Faculty Bibliography

Bowel endometriosis is a complex condition predominantly impacting women in their reproductive years, which may lead to chronic pain, gastrointestinal symptoms, and infertility. This review highlights current approaches to the diagnosis and management of bowel endometriosis, emphasizing a multidisciplinary strategy. Diagnostic methods include detailed patient history, physical examination, and imaging techniques like transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI), which aid in preoperative planning. Management options range from hormonal therapies for symptom relief to minimally invasive surgical techniques. Surgical interventions, categorized as shaving excision, disc excision, or segmental resection, depend on factors such as lesion size, location, and depth. Shaving excision is preferred for its minimal invasiveness and lower complication rates, while segmental resection is reserved for severe cases. This review also explores nerve-sparing strategies to reduce surgical morbidity, particularly for deep infiltrative cases close to the rectal bulb, anal verge, and rectosigmoid colon. A structured, evidence-based approach is recommended, prioritizing conservative surgery to avoid complications and preserve fertility as much as possible. Comprehensive management of bowel endometriosis requires expertise from both gynecologic and gastrointestinal specialists, aiming to improve patient outcomes while minimizing long-term morbidity.

While there is agreement on the indications for intracranial pressure monitoring (ICPm) in patients with sTBI, there continues to be controversy concerning the ideal timing of its implementation. It is within this context that we decided to investigate whether a protocolization approach could optimize the timeliness of ICPm implementation. Neurosurgical and SICU providers agreed to a 3-tier protocol to identify patients with sTBI who could benefit from timelier ICPm implementation. The monthly compliance was monitored for a 9-month period. The study included a pre-protocolization group of 11 patients (2022) and a post-protocolization group of 9 patients (2023-2024). There was a trend toward earlier use of ICPm but the difference did not achieve statistical significance; there was no difference in the mortality rates between groups. A protocolization approach to the treatment of patients with sTBI developed with a consensus strategy may lead to earlier implementation of ICPm and possibly improved functional outcome.

Precision medicine approaches to cancer treatment aim to exploit genomic alterations that are specific to individual patients to tailor therapeutic strategies. Yet, some targetable genes and pathways are essential for tumor cell viability even in the absence of direct genomic alterations. In underrepresented populations, the mutational landscape and determinants of response to existing therapies are poorly characterized because of limited inclusion in clinical trials and studies. One way to reveal tumor essential genes is with genetic screens. Most screens are conducted on cell lines that bear little resemblance to patient tumors, after years of culture under nonphysiologic conditions. To address this problem, we aimed to develop a CRISPR screening pipeline in three-dimensionally grown patient-derived tumor organoid (PDTO) models. A breast cancer PDTO biobank that focused on underrepresented populations, including West African patients, was established and used to conduct a negative-selection kinome-focused CRISPR screen to identify kinases essential for organoid growth and potential targets for combination therapy with EGFR or MEK inhibitors. The screen identified several previously unidentified kinase targets, and the combination of FGFR1 and EGFR inhibitors synergized to block organoid proliferation. Together, these data demonstrate the feasibility of CRISPR-based genetic screens in patient-derived tumor models, including PDTOs from underrepresented patients with cancer, and identify targets for cancer therapy. Significance: Generation of a breast cancer patient-derived tumor organoid biobank focused on underrepresented populations enabled kinome-focused CRISPR screening that identified essential kinases and potential targets for combination therapy with EGFR or MEK inhibitors. See related commentary by Trembath and Spanheimer, p. 407.

Cancer of unknown primary (CUP) constitutes between 2% and 5% of human malignancies and is among the most common causes of cancer death in the United States. Brain metastases are often the first clinical presentation of CUP; despite extensive pathological and imaging studies, 20%-45% of CUP are never assigned a primary site. DNA methylation array profiling is a reliable method for tumor classification but tumor-type-specific classifier development requires many reference samples. This is difficult to accomplish for CUP as many cases are never assigned a specific diagnosis. Recent studies identified subsets of methylation quantitative trait loci (mQTLs) unique to specific organs, which could help increase classifier accuracy while requiring fewer samples. We performed a retrospective genome-wide methylation analysis of 759 carcinoma samples from formalin-fixed paraffin-embedded tissue samples using Illumina EPIC array. Utilizing mQTL specific for breast, lung, ovarian/gynecologic, colon, kidney, or testis (BLOCKT) (185k total probes), we developed a deep learning-based methylation classifier that achieved 93.12% average accuracy and 93.04% average F1-score across a 10-fold validation for BLOCKT organs. Our findings indicate that our organ-based DNA methylation classifier can assist pathologists in identifying the site of origin, providing oncologists insight on a diagnosis to administer appropriate therapy, improving patient outcomes.

