Faculty Bibliography

Glomerular injury secondary to infection is a well-documented phenomenon. While the incidence of classic acute post-streptococcal glomerulonephritis (APIGN) has declined in developed countries over the past few decades, IgA-dominant infection-associated glomerulonephritis (IgA PIGN) is emerging as a distinct renal pathology. Characterized by predominant deposition of IgA antibodies within the glomeruli following infection, IgA-dominant PIGN differs from classic PIGN, which typically involves IgG and C3 deposits. This condition is often associated with staphylococcal infections and carries a poor prognosis. It commonly affects older adults and presents with reduced glomerular filtration rate and heavy proteinuria. Due to its rarity and overlapping clinical features with other glomerular diseases, IgA PIGN can be challenging to diagnose, often progressing to end-stage renal disease (ESRD) in approximately 80 % of cases. Prompt diagnosis and management, often requiring renal biopsy, are crucial for improving outcomes. Here, we present a case of IgA-dominant postinfectious glomerulonephritis.

UNLABELLED:Pelvic fractures result in prolonged pain and immobility. In a randomized controlled trial of patients with pelvic fracture, whether abaloparatide (ABL) vs. placebo (PBO) improves healing at 3 months was evaluated. There was no significant difference in CT radiologic healing, physical performance, or change in pain in ABL vs. placebo. PURPOSE/OBJECTIVE:To determine if abaloparatide (ABL) vs. placebo (PBO) improves radiologic healing, pain, and functional outcome at 3 months in patients with pelvic fracture. METHODS:Postmenopausal women and men ≥ 50 years old, enrolled within 4 weeks of pelvic fracture (n = 48), were randomized to blinded ABL vs. PBO. The primary endpoint, fracture healing at 3 months, was assessed by two radiologists using a 5-point scale for cortical bridging from CT images comparing groups by Jonckheere-Terpstra test. The odds of healing (3 or 4 cortices bridged) were analyzed with Mantel-Haenszel relative risks (RR). Pain was assessed monthly by Numeric Rating Scale (NRS). The Short Physical Performance Battery (SPPB; walk speed, chair stands, and balance) evaluated functional mobility. RESULTS:Groups were balanced with a mean age = 82, 93% were female, 98% had multiple rami fractures, 67% had sacral fracture, and 36% had ≥ 1 displaced fracture. CT images at 3 months showed no significant difference in bridging score distribution (indicator of healing) in patients with ABL vs. PBO (p = 0.15) after adjusting for age, sacral fracture, displacement, or compliance. When evaluating individual fractures (n = 81), similar bridging scores were seen with ABL and PBO (p = 0.13). When patients were stratified as healed or not healed, 39% were healed with ABL and 64% healed with PBO (RR 0.61; 95% CI 0.33, 1.12). When looking at the 81 individual fractures, 47% were healed with ABL and 53% healed with PBO (RR = 0.88; 95% CI 0.55, 1.40). Using least square means controlling for age, sacral, and displaced fracture, NRS pain score was higher in the placebo than the ABL group at baseline (p < 0.05), but there were no further group differences in change in pain score SPPB and TUG scores improved over time in both groups without group differences. CONCLUSION/CONCLUSIONS:In this small study, there was no significant difference in CT radiologic healing, physical performance, or change in pain with ABL vs. placebo in patients with acute pelvic fracture. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT04249232 registered January 27, 2020.

Microglia perform the function of CNS macrophages and act as the primary immune cells in the brain. They surveil the environment, phagocytose cellular debris, maintain homeostasis and respond to tissue damage. While under physiological conditions they play a role in supporting neurons, activated microglia participate directly in the degeneration of neurons in the substantia nigra, as the hallmark of the Parkinsons disease (PD). Their detrimental effects result from direct phagocytosis of dopaminergic neurons as well as via neuroinflammation and release of toxic reactive oxygen and nitrogen species. This pathological shift is driven by a complex interplay of genetic predispositions, such as LRRK2 and GBA mutations, and environmental triggers like toxins and gut dysbiosis.A central mechanism of this neurodegeneration involves extracellular α-synuclein acting as a danger signal (DAMP), which activates microglial Toll-like receptors (e.g., TLR2) to initiate a severe inflammatory cascade. Furthermore, the extreme biophysical stability of aggregated α-synuclein overwhelms the microglial endolysosomal network, leading to lysosomal failure, "frustrated phagocytosis," and the active propagation of the disease via exosomal shedding. Relieving this maladaptive chronic neuroinflammation is a primary therapeutic goal. Modern strategies aim to break this vicious cycle through precise interventions like NLRP3 inflammasome inhibition and autophagy enhancement. Concurrently, advanced fluid biomarkers, such as seed amplification assays (SAA), alongside multidimensional neuroimaging techniques (PET, SPECT, MRI), are proving crucial for detecting these early microglial and pathological changes to guide personalized, disease-modifying therapies of PD.

