive sleep apnea in pregnancies with obesity.

Obstructive sleep apnea (OSA) affects maternal and neonatal health during pregnancy. This study aimed to identify characteristics and comorbidities associated with sleep clinic referral in high-risk pregnancies with Body Mass Index (BMI) ≥35kg/m2. Retrospective cohort study for individuals in a high-risk pregnancy clinic at a tertiary Australian hospital from 1 January to 31 December 2020 with BMI≥35kg/m2. The primary outcome measure was sleep clinic referral. Exposure data included multiple comorbidities and formal tools (Epworth Sleepiness Scale and STOP-BANG). Multivariable analysis was used to identify factors associated with referral. Descriptive data on barriers to diagnosis and treatment were collected. Of 161 pregnant individuals, 38.5% were screened using formal tools and 13.7% were referred to sleep clinic. Having STOP-BANG performed was associated with sleep clinic referral (Odds Ratio: 18.04, 95% Confidence Interval:4.5-71.7, p<0.001). No clinical characteristics were associated with the likelihood of performing STOP-BANG. The COVID-19 pandemic was a treatment barrier for three individuals. Current screening practices identify pregnant individuals with the highest pre-test probability of having OSA. Future research should evaluate real-world strategies to improve identification and management in this high-risk population.

MSH3-related adenomatous polyposis in a patient with the negative family history of colorectal polyps

Recently, biallelic MSH3 germline pathogenic/likely pathogenic variants have been recognized as a rare cause of adenomatous polyposis. We present a 49-year-old woman who was admitted to our high-risk colorectal cancer clinic after incidental detection of a biallelic MSH3 (likely) pathogenic variant when tested for the germline (likely) pathogenic variants in hereditary breast and ovarian cancer related genes. The focus of this case report is to describe the genotype and phenotype of our patient with MSH3-related adenomatous polyposis. More than half of the polyps (13/19) were located in the right colon. In addition, benign and malignant extraintestinal lesions may be common as our patient had simple liver and kidney cysts and two basal cell skin carcinomas.

Physical activity among pregnant inpatients and outpatients and associations with anxiety

ObjectivePhysical activity is linked to lower anxiety, but little is known about the association during pregnancy. This is especially important for antepartum inpatients, who are known to have increased anxiety yet may not be able to achieve target levels of physical activity during hospitalization. We compared physical activity metrics between pregnant inpatients and outpatients and explored correlations with anxiety. Materials and MethodsThis was a prospective cohort between 2021 and 2022 of pregnant people aged 18–55 years carrying singleton gestations ≥ 16 weeks. Three exposure groups were matched for gestational age: 1) outpatients from general obstetric clinics; 2) outpatients from high-risk Maternal-Fetal Medicine obstetric clinics; and 3) antepartum inpatients. Participants wore Actigraph GT9X Link accelerometer watches for up to 7 days to measure physical activity. The primary outcome was mean daily step count. Secondary outcomes were metabolic equivalent tasks (METs), hourly kilocalories (kcals), moderate to vigorous physical activity (MVPA) bursts, and anxiety (State-Trait Anxiety Inventory [STAI]). Step counts were compared using multivariable generalized estimating equations adjusting for maternal age, body-mass index, and insurance type as a socioeconomic construct, accounting for within-group clustering by gestational age. Spearman correlations were used to correlate anxiety scores with step counts. Results58 participants were analyzed. Compared to outpatients, inpatients had significantly lower mean daily steps (primary outcome, adjusted beta −2185, 95 % confidence interval [CI] −3146, −1224, p < 0.01), METs (adjusted beta −0.18, 95 % CI −0.23, −0.13, p < 0.01), MVPAs (adjusted beta −38.2, 95 % CI −52.3, −24.1, p < 0.01), and kcals (adjusted beta –222.9, 95 % CI −438.0, −7.8, p = 0.04). Over the course of the week, steps progressively decreased for inpatients (p-interaction 0.01) but not for either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30, p = 0.02). ConclusionWe present antenatal population norms and variance for step counts, metabolic equivalent tasks, moderate to vigorous physical activity bursts, and kcals, as well as correlations with anxiety. Antepartum inpatients had significantly lower physical activity than outpatients, and lower step counts correlated with higher anxiety levels. These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people.

