Reducing health disparities in endometrial cancer care in 2024.

PURPOSE OF REVIEW: To summarize the most recent publications explaining disparities among patients diagnosed with endometrial cancer and identify areas of improvement. RECENT FINDINGS: Racial disparities in endometrial cancer care have been identified along the cancer continuum including risk, diagnosis, access to treatment, and overall survival. The mortality gap in endometrial cancer is one of the top five widest Black-White mortality gaps among all cancer diagnoses in the United States. Many publications have demonstrated that the disparities exist, the aim of this review is to identify actionable areas of improvement. To mitigate racial disparities, we must acknowledge that Black patients are at higher risk of high-risk subtypes of endometrial cancer, and their presentation can vary from what is considered typical for the most common type of endometrial cancer. We must address that practice recommendations for diagnosis may not be generalizable to all races and ethnicities, and that racism has an impact on how providers approach a work-up for Black vs. White patients. Finally, we must improve access to appropriate treatment by steadfastly adhering to recommended practice guidelines regardless of race/ethnicity and improving efforts to enroll a diverse patient population to clinical trials. SUMMARY: In this review, we sought to identify specific and actionable areas of improvement to reduce racial disparities in endometrial cancer care.

The Family and Pregnancy Pop-Up Village: Developing a one-stop shop of services to reduce pregnancy care-related inequities in San Francisco.

INTRODUCTION: Centering affected individuals and forming equitable institutional-community partnerships are necessary to meaningfully transform care delivery systems. We describe our use of the PRECEDE-PROCEED framework to design, plan, and implement a novel care delivery system to address perinatal inequities in San Francisco. METHODS: Community engagement (PRECEDE phases 1-2) informed the "Pregnancy Village" prototype, which would unite key organizations to deliver valuable services alongside one another, as a recurring "one-stop-shop" community-based event, delivered in an uplifting, celebratory, and healing environment. Semi-structured interviews with key partners identified participation facilitators and barriers (PRECEDE phases 3-4) and findings informed our implementation roadmap. We measured feasibility through the number of events successfully produced and attended, and organizational engagement through meeting attendance and surveys. RESULTS: The goals of Pregnancy Village resonated with key partners. Most organizations identified resource constraints and other participation barriers; all committed to the requested 12-month pilot. During its first year, 10 pilot events were held with consistent organizational participation and high provider engagement. CONCLUSION: Through deep engagement and equitable partnerships between community and institutional stakeholders, novel systems of care delivery can be implemented to better meet comprehensive community needs.

Factors Associated with Inpatient Narcotic Medication Usage after Robotic-assisted Laparoscopy.

STUDY OBJECTIVE: Describe factors that contribute to an increased narcotic medication use after robotic-assisted laparoscopic (RAL) surgery. DESIGN: A retrospective cohort. SETTING: A teaching hospital. PATIENTS: All patients undergoing RAL surgery by gynecologist oncologists at St. Joseph's Hospital and Medical Center over a 3-year period. INTERVENTIONS: RAL by gynecologist oncologists. MEASUREMENTS AND MAIN RESULTS: Using retrospective chart review, patients who underwent RAL surgery from 2012 to 2015 in the division of gynecologic oncology were identified; 757 patients were eligible for inclusion in the study. Total narcotic use during the postoperative hospital stay was converted to oral morphine milligram equivalents (OME). Bivariate correlations of total OME narcotics to multiple variables were evaluated using Spearman's rho. The average age, body mass index, and length of stay were 53.76 years (17-92), 31.75 kg/m2 (17-56), and 1.56 days (range, 0-19), respectively. Increased OME correlated positively with body mass index (Spearman's rho = .077, p = .036), any intraoperative complication (Spearman's rho = .05, p = .886), any postoperative complication (Spearman's rho = .16, p <.0001), length of stay in days (Spearman's rho = .282, p <.0001), procedure time (Spearman's rho .023, p = .52), and total anesthesia time (Spearman's rho, .032). Total OME narcotics were correlated negatively with age of 65 years or older (Spearman's rho, -.144, p <.0001) and use of patient-controlled analgesia (Spearman's rho, -.185, p <.0001). CONCLUSION: Age younger than 65 years seems to be a predictor for increased requirement of total morphine equivalent medication after RAL surgery, whereas patient-controlled analgesia use had a negative association.