OBJECTIVE:Cesarean delivery (CD) remains a key obstetric quality metric, particularly among nulliparous, term, singleton, vertex (NTSV) pregnancies. In 2024, NTSV CD rate at NYU-LI was 32.9%, exceeding The Joint Commission (TJC) benchmark of ≤30% and demonstrating racial and ethnic disparities. This study aimed to reduce the institutional NTSV CD rate to ≤30% through a multidisciplinary QI initiative while prospectively monitoring safety outcomes and racial disparities. STUDY DESIGN/METHODS:A single-site QI initiative was implemented from 2024-2025 incorporating provider education, patient-centered interventions (TeamBirth and structured labor huddles), standardized labor management, and performance monitoring through monthly case review, clinician feedback, and quarterly equity-focused data review. Outcome measures included monthly overall and quarterly race- and ethnicity-stratified NTSV CD rates. Process measures assessed adherence to evidence-based labor dystocia criteria. Balancing measures included postpartum hemorrhage (PPH) and TJC PC-06 rates. Temporal trends were evaluated using multivariable Poisson regression with adjustment for maternal age, gestational age at delivery, and body mass index. RESULTS:The overall NTSV CD rate decreased from 32.9% in 2024 to 27.8% in 2025, remaining below TJC benchmark in 10 of 12 months. Across the 8-quarter study period, there was a significant decline in the outcome over time (aRR per quarter 0.97, 95% CI 0.95-0.99, p=0.003). Reductions were observed across racial and ethnic groups, including among Black non-Hispanic patients (44.0% to 40.0%) and Asian non-Hispanic patients (37.0% to 29.6%). Adherence to evidence-based labor dystocia criteria remained high, while PPH and PC-06 rates remained stable. CONCLUSIONS:A standardized, multidisciplinary QI initiative was associated with NTSV cesarean delivery rate below the Joint Commission benchmark without increases in maternal or neonatal adverse outcomes. The initiative was also associated with partial reduction in racial disparities in cesarean delivery rates, although persistent inequities remained. Future PDSA cycles will focus on sustaining standardized care and advancing equitable obstetric outcomes.

BACKGROUND:While payers and health systems are increasingly interested in addressing health-related social needs (HRSNs) to reduce health care use and align with value-based care incentives and regulatory requirements, limited evidence enables actionable strategies to manage and address social needs across population groups. OBJECTIVES/OBJECTIVE:To understand the relationship between HRSNs and health care access and use for adults with Medicare, Medicaid, and private health insurance coverage. RESEARCH DESIGN/METHODS:Survey data from adult participants from the All of Us Research Program (2017-2023; n=126,490) and logistic regression were used to examine the association between food insecurity and housing instability and having a usual source of care, seeing a health care provider, and forgoing care due to cost-stratified by payer type. RESULTS:The prevalence of HRSNs varied substantially by insurance: food insecurity affected 49.20% of Medicaid beneficiaries 18-64 years of age, 11.89% of privately insured adults 18-64 years of age, and 5.20% of Medicare beneficiaries 65 years of age and older; housing instability affected 54.61%, 25.18%, and 14.99%, respectively. Food insecurity was associated with lower odds of having a usual source of care for Medicaid and privately insured adults, lower odds of use for privately insured adults, and higher odds of forgone care for all 3 payer types. Housing instability was associated with lower odds of having a usual source of care for all 3 papers and with higher odds of forgone care for all groups. CONCLUSIONS:HRSNs like food insecurity and housing instability vary substantially by payer type and influence health care access and utilization in different ways. This can inform the design of payer-specific health management strategies that incorporate HRSNs.

