Aberrant nuclear ß-catenin distribution does not prognosticate recurrences of endometrioid endometrial cancers - A retrospective single-institutional study.

OBJECTIVE: Aberrant ß-catenin distribution has been theorized as a predictive biomarker for recurrence in early stage, low grade endometrioid endometrial cancer. METHODS: This retrospective single-institution cohort study reviewed 410 patients with endometrial cancer from May 2018 to May 2022. Only endometrioid histology was included. Demographic and clinicopathological data were collected from the medical records. Univariate and multivariate logistic regressions, and sensitivity analyses for early stage, low grade and no specific molecular profile (NSMP) tumors were performed. RESULTS: 297 patients were included for analysis. Most patients were over 60 years old, White, and with a BMI >30 and early stage low grade disease. Aberrant ß-catenin distribution was found in 135 patients (45.5%) and wild type membranous ß-catenin distribution in 162 (54.5%). While TP53 mutation correlated with endometrial cancer recurrence in this cohort (OR = 4.78), aberrant ß-catenin distribution did not correlate in the overall population (OR = 0.75), the early stage low grade cancers (OR = 0.84), or the NSMP group (OR = 1.41) on univariate or multivariate analysis. No correlation between ß-catenin distribution and local (OR = 0.61) or distant recurrences (OR = 0.90) was detected. CONCLUSIONS: Aberrant ß-catenin distribution did not significantly correlate with recurrence in endometrioid endometrial cancer, nor in the early stage, low grade and NSMP sub-cohorts.

Elevated body mass index in modified natural cycle frozen euploid embryo transfers is not associated with live birth rate.

PURPOSE: To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos. METHODS: This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m2) category: normal weight (18.5-24.9), overweight (25-29.9) or obese (≥ 30). Underweight BMI (< 18.5) was excluded from the analysis. The primary outcome was live birth rate (LBR) and secondary outcome was clinical pregnancy rate (CPR), defined as presence of fetal cardiac activity on ultrasound. Absolute standardized differences (ASD) were calculated to compare descriptive variables and p-values and multivariable logistic regressions with generalized estimating equations (GEE) were used to compare pregnancy outcomes. RESULTS: 562 mNC-FET cycles were completed in 425 patients over the study period. Overall, there were 316 transfers performed in normal weight patients, 165 in overweight patients, and 81 in obese weight patients. There was no statistically significant difference in LBR across all BMI categories (55.4% normal weight, 61.2% overweight, and 64.2% obese). There was also no difference for the secondary outcome, CPR, across all categories (58.5%, 65.5%, and 66.7%, respectively). This was confirmed in GEE analysis when adjusting for confounders. CONCLUSION: While increased weight has commonly been implicated in poor pregnancy outcomes, the effect of BMI on the success of mNC-FET remains debated. Across five years of data from a single institution using euploid embryos in mNC-FET cycles, elevated BMI was not associated with reduced LBR or CPR.

Pregnancy and neonatal outcomes of letrozole versus natural cycle frozen embryo transfer of autologous euploid blastocyst.

PURPOSE: To investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET). METHODS: Our retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5 mg of daily letrozole for 5 days starting on cycle day 2 or 3. Outcomes were compared using absolute standardized differences (ASD), in which a larger ASD signifies a larger difference. Multivariable regression models adjusted for confounders: maternal age, BMI, nulliparity, embryo grade, race, infertility diagnosis, and endometrial thickness. RESULTS: The demographic and clinical characteristics were overall similar. A greater proportion of the letrozole cohort was multiparous, transferred high-graded embryos, and had ovulatory dysfunction. The cohorts had similar pregnancy rates (67.1% LTZ vs 62.1% NC; aOR 1.31, P = 0.21) and live birth rates (60.9% LTZ vs 58.6% NC; aOR 1.17, P = 0.46). LTZ-FET neonates on average were born 5.7 days earlier (P < 0.001) and had higher prevalence of prematurity (18.6% vs. 8.0%NC, ASD = 0.32) and low birth weight (10.4% vs. 5.0%, ASD = 0.20). Both cohorts' median gestational ages (38 weeks and 1 day for LTZ; 39 weeks and 0 day for NC) were full term. CONCLUSION: There were similar rates of pregnancy and live birth between LTZ-FET and NC-FET cycles. However, there was a higher prevalence of prematurity and low birth weight among LTZ-FET neonates. Reassuringly, the median gestational age in both cohorts was full term, and while the difference in gestational length of almost 6 days does not appear to be clinically significant, this warrants larger studies.

