Weng, Jessica

ABSTRACT Problem Patients with threatened preterm labor (PTL) are treated with antibiotics, corticosteroids, and magnesium sulfate to mitigate infection, promote fetal lung maturation, provide fetal neuroprotection and overall minimize the impact of prematurity on the neonate. However, the effect of these drugs on the placental inflammatory profile is unknown even though these are given systemically and reach the placenta. We evaluated their action in an ex vivo model of placental inflammation. Method of Study Placental explants from uncomplicated pregnancies were exposed to lipopolysaccharide (LPS) ± azithromycin, betamethasone, and/or magnesium sulfate. Production (lysate) and secretion (supernatant) of pro‐ and anti‐inflammatory cytokines were assessed by ELISA. Results Both pro‐ and anti‐inflammatory cytokines were increased by LPS versus untreated. Azithromycin, or magnesium sulfate did not alter the inflammatory profile by themselves nor when added at the same time or 24 h after LPS. Betamethasone decreased both pro‐ and anti‐inflammatory cytokines only when administered at the same time as LPS, without any effects if delayed. Conclusions Therapeutic interventions classically used for preterm labor (PTL) do not impact the placental inflammatory profile by themselves or in the context of an ex vivo placental explants model of LPS‐induced inflammation, except for betamethasone when administered concurrently with LPS.

Abstract Background Preterm premature rupture of membranes (PPROM) and preterm labor (PTL) are adverse obstetrical outcomes that are strongly associated with cervical high-risk human papilloma virus (cHPV) infection at the time of pregnancy. Persistent cHPV may lead to oncogenic changes in the cervico-vaginal tract and can cause inflammation in gestational tissues, but it is unknown how persistent cHPV infection may affect obstetrical outcomes. The aim of this study is to evaluate whether persistent cHPV infection is associated with recurrent PPROM or PTL among patients with a prior spontaneous preterm birth due to PPROM/PTL, and to examine clinical and pathologic characteristics of cHPV infection in this population. Methods We conducted a retrospective cohort study of patients delivering at Mayo Clinic Rochester or Mayo Clinic Health System (5/1/2018–12/31/2023). Eligible patients had ≥ 1 spontaneous preterm birth due to PPROM/PTL and positive cHPV testing. Demographics and pregnancy outcomes from index and subsequent pregnancies were abstracted. Persistent cHPV was defined as > 1 pregnancy with positive cHPV testing. Results Of 191 index pregnancies, 90 (47.1%) and 30 (33.3%) had one and two subsequent pregnancies, respectively. Patients were predominantly White (91.3%), non‑Hispanic (94.2%), non-smokers (72.0%), and 34.8% were unvaccinated for HPV. Approximately one‑third (31%) experienced recurrent PPROM/PTL in the second pregnancy, with recurrence in 40.7% of those with persistent cHPV and 27.4% without (p = 0.69). Excisional procedures occurred before 12.0% of index pregnancies and 20–24% of subsequent pregnancies; recurrence of PTL/PPROM remained high regardless of procedure history. HPV strain data were available for 132 index pregnancies, and types 16 and 18 were more likely to persist into a subsequent pregnancy (p = 0.0043). CIN persistence occurred at similar rates in patients with and without persistent cHPV infection. Placental inflammation rates were high in both patients with persistent and non-persistent cHPV. Conclusion Recurrent PPROM/PTL, CIN persistence, and placental inflammation were common; a finding independent of persistent cHPV infection, excisional procedure history, or HPV vaccination status. These findings suggest that factors other than cHPV persistence may play a larger role in recurrent preterm birth. Larger studies with higher cHPV prevalence and subsequent pregnancies are needed to provide clarity.

Abstract M.D.-Ph.D. programs in the United States have traditionally followed a “2- n -2” curricular model, with the graduate phase occurring between the pre-clerkship and clerkship portions of medical training. While well established, this format can limit trainee autonomy in shaping their physician-scientist training trajectories. In response, some programs have introduced a “3- n -1” model, allowing students to complete clerkships before beginning Ph.D. training. Our institution implemented multiple flexible curricula in 2017. Understanding why trainees choose one pathway is important as programs consider implementing more adaptable training structures. To investigate these factors, we surveyed M.D.-Ph.D. students at our institution, which offers multiple flexible curricular alternatives, about contributions to their curricular decisions. Responses supported that trainees weigh considerations across medical education, scientific development, and integrated physician-scientist training domains. Although the traditional pathway was a popular option, most students pursued one of the flexible pathways. Our findings suggest that introducing flexibility in the timing of undergraduate medical education and graduate training can support diverse educational, logistical, and personal priorities while maintaining the rigor of physician-scientist training. Offering multiple pathways empowers trainees to design trajectories that best fit their needs. Continued longitudinal studies are needed to assess the long-term impacts of flexible curricula on physician-scientist career outcomes.