BackgroundCervical cancer is a preventable disease, and reaching populations who are under-screened and/or at highest risk is essential to the goal of disease elimination. Hispanic women in the US have a disproportionately higher incidence rate than non-Hispanic women.ObjectivePost hoc analysis of the SELF-CERV study of the unique experience and preferences among Hispanic compared to non-Hispanic participants with the goal of facilitating and improving screening and follow-up in more vulnerable populations.MethodsWomen 25 to 65 years who were enrolled performed self-collection (SC) of vaginal samples for high-risk human papillomavirus (hrHPV) testing using a unique device in a simulated at-home environment. For method comparison, a clinician-collected (CC) sample was obtained. Participants also completed usability and screening preference surveys.ResultsA total of 609 participants were consented and 603 used the SC device. Of the 603 SC users, 115 (19.1%) identified themselves as Hispanic/Latinx. Compared to non-Hispanic women, Hispanic women, had significantly lower annual income (p < .001), a lower percentage of private insurance with more uninsured (p < .001) and lower levels of education (p < .001). There was no significant difference between Hispanic and non-Hispanic women in understanding the purpose of cervical cancer screening. No difference was noted in delaying screening, although English Not Primary speaking Hispanic women were somewhat more likely to delay (p = 0.22). Financial barriers were observed to be more of an impediment to Hispanic women compared to non-Hispanic women (p = 0.016). Negative experiences with in-clinic speculum exams were similar; however, Hispanic women (78%) expressed a significantly higher endorsement of SC than non-Hispanic women (62%), (p = 0.001). Both populations reported that they would be more likely to stay up to date with cervical cancer screening with the at-home SC device, but non-Hispanic women to a significantly lesser degree (p = 0.002). In terms of assessing utility of telemedicine in screening, both populations reported similar engagement in healthcare activities, willingness to try new technology and current use of smartphones. Hispanic and non-Hispanic women were both nearly equally divided as to their preference for in-clinic visits vs telehealth.ConclusionsFacilitating screening uptake is especially critical for Hispanic women, who bear a disproportionate burden of cervical cancer diagnoses and mortality while facing more obstacles to screening than non-Hispanic women. A clinically validated and accessible at-home SC alternative holds potential for meaningful impact and improved health outcomes within this community.

BACKGROUND/UNASSIGNED:Healthcare is a major contributor to greenhouse gases. One of the most widely used healthcare services in the USA is colorectal cancer (CRC) screening, indicated for 134 million adults. Recommended screening includes annual faecal immunochemical tests (FITs), CT colonographies every 5 years or colonoscopies every 10 years. OBJECTIVE/UNASSIGNED:To compare the environmental impacts of these tests for CRC screening. DESIGN/UNASSIGNED:We conducted a comparative life cycle assessment of three CRC screening strategies at UCSF. We performed on-site audits to document the resources used for each screening test. We estimated the environmental impacts of these procedures, measured by global warming potential (GWP) and damage to human health. We computed 10-year impacts of each screening strategy using a Markov model. We accounted for uncertainty using hierarchical Monte Carlo simulations. RESULTS/UNASSIGNED:FITs had the lowest environmental impacts, roughly 20 percentage points superior to colonoscopies, and this was robust on sensitivity analyses. Across tests, the biggest cause of environmental harm was car-based transportation of patients and staff. Prioritising FITs over colonoscopies in the USA could enhance population health by 5.2 million disability-adjusted life-years per decade. Transitioning to electric vehicles could reduce the GWP of all screening tests by 15%-20%. CONCLUSIONS/UNASSIGNED:Given the similar efficacy and safety of these tests, payors should probably prioritise FITs for low-risk patients. Governments should decarbonise transportation and mandate environmental product declarations. We call for a closer look at resource-intensive preventative health strategies, which could result in more harm than good if applied to a low-risk population.

APG157DS is a multi-component investigational drug which is currently the subject of multiple cancer trials. It has shown promising efficacy in patients with head and neck cancer. We report its immuno-modulatory effect in a syngeneic mouse model of glioblastoma (GBM). Long-term treatment with APG157DS led to durable tumor remission in 50% of mice, while all vehicle-treated mice reached humane endpoints within 42 days. Mechanistically, the drug induced selective repolarization of tumor-associated macrophages (TAMs) from an immunosuppressive Arg1^high/iNOS^low phenotype to a tumoricidal Arg1^low/iNOS^high state, accompanied by increased intratumoral recruitment of activated (NKp46+) natural killer cells and CD8+ cytotoxic T-cells. APG157DS also suppressed vascular endothelial growth factor (VEGF) and Hypoxia-inducible factor 1-alpha (HIF-1α) expression in tumors, further impairing tumor growth. Notably, APG157DS did not elicit off-target macrophage activation in peripheral tissues such as the spleen, highlighting its selective immune targeting. These findings provide a mechanistic rationale for further clinical development of APG157DS in GBM and potentially other immune-evasive cancers.