Pilot Study of the FitMoms2B Physical Activity Promotion Program Among Black Women With High-Risk Pregnancies

ObjectiveTo explore the feasibility of recruitment, adherence, and retention and the acceptability of the FitMoms2B physical activity promotion program and study measures among non-Hispanic Black women with high-risk pregnancies. DesignOne-arm pilot feasibility study. SettingA large regional high-risk prenatal clinic in the southeastern United States. ParticipantsNon-Hispanic Black women who had singleton, high-risk pregnancies at 16 to 23 weeks gestation with no contraindications to physical activity (N = 13). MethodWe evaluated the feasibility and acceptability of a multicomponent intervention, which included physical activity coaching, support from a workout partner, and an activity tracker. We also assessed the feasibility of study measures for future trials of the program. ResultsOf 179 patients screened, 20 were eligible, and 13 consented and enrolled (65%). Of the 13 participants, 9 completed data collection at Time Point (T) 1 (16–23 weeks gestation) and T2 (24–30 weeks), and 8 completed data collection at T3 (31 or more weeks). Adherence met expectations for coaching (63%), exercise with a workout partner (100%), and use of the activity tracker (92%). Acceptability was high (100%). ConclusionWe found that recruitment, retention, and adherence are feasible for the FitMoms2B physical activity promotion program. The program and study measures were acceptable to participants in our sample. We provide preliminary support for a randomized controlled trial to study physical activity promotion with virtual coaching, workout partner support, and activity tracking among Black pregnant women with high-risk pregnancies without contraindications to physical activity.

Abstract 778: Atorvastatin modulates serum biomarkers in women at increased risk for breast cancer

Abstract Background Tamoxifen and Aromatase inhibitors have been shown to be highly effective at reducing the incidence of ER-positive breast cancers in women at increased risk, but there are no approved agents for the risk reduction of ER-negative cancers. Evidence from observational and preclinical studies supports the study of statins for breast cancer risk reduction. Objective This study aimed to investigate the effects of Atorvastatin treatment on serum and tissue biomarkers in women at increased risk for breast cancer. Methods Women at increased risk for breast cancer were accrued prospectively at UTMDACC, Breast Medical Oncology High-Risk Clinic. The study was approved by the IRB and all participants signed informed consent. High risk was defined as having a previous history of DCIS, LCIS, or atypical hyperplasia, 5-year projected Gail risk &amp;gt;1.67 %, or lifetime risk &amp;gt;20 % calculated by clinical models. Patients were randomized to no treatment (n=15) or daily 10mg (n=15), 20mg (n=14), or 40mg (n=16) Atorvastatin for 3 months. Fasting blood and breast tissue samples via fine needle aspiration (FNA) were collected at baseline and at study completion. Serum biomarkers were analyzed with ELISA (R&amp;D Systems). The IGF1/IGFBP3 molar ratio was calculated using [IGF1 (ng/mL) x 0.13]/[IGFBP-3 (ng/mL) x 0.035]. The Wilcoxon matched-pairs signed rank test was used to determine significance. Results Tissue biomarker evaluation was previously reported. Serum biomarker levels of IGF1 and its main binding proteins IGFBP1 and IGFBP3 were compared in baseline and post-intervention samples by ELISA analysis. The average change in serum IGF1 (ng/mL) levels between pre- and post-treatment samples (represented as average difference with interquartile range) was +3.5 (-16.8 to 8.7) p=0.98, -0.6 (-23.6 to 15.4) p=0.64, -1.76 (-27.7 to 28.6) p=0.81, and +2.6 (-14.5 to 32.2) p=0.67 in the 0, 10, 20, and 40mg groups respectively. The average change in serum IGFBP1 (pg/mL) was -23.2 (-2372 to 4487) p=0.33, -480 (-4567 to 3008) p=0.72, 429 (-1259 to 3039) p=0.54, and -250 (-3581 to 2492) p=0.94 in the 0, 10, 20, and 40mg groups. The average change in serum IGFBP3 (ng/mL) was -24 (-193 to 98) p=0.72, -119 (-353 to 111) p=0.17, -190 (-433 to 14) p=0.07, and -234 (-369 to -79) p=0.002 in the 0, 10, 20, and 40mg groups. Serum IGF1/IGFBP3 molar ratio was +0.012 (-0.018 to 0.026) p=,0.76, +0.0065 (-0.013, to 0.047) p=0.53, +.0073 (-0.036 to 0.045) p=0.86, and +.027 (-.011 to .062) p=0.058 in the 0, 10, 20, and 40mg groups. Conclusions Serum IGFBP3, which has been associated with breast cancer risk, was decreased in a dose-dependent manner in patients treated with Atorvastatin. The IGF1/IGFBP3 molar ratio was increased in the 40mg group, although not statistically significant (p=.0577). This shows that treatment with Atorvastatin induced changes in circulating biomarkers and that Atorvastatin could be further studied in larger prospective breast cancer prevention trials. Citation Format: Amanda L. Lanier, Johannes Fahrmann, Fatma N. Mustafayev, Angelica Gutierrez Barrera, Powel H. Brown, Banu Arun. Atorvastatin modulates serum biomarkers in women at increased risk for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 778.