Reactivated disseminated tuberculosis in pregnancy: Case report and review of the literature.

This case report describes the evaluation and management of a 32-year-old woman who presented shortly after a fetal demise at 23 weeks of gestation with multiple symptoms, including bloody vaginal discharge. Although the initial diagnostic concern was for metastatic malignancy, the patient was ultimately determined to have disseminated tuberculosis. Genital tuberculosis is common worldwide, yet guidelines for evaluation are limited. This report highlights the relationship between pregnancy-reactivated tuberculosis, and guides clinicians on diagnostic and management considerations in the peripartum period.

Impact of a Potential 20-Week Abortion Ban on Likelihood of Completing Required Views in Second-Trimester Fetal Anatomy Ultrasound.

OBJECTIVE: The aim of this study was to quantify the likelihood of assessing all mandated fetal views during the second-trimester anatomy ultrasound prior to the proposed federal 20-week abortion ban. STUDY DESIGN: Retrospective cohort study of a random sample of 1,983 patients undergoing anatomy ultrasound in 2017 at a tertiary referral center. The difference in proportion of incomplete anatomic surveys prior compared with after 20-week gestation was analyzed using X 2 and adjusted logistic regression; difference in mean days elapsed from anomaly diagnosis to termination tested using t-tests and survival analysis. RESULTS: Incomplete views were more likely with initial ultrasound before 20 weeks (adjusted relative risk: 1.70; 95% confidence interval: 1.50-1.94); 43.5% versus 26.1% were incomplete before and after 20 weeks, respectively. Fetal structural anomalies were identified in 6.4% (n = 127/1,983) scans, with 38.0% (n = 49) identified at follow-up after initial scan was incomplete. 22.8% (n = 29) with an anomaly terminated. CONCLUSIONS: A complete assessment of fetal views during an anatomy ultrasound prior to 20-week gestation is often not technically feasible. Legislation limiting abortion to this gestational age would greatly impact patient's ability to make informed choices about their pregnancies. KEY POINTS: · It is often not technically possible to complete anatomy ultrasound prior to 20-week gestation.. · Often, anomalies are missed during early, incomplete anatomy ultrasounds.. · After the diagnosis of a structural anomaly, one in five chose to terminate the pregnancy..

Residency interviews in the digital era.

In the midst of the SARS-CoV-2 pandemic, the US Association of American Medical Colleges (AAMC) required residency programme transition from in-person to virtual interviews for all applicants. The new virtual format upended a system that has relied on programmes and applicants balancing the likelihood of acceptance with the financial and time demands of cross-country travel.In this commentary, we address the history of residency interviewing in the USA and the emerging changes that are taking place in light of virtual interviews. We discuss the advantages of the new online format, including the reduced cost for applicants and programmes, as well as the decreased carbon footprint.We also discuss the inequities of virtual interviewing, involving a national maldistribution of interviews to only the top-tier candidates. We share previously unpublished data on the number of virtual interviews accepted by Stanford's 2020 residency applicants, compared with those conducted in person in 2019. We find Stanford applicants in all fields accepted more interviews: from a mean of 8 in 2019 to 14 in 2020, a change of 160% on average. Despite this, only half of Stanford 2020 applicants interviewing in the virtual format thought they had accepted more interviews than they would have in person.We comment on how transitions to online interviewing may be affecting medical schools and applicants disproportionately. Ultimately, we highlight the need and offer ideas for additional regulation on behalf of the AAMC to ensure a more equitable distribution of interview opportunities.

Postpartum permanent contraception: updates on policy and access.