IMPORTANCE/UNASSIGNED:Chronic pain is common among individuals with dialysis-dependent kidney failure. OBJECTIVE/UNASSIGNED:To evaluate the effectiveness of pain coping skills training (PCST), a cognitive behavioral intervention, on pain interference. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This multicenter randomized clinical trial of PCST vs usual care was conducted across 16 academic centers and 103 outpatient dialysis facilities in the US. Adults undergoing maintenance hemodialysis and experiencing chronic pain were randomly assigned to PCST or usual care in a 1:1 ratio. Participants were followed in the trial for 36 weeks. Enrollment began on January 4, 2021, and follow-up ended on December 21, 2023. INTERVENTIONS/UNASSIGNED:PCST consisting of 12 weekly coach-led sessions via video or telephone conferencing, followed by 12 weeks of daily interactive voice response sessions. Usual care had no trial-driven pain intervention. MAIN OUTCOMES/UNASSIGNED:The primary outcome was pain interference measured with the Brief Pain Inventory (BPI) Interference subscale (score range of 0-10, with higher scores indicating more pain interference). Secondary outcomes included pain intensity, pain catastrophizing, quality of life, depression, and anxiety. RESULTS/UNASSIGNED:A total of 643 participants (mean [SD] age, 60.3 [12.6] years; 288 [44.8%] female) were randomized, with 319 assigned to PCST and 324 assigned to usual care. At week 12 (primary end point), the PCST group had a larger reduction in the BPI Interference score than the usual care group (between-group difference, -0.49; 95% CI, -0.85 to -0.12; P = .009). The effect persisted at week 24 (between-group difference in BPI Interference score, -0.48; 95% CI, -0.86 to -0.11) but was diminished at week 36 (between-group difference in BPI Interference score, -0.34; 95% CI, -0.72 to 0.04). A decrease in BPI Interference score greater than 1 point (minimal clinically important difference) occurred in 143 of 281 participants (50.9%) in the PCST group vs 108 of 295 participants (36.6%) in the usual care group at 12 weeks (odds ratio, 1.79; 95% CI, 1.28-2.49) and 142 of 258 participants (55.0%) in the PCST group vs 113 of 264 participants (42.8%) in the usual care group at 24 weeks (odds ratio, 1.59; 95% CI, 1.13-2.24). Favorable changes with PCST were also apparent for secondary outcomes of pain intensity, quality of life, depression, and anxiety at weeks 12 and/or 24, as well as for pain catastrophizing at weeks 24 and 36. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial of patients undergoing maintenance hemodialysis, PCST had benefits on pain interference and other pain-associated outcomes. While the effect on the overall cohort was of modest magnitude, the intervention resulted in a clinically meaningful improvement in pain interference for a substantial proportion of participants. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04571619.

OBJECTIVES/OBJECTIVE:Women with germline BRCA1/2 pathogenic variants (gBRCA1/2) are recommended to undergo annual breast MRI and mammography. Our objective was to describe the frequency of insurance denials for annual breast MRIs in women with gBRCA1/2 and determine denial trends. METHODS:Women with gBRCA1/2 following in a high-risk breast cancer clinic with breast MRIs ordered from 2020 to 2021 were identified and cross-referenced with a database of insurance denials. Radiology records were queried to determine if screening breast MRIs were performed in 2020 and 2021. Rates of MRI denials and outcomes after appeal were determined. RESULTS:There were 682 women with gBRCA1/2 who had screening breast MRIs ordered from 2020 to 2021, including 318 (47 %) BRCA1, 356 (52 %) BRCA2, and 8 (1 %) with both. 73 women (11 %) had an MRI denied. Women insured through Medicaid had the highest rates of denials (2020: 7 %, 2021: 18 %), followed by commercial insurance (2020: 6 %, 2021: 9 %). There were significantly more denials in 2021 compared to 2020 (p = 0.044), and 2021 denials were more likely to be denied on appeal. Of women with denials, 4 (14 %) in 2020 and 5 (11 %) in 2021 did not have a screening MRI performed. One patient with DCIS had an MRI denial prior to diagnosis. CONCLUSION/CONCLUSIONS:Breast MRI insurance denials were present in 11 % of this high-risk cohort, and 14 % of women with denials did not undergo annual screening. There were significantly more denials in 2021, suggesting worsening barriers for these patients and added burden on providers to appeal for appropriate screening tests.