Coiled-coil destabilizing residues in the group A Streptococcus M1 protein are required for functional interaction.

The sequences of M proteins, the major surface-associated virulence factors of the widespread bacterial pathogen group A Streptococcus, are antigenically variable but have in common a strong propensity to form coiled coils. Paradoxically, these sequences are also replete with coiled-coil destabilizing residues. These features are evident in the irregular coiled-coil structure and thermal instability of M proteins. We present an explanation for this paradox through studies of the B repeats of the medically important M1 protein. The B repeats are required for interaction of M1 with fibrinogen (Fg) and consequent proinflammatory activation. The B repeats sample multiple conformations, including intrinsically disordered, dissociated, as well as two alternate coiled-coil conformations: a Fg-nonbinding register 1 and a Fg-binding register 2. Stabilization of M1 in the Fg-nonbinding register 1 resulted in attenuation of Fg binding as expected, but counterintuitively, so did stabilization in the Fg-binding register 2. Strikingly, these register-stabilized M1 proteins gained the ability to bind Fg when they were destabilized by a chaotrope. These results indicate that M1 stability is antithetical to Fg interaction and that M1 conformational dynamics, as specified by destabilizing residues, are essential for interaction. A "capture-and-collapse" model of association accounts for these observations, in which M1 captures Fg through a dynamic conformation and then collapses into a register 2-coiled coil as a result of stabilization provided by binding energy. Our results support the general conclusion that destabilizing residues are evolutionarily conserved in M proteins to enable functional interactions necessary for pathogenesis.

Dostarlimab for the Treatment of Endometrial Cancer: A Review.

There have been many recent changes in the treatment of endometrial cancer, most recently with the US Food and Drug Administration's (FDA) approval of dostarlimab in conjunction with standard-of-care chemotherapy in the frontline setting for mismatch repair-deficient (dMMR) populations. This review sought to summarize the publications and studies that have led to this practice-changing approval. Dostarlimab is an immune checkpoint inhibitor with a favourable safety profile and proven efficacy in the treatment of endometrial cancer, particularly dMMR endometrial cancer. FDA-approved treatments for mismatch repair-proficient endometrial cancer remain limited.

Advanced endometrial cancer-The next generation of treatment: A society of gynecologic oncology journal club clinical commentary.

In February of 2024, the Society of Gynecologic Oncology (SGO) hosted a journal club focused on new treatment options for the management of advanced and metastatic endometrial cancer. This clinical commentary is intended to provide a summary report of that presentation. The session described the importance of molecular characterization shown in the work of The Cancer Genome Atlas (TCGA). The updated 2023 FIGO staging of endometrial cancer was reviewed. The panel then described the role of upfront immunotherapy for the treatment of advanced or recurrent endometrial cancer as demonstrated in four recent trials (RUBY, NRG-GY018, AtTEnd, and DUO-E studies). The DUO-E study uniquely examined the combination immunotherapy with a PARP inhibitor. The trials had unique differences in inclusion criteria, primary outcomes, and length of maintenance therapy, but all boasted similarly promising results particularly in mismatch repair deficient (dMMR) endometrial cancer. This era of rapid innovation in advanced and recurrent endometrial cancer will hopefully enhance individualized treatment approaches and improved outcomes for patients with endometrial cancer.

Role of discrimination and resilience on birth weight: A systematic examination in a sample of Black, Latina, and White women.

INTRODUCTION: Health inequities begin before birth with Black women being more likely to have low birth weight babies than White and Latina women. Although both Latina and Black women experience discrimination, only Black women appear to be affected. METHODS: In this study using medical records and face-to-face interviews, we systematically examined the role of discrimination (daily, environmental, vicarious) on continuous birth weight (controlling for gestational age and baby's gender) in a sample of 329 Black, Latina, and White pregnant women, as well as whether familism, prayer, and/or discrimination attribution buffered this association. RESULTS: Linear regression analyses revealed that only prayer acted as a resilience factor, with Latina women appearing to benefit from prayer in the link between vicarious and daily discrimination on birth weight conditional on gestational age, whereas Black women showed no moderation and White women showed an exacerbation in the link. DISCUSSION: The results of this study suggest that sociocultural norms may play a role in explaining the Latina epidemiological paradox, but more research is needed to understand the significance.