PURPOSE OF REVIEW: To describe barriers to provision of postpartum permanent contraception at patient, hospital, and insurance levels. RECENT FINDINGS: Permanent contraception remains the most commonly used form of contraception in the United States with the majority of procedures performed during birth-hospitalization. Many people live in regions with a high Catholic hospital market share where individual contraceptive plans may be refused based on religious doctrine. Obesity should not preclude an individual from receiving a postpartum tubal ligation as recent studies find that operative time is clinically similar with no increased risk of complications in obese compared with nonobese people. The largest barrier to provision of permanent contraception remains the federally mandated consent for sterilization for those with Medicaid insurance. State variation in enforcement of the Medicaid policy additionally contributes to unequal access and physician reimbursement. Although significant barriers exist in policy that will take time to improve, hospital-based interventions, such as listing postpartum tubal ligation as an 'urgent' procedure or scheduling interval laparoscopic salpingectomy prior to birth-hospitalization discharge can make a significant impact in actualization of desired permanent contraception for patients. SUMMARY: Unfulfilled requests for permanent contraception result in higher rates of unintended pregnancies, loss of self-efficacy, and higher costs. Hospital and federal policy should protect vulnerable populations while not preventing provision of desired contraception.

Misoprostol-augmented induction of labour for third trimester fetal demise in a patient with prior hysterotomies.

A 31-year-old G3P2002 with history of two prior caesarean sections presented with influenza-like illness, requiring intubation secondary to acute respiratory distress syndrome. Investigations revealed intrauterine fetal demise at 30-week gestation.She soon deteriorated with sepsis and multiple organs impacted. Risks of the gravid uterus impairing cardiopulmonary function appeared greater than risks of delivery, including that of uterine rupture. Vaginal birth after caesarean was achieved with misoprostol and critical care status rapidly improved.Current guidelines for management of fetal demise in patients with prior hysterotomies are mixed: although the American College of Obstetricians and Gynecologists recommends standard obstetric protocols rather than misoprostol administration for labour augmentation, there is limited published data citing severe maternal morbidity associated with misoprostol use. This case report argues misoprostol-augmented induction of labour can be a reasonable option in a medically complex patient with fetal demise and prior hysterotomies.

Withholding antibiotics does not reduce clinical pregnancy outcomes of natural cycle frozen embryo transfers.

OBJECTIVE: To assess the impact of withholding doxycycline on the success rate of natural cycle frozen embryo transfers (NC-FET). DESIGN: Retrospective cohort study. SETTING: Single academic institution. PATIENT(S): Women undergoing 250 NC-FET with euploid blastocysts performed by a single provider. INTERVENTION(S): One hundred and twenty-five NC-FET cycles performed after January 2019 without antibiotic administration compared with 125 NC-FET cycles before January 2019 with doxycycline administration. MAIN OUTCOME MEASURE(S): Primary outcome: live birth (LB) or ongoing pregnancy rate (OPR, defined as pregnancies ≥13 weeks); secondary outcomes included positive ß-human chorionic gonadotropin (ß-hCG) level and clinical pregnancy rate (CPR, defined as the presence of fetal cardiac activity on ultrasound). RESULT(S): Each group of women comprised 125 NC-FET during the study period of March 2017 to March 2020. The women's mean age was 36.3 years and mean body mass index was 24 kg/m2. Between the two groups, the baseline characteristics were similar, including age, body mass index, race, smoking status, parity, endometrial thickness, Society of Assisted Reproductive Technology diagnosis, and number of prior failed transfers. Comparing NC-FET with doxycycline administration versus without, we found no statistically significant difference in LB-OPR (64% vs. 62.6%), positive ß-hCG (72.8% vs. 74.0%), or CPR (68% vs. 65.9%). After controlling for all variables in a logistic regression, doxycycline still had no effect on LB-OPR. CONCLUSION(S): In this analysis of similar patients undergoing NC-FET by a single provider, withholding doxycycline does not reduce success rates. Given the risks of antibiotics, our findings support withholding their use in NC-FET.

Socioeconomic differences persist in use of permanent vs long-acting reversible contraception: An analysis of the National Survey of Family Growth, 2006 to 2010 vs 2015 to 2017.