The recent escalation of racism in the U.S. during the COVID-19 pandemic points to the importance of examining the association between experienced racism and sexual health. Based on data from a nationally representative survey conducted in the U.S. in October 2020 (n = 1,915), Chi-square tests and multivariable logistic regressions were estimated to examine the association between experience of racism and changes in sex life during the pandemic. We further performed a causal mediation analysis using the bootstrap technique to assess the mediating role of psychological distress in the observed association between the experience of racism and changes in sex life. Among the respondents, the proportions reporting better, worse, or no change in sex life were, respectively, 15%, 21%, and 64%. Experiencing racial discrimination during COVID-19 was significantly associated with worsening sex life (adjusted odd ratio [AOR] = 1.53; 95% confidence interval [CI] = 1.04, 2.25). Respondents with experienced racism were also more likely to report psychological distress (AOR = 1.68; 95% CI = 1.09, 2.59). About one-third (32.66%) of the observed association between experienced racism and worsening sex life was mediated through psychological distress. Addressing racism and its association with psychological distress has the potential to improve sexual health and reduce related racial and ethnic disparities.

The organization of a cardio-oncology clinic and overall program is designed to provide comprehensive cardiovascular care to patients who are at risk of or have developed cardiovascular sequelae during or following cancer treatments. In this article, we summarize the core components of a contemporary cardio-oncology program, including its core members (cardiologists, oncologists, clinical pharmacists, advanced practice providers, nurses, and coordinators), key services (risk assessment, treatment planning, cardiac imaging, intervention, and management), and practical integration within the health care system.

BACKGROUND/UNASSIGNED:Caregiving has been associated with high blood pressure in middle-aged and older women, but this relationship is understudied among younger Black women, a population at high risk for hypertension. We examined the associations of caregiving stress and caregiving for high-needs dependents with incident hypertension among reproductive-age women in the JHS (Jackson Heart Study), a cohort of community-dwelling Black adults. METHODS/UNASSIGNED:We included 453 participants, aged 21 to 44 years, with blood pressure <140/90 mm Hg, and not taking antihypertensive medication at baseline (2000-2004). Caregiving stress over the past 12 months was assessed via a single item in the global perceived stress scale. Caregiving for a high-needs dependent status was assessed via a question on hours per week spent caregiving for children (≤5 years or disabled) or older adults. Incident hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or self-report of taking antihypertensive medication at follow-up exams in 2005 to 2008 and 2009 to 2013. RESULTS/UNASSIGNED:Over a median follow-up of 7.4 years, 43.5% of participants developed hypertension. Participants with moderate/high versus no/low caregiving stress had a higher incidence of hypertension (51.7% versus 40.6%). Higher caregiving stress was associated with incident hypertension after adjustment for sociodemographic and clinical factors, health behaviors, and depressive symptoms (hazard ratio, 1.39 [95% CI, 1.01-1.94]). Being a caregiver for a high-needs dependent was not associated with incident hypertension (adjusted hazard ratio, 0.88 [95% CI, 0.64-1.21]). CONCLUSIONS/UNASSIGNED:Higher caregiving stress among reproductive-age Black women was associated with incident hypertension. Hypertension prevention approaches for this high-risk population may include caregiving stress management strategies.

BACKGROUND:Physicians perform many difficult skills, but notifying loved ones about the death of a family member is a particularly challenging skill that requires specific training. Descriptions of such training are lacking in the literature. We developed a formative standardised patient encounter on death notification over the telephone for fourth-year medical students and evaluated their qualitative perspectives, including emotional safety. APPROACH/METHODS:Embedded within a fourth-year advanced communication skills workshop in 2019, a case was introduced to practice telephone death notification. Students had a preparatory didactic lesson, received formative peer feedback, and participated in faculty-led debriefs. EVALUATION/RESULTS:Eighty-eight medical students at one medical school in the United States participated in debriefing sessions after a communication skills workshop during the fourth-year capstone course. The debriefing sessions were audio-recorded and transcribed. Fifty-seven of those students completed postsession surveys. Transcripts and surveys were qualitatively analysed using content analysis to code responses, extract salient categories, and distil into themes. Three general themes emerged: communication challenges, emotional responses, and appreciation for the experience. Communication challenges included using language about death, experiences of silence, complications of distance and driving, and communication by phone. Students described the case as "challenging," "uncomfortable," "intense," and "emotional." Despite these strong feelings, students expressed appreciation for the experience, noting appropriateness of the preparation and debrief, a sense of safety, and realistic encounters. IMPLICATIONS/CONCLUSIONS:Telephone death notification training was a valued, realistic, and emotionally safe experience. Students felt appropriately challenged, but adequately supported. These skills can be included in formative communication skills curricula.