Targeted beta therapy of prostate cancer with 177Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1).

PURPOSE: Chimeric antibody Miltuximab®, a human IgG1 engineered from the parent antibody MIL-38, is in clinical development for solid tumour therapy. Miltuximab® targets glypican-1 (GPC-1), a cell surface protein involved in tumour growth, which is overexpressed in solid tumours, including prostate cancer (PCa). This study investigated the potential of 89Zr-labelled Miltuximab® as an imaging agent, and 177Lu-labelled Miltuximab® as a targeted beta therapy, in a mouse xenograft model of human prostate cancer. METHODS: Male BALB/c nude mice were inoculated subcutaneously with GPC-1-positive DU-145 PCa cells. In imaging and biodistribution studies, mice bearing palpable tumours received (a) 2.62 MBq [89Zr]Zr-DFO-Miltuximab® followed by PET-CT imaging, or (b) 6 MBq [177Lu]Lu-DOTA-Miltuximab® by Cerenkov imaging, and ex vivo assessment of biodistribution. In an initial tumour efficacy study, mice bearing DU-145 tumours were administered intravenously with 6 MBq [177Lu]Lu-DOTA-Miltuximab® or control DOTA-Miltuximab® then euthanised after 27 days. In a subsequent survival efficacy study, tumour-bearing mice were given 3 or 10 MBq of [177Lu]Lu-DOTA-Miltuximab®, or control, and followed up to 120 days. RESULTS: Antibody accumulation in DU-145 xenografts was detected by PET-CT imaging using [89Zr]Zr-DFO-Miltuximab® and confirmed by Cerenkov luminescence imaging post injection of [177Lu]Lu-DOTA-Miltuximab®. Antibody accumulation was higher (% IA/g) in tumours than other organs across multiple time points. A single injection with 6 MBq of [177Lu]Lu-DOTA-Miltuximab® significantly inhibited tumour growth as compared with DOTA-Miltuximab® (control). In the survival study, mice treated with 10 MBq [177Lu]Lu-DOTA-Miltuximab® had significantly prolonged survival (mean 85 days) versus control (45 days), an effect associated with increased cancer cell apoptosis. Tissue histopathology assessment showed no abnormalities associated with [177Lu]Lu-DOTA-Miltuximab®, in line with other observations of tolerability, including body weight stability. CONCLUSION: These findings demonstrate the potential utility of Miltuximab® as a PET imaging agent ([89Zr]Zr-DFO-Miltuximab®) and a beta therapy ([177Lu]Lu-DOTA-Miltuximab®) in patients with PCa or other GPC-1 expressing tumours.

Complete Genome Sequence of a Porcine Polyomavirus from Nasal Swabs of Pigs with Respiratory Disease.

Metagenomic sequencing of pooled nasal swabs from pigs with unexplained respiratory disease identified a large number of reads mapping to a previously uncharacterized porcine polyomavirus. Sus scrofa polyomavirus 2 was most closely related to betapolyomaviruses frequently detected in mammalian respiratory samples.

Group A Streptococcal M1 Protein Provides Resistance against the Antimicrobial Activity of Histones.

Histones are essential elements of chromatin structure and gene regulation in eukaryotes. An unexpected attribute of these nuclear proteins is their antimicrobial activity. A framework for histone release and function in host defense in vivo was revealed with the discovery of neutrophil extracellular traps, a specialized cell death process in which DNA-based structures containing histones are extruded to ensnare and kill bacteria. Investigating the susceptibility of various Gram-positive pathogens to histones, we found high-level resistance by one leading human pathogen, group A Streptococcus (GAS). A screen of isogenic mutants revealed that the highly surface-expressed M1 protein, a classical GAS virulence factor, was required for high-level histone resistance. Biochemical and microscopic analyses revealed that the N-terminal domain of M1 protein binds and inactivates histones before they reach their cell wall target of action. This finding illustrates a new pathogenic function for this classic GAS virulence factor, and highlights a potential innate immune evasion strategy that may be employed by other bacterial pathogens.