OBJECTIVE: Permanent contraception has historically been more prevalent among non-White women with lower education and income. Given increasing popularity of long-acting reversible contraception (LARC), we examine changing sociodemographic patterns of permanent contraception and LARC. STUDY DESIGN: We performed a descriptive analysis of the National Survey of Family Growth (NSFG) from 2006 to 2017, with multivariable analyses of the 2006 to 2010 and 2015 to 2017 cohorts. Using multinomial logistic regression, we investigate predictors of contraceptive category (permanent contraception vs LARC, lower-efficacy contraception vs LARC) in reproductive-aged women. RESULTS: Total 8161 respondents were included in 2 distinct but analogous regression analyses: (1) the most recent survey cohort, 2015 to 2017 and (2) the cohort a decade prior, 2006 to 2010. Over this period, the prevalence of LARC increased nearly 3-fold (6.2%-16.7%), while permanent contraception use trended downwards (22%-18.6%). Yet, in adjusted models, we observed little change in the sociodemographic predictors of permanent contraception: from the early to recent cohort, use of permanent contraception (vs LARC) remained less likely among college graduates (multinomial odds ratio (OR) 0.45 [95% confidence interval 0.21, 0.97]) and Hispanic women (OR 0.41 [0.21, 0.82]). In addition, high income (>$74,999) and metropolitan residence came to predict less use (OR 0.33 [0.13, 0.84] and 0.47 [0.23, 0.97]). Multiparity, advanced age (over ≥35), and marital status remained strong predictors of permanent contraception. CONCLUSION: Although use of LARC nearly equals that of permanent contraception in the most recent NSFG survey, socioeconomic differences persist. Continued effort is needed to detect and address structural barriers to accessing the most effective forms of contraception for women. IMPLICATIONS: Comparing 2006-2010 to 2015-2017, reliance on female permanent contraception decreased while LARC use increased, making prevalence more similar. However, significant socioeconomic differences persist in who chooses permanent contraception, with urban, educated, higher income women more likely to use LARC. Ongoing efforts are needed to understand and reduce economic barriers to LARC.

Anthropology in public health emergencies: what is anthropology good for?

Recent outbreaks of Ebola virus disease (2013-2016) and Zika virus (2015-2016) bring renewed recognition of the need to understand social pathways of disease transmission and barriers to care. Social scientists, anthropologists in particular, have been recognised as important players in disease outbreak response because of their ability to assess social, economic and political factors in local contexts. However, in emergency public health response, as with any interdisciplinary setting, different professions may disagree over methods, ethics and the nature of evidence itself. A disease outbreak is no place to begin to negotiate disciplinary differences. Given increasing demand for anthropologists to work alongside epidemiologists, clinicians and public health professionals in health crises, this paper gives a basic introduction to anthropological methods and seeks to bridge the gap in disciplinary expectations within emergencies. It asks: 'What can anthropologists do in a public health crisis and how do they do it?' It argues for an interdisciplinary conception of emergency and the recognition that social, psychological and institutional factors influence all aspects of care.

Immune therapy and ß-cell death in type 1 diabetes.

Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing ß-cells. The killing of ß-cells is not currently measurable; ß-cell functional studies routinely used are affected by environmental factors such as glucose and cannot distinguish death from dysfunction. Moreover, it is not known whether immune therapies affect killing. We developed an assay to identify ß-cell death by measuring relative levels of unmethylated INS DNA in serum and used it to measure ß-cell death in a clinical trial of teplizumab. We studied 43 patients with recent-onset T1D, 13 nondiabetic subjects, and 37 patients with T1D treated with FcR nonbinding anti-CD3 monoclonal antibody (teplizumab) or placebo. Patients with recent-onset T1D had higher rates of ß-cell death versus nondiabetic control subjects, but patients with long-standing T1D had lower levels. When patients with recent-onset T1D were treated with teplizumab, ß-cell function was preserved (P < 0.05) and the rates of ß-cell were reduced significantly (P < 0.05). We conclude that there are higher rates of ß-cell death in patients with recent-onset T1D compared with nondiabetic subjects. Improvement in C-peptide responses with immune intervention is associated with decreased ß-cell death.