Background Patients with advanced cancer experience a substantial amount of existential and emotional distress. Dignity therapy (DT) is a brief, individualized psychotherapy that aims to relieve existential distress and improve the experiences of individuals impacted by serious illness. Aim To evaluate the feasibility and acceptability of virtual DT (vDT) among patients with advanced cancer. Methods This pilot study recruited adult patients with advanced cancer and an expected prognosis >6 months. The vDT intervention consisted of 2 sessions of guided interviews focused on life review, discussion, and development of a generativity document (GD). Feasibility and acceptability were assessed quantitatively and with semi-structured interviews. Effectiveness measures (distress, dignity impact scale, quality of life [QOL]) were administered pre/post intervention. Results Thirty-one patients referred from a palliative care clinic were eligible. Twenty-one consented and 15 received a final GD. Patients who completed final assessments (N = 9) reported satisfaction with their experience and would recommend the therapy to others. Patients found the virtual component of the intervention acceptable, and the majority noted an improvement in their dignity. Qualitative analysis revealed themes of study team effectiveness, perspectives on intervention processes, benefits to self, and benefits to loved ones. Conclusion Participation in vDT intervention was feasible and acceptable for patients. Patients appreciated the connection with the interviewer, the process, and the benefit of having a document to share with loved ones. Preliminary effectiveness data suggest vDT improves sense of dignity.

Abstract The Physician-Scientist Trainee Diversity Summit, hosted by the American Physician Scientists Association and the Burroughs Wellcome Fund, was conceived in 2019 with the mission of developing strategic plans to diversify the physician-scientist community using human-centered design thinking. In June 2024, the second iteration of this conference was held in Raleigh, North Carolina, and brought together a network of scientific and medical organizations to discuss issues of justice, equity, diversity, and inclusion facing physician-scientist trainees. This article summarizes the progress made from the first meeting, the proceedings of the 2024 Summit, and a thematic analysis of the recent meeting, offering tangible solutions to the physician-scientist community for supporting diversity and accessibility.

INTRODUCTION: Perinatal mental illness imparts a significant health burden. A multitude of factors are hypothesized to increase the incidence of perinatal mood and anxiety disorders (PMADs) in the fetal surgical population, including uncertain fetal prognosis and the inherent risks of surgery and preterm delivery. We sought to determine the disease course of PMADs in the fetal surgery population. METHODS: A retrospective chart review was conducted of fetal surgery patients from 2017 to 2021 at a tertiary care center. Demographics, surgical, obstetric, and psychiatric diagnoses were recorded. Standard descriptive analyses were performed. RESULTS: One hundred nineteen eligible patients were identified. Fetal surgery was performed at a median gestational age of 23.0 (range 16.0–34.0) weeks. Laser ablation of placental anastomoses (n=51) and in utero myelomeningocele repair (n=22) were the most common procedures. 26.8% (32/119) had preexisting mood disorders, with 59.3% (19/32) and 53.1% (17/32) on a baseline medication for depression or anxiety, respectively, prior to surgery. 26.4% (23/87) of patients without a history of anxiety or depression had a new diagnosis of PMAD. Two patients experienced suicidal ideation. 6.7% (8/119) and 10.1% (12/119) initiated a new psychiatric medication during or post-pregnancy, respectively. 19.8% (21/113) received a therapy referral. Among patients with baseline anxiety or depression, 62.5% (20/32) experienced an exacerbation postpartum with 25.0% (8/32) referred for therapy, and 34.3% (11/32) changing dose or medication for anxiety and 37.5% (12/32) for depression. CONCLUSION: Among patients undergoing fetal surgery, a high incidence of PMAD was identified. Most patients with prepregnancy anxiety or depression experienced an exacerbation postpartum. Further research into effective supportive interventions is warranted.

The dynamic immunological changes occurring throughout pregnancy are well-orchestrated and important for the success of the pregnancy. One of the key immune adaptations is the maternal immune tolerance towards the semi-allogeneic fetus. In this review, we provide a comprehensive overview of what is known about the innate and adaptive immunological changes in pregnancy and the role(s) of specific immune cells during physiological and pathological pregnancy. Alongside this, we provided details of remaining questions and challenges, as well as future perspectives for this growing field of research. Understanding the immunological changes that occur can inform potential strategies on treatments for the optimal health of the neonate and pregnant individual both during and after pregnancy.