University of California, San Francisco

The maternal-fetal interface has long been considered as a frontier for an evolutionary arms race due to the close juxtaposition of genetically distinct tissues. In hemochorial species with deep placental invasion, including in humans, maternal stroma prepares its defenses against deep trophoblast invasion by decidualization, a differentiation process characterized by increased stromal cell matrix production, and contractile force generation. Decidualization has evolved from an ancestral wound healing response of fibroblast activation by the endometrial stroma. On the placental side, a new trophoblast cell type in great apes has recently evolved, called extravillous trophoblast (EVT), with an exceptionally high invasive capability. Using HTR8, and differentiated EVTs from trophectodermal stem cells, we show that EVTs partly counter decidual myofibroblast activation derived defenses. This reversal in decidual defenses is achieved by secreted antagonists of Transforming Growth Factor β/Bone morphogenic pathway, specifically Emilin-1 and Gremlin-1. Emilin-1 and Gremlin-1 reverse TGFβ activation in decidual cells, reducing high collagen production, and expression of genes associated with myofibroblast transformation. We also show that these secreted TGFβ antagonists can functionally reverse acquired decidual resistance to trophoblast invasion. As our work highlights new mechanisms evolved by trophoblasts to regulate stromal invasibility, it has broader implications in other invasive processes, including wound healing, and cancer metastasis.

Background Hepatocellular carcinoma (HCC) has become a leading indication for liver transplant (LT), with HCC registrants increasing more than six-fold in the past two decades, accompanied by a significant rise in older candidates. Given this trend and the influence of hepatitis C (HCV) treatments, updated data on aging and changing etiologies in older HCC patients are needed. This study examines age trends, clinical characteristics, and transplant outcomes by comparing older (70+), younger HCC patients, and non-HCC patients. Methods All adult LT candidates (18+) in the UNOS/OPTN registry (2012-2022) were analyzed, categorized by HCC status and age (<70 or 70+). Regression coefficients compared HCC and non-HCC registrants and recipients by age group. Results The aging trend among LT registrants was more pronounced in HCC patients. From 2012 to 2022, the mean age of HCC registrants rose from 58.7 to 62.9, with those aged 70+ increasing from 4.2% to 15.0%. Non-HCC registrants saw minimal change, with a stable mean age of 53 years and a modest rise in those 70+ from 2.1% to 4.7%. HCV prevalence among HCC patients decreased from 37.5% to 27.4%, while non-HCC patients dropped from 14.8% to 5%. Post-transplant outcomes for older HCC recipients remained favorable, with 1-year and 5-year survival rates of 91% and 71%, respectively, comparable to older non-HCC patients (87% and 69%). Conclusion Among over 132,000 liver transplant registrants from 2012 to 2022, the age of HCC candidates increased, with a growing proportion aged 70 and older, while the age and proportion of older adults among non-HCC registrants remained stable. This demographic shift underscores the importance of enhanced frailty assessments to improve outcomes for older HCC patients.

Introduction Latinx individuals are disproportionately affected by alcohol use disorder (AUD). Understanding Latinx individuals’ barriers and facilitators to reach AUD-related goals can help implement culturally and linguistically concordant interventions to improve alcohol-related outcomes. Methods We conducted semi-structured qualitative interviews with Latinx, Spanish-speaking men with AUD within 20 weeks of hospital discharge who were seen by an addiction consult team during hospitalization in an urban, safety-net hospital in San Francisco. Interviews focused on the facilitators and barriers to participants’ AUD-related goals pre-, during, and post-hospitalization. We recorded and transcribed interviews and used a mixed deductive and inductive analytic approach until we reached thematic saturation (n = 10). Results We identified three major themes: 1. Hospitalization was an actionable moment for change; 2. Social factors were closely intertwined with AUD goals; and 3. Accessible addiction, physical health, and mental health services can help achieve AUD goals. Conclusions Hospitalization may serve as a facilitator for Latinx individuals with AUD to achieve AUD goals. Addressing social determinants of health including housing, immigration status, and social support networks before, during, and after hospitalization, may help facilitate AUD goals. Providing language-concordant and accessible services may decrease barriers to achieving AUD goals.

Introduction Pancreatoduodenectomy (PD) may occasionally be indicated for complete removal of periampullary (duodenal and ampullary) adenomas (PAs). As compared with malignant indications, PD for benign or pre-malignant disease is often associated with increased morbidity. While the Spigelman classification assesses malignancy risk for familial adenomatous polyposis (FAP)-related duodenal adenomas, no malignancy risk score (MRS) exists for non-FAP related PAs. We developed a MRS for non-FAP related PAs undergoing PD to weigh risk of malignancy and postoperative morbidity. Methods We retrospectively analyzed patients with non-FAP related PA who underwent PD at eight institutions (2010-2022). Patient and lesion factors associated with final malignant pathology were identified using multivariable logistic regression to create MRS. Postoperative complications were assessed according to MRS. Results Of 127 patients, 59 (46.5%) had evidence of malignancy on final pathology. The odds of malignancy were higher in patients with older age ≥65 years (OR3.2, p=0.01), bile duct ≥9mm (OR3.3, p=0.009), preoperative symptoms (OR7.7, p=0.002), and high-grade dysplasia (HGD, OR7.5, p<0.001). A MRS was derived ranging from 0 to 6: age≥65=1, bile duct≥9mm=1, symptomatic=2, HGD=2. Patients were stratified into low (MRS1–2, n=26), intermediate (MRS3–4, n=59), and high-risk groups (MRS5–6, n=26), with malignancy rates increasing with MRS (10.3%, 44.1%, and 88.2%, p<0.001). Patients in the no/low-risk group (MRS0-2) had higher odds of major postoperative complications compared with patients in the intermediate/high-risk group (MRS≥3, OR2.9, p=0.047). Conclusion This novel MRS stratifies the risk of malignancy in non-FAP related PAs managed with PD. This score can be used to counsel patients who may require PD for complete tumor removal about their risk of harboring malignancy and their risk of major postoperative complications.

A woman in her 70s with well-controlled HIV on antiretroviral therapy presented with a several-month history of an asymptomatic perianal lesion. Skin examination showed a 0.5–1 cm red-pink, shiny, exophytic papule with visible telangiectasias near the anal verge. The differential diagnosis was most concerning for Kaposi sarcoma. A shave biopsy with electrodessication was performed for both diagnostic and therapeutic purposes. Histology revealed a dome-shaped lesion with a diffuse inflammatory infiltrate composed of lymphocytes and eosinophils. The vessels in the superficial and mid-dermis showed cuboidal-to-columnar endothelial cells with nuclear enlargement, conspicuous nucleoli, and ample cytoplasm. These findings were consistent with angiolymphoid hyperplasia with eosinophilia (ALHE). Only 2.4% of ALHE occur on the genitals and fewer than 1% on the buttocks. Additionally, few of these are reported in female patients and none in female patients with HIV. At 12 months post-treatment, the patient remains without evidence of recurrence.

Background Storage of packed red blood cells (RBCs) for transfusion leads to biochemical and morphological changes, increasing hemolysis risk. Urate levels in blood bags at donation contribute to the molecular heterogeneity and hemolytic propensity of stored RBCs. However, studies to date have been underpowered to investigate at scale the contribution of donor demographics and genetics to the heterogeneity in urate levels across donations. Study Design and Methods Urate levels were measured in 13,091 RBC units from the REDS study. Characteristics tested included hemolysis parameters (spontaneous, osmotic, oxidative) at storage end and post‐transfusion hemoglobin (Hb) increments in recipients. Donor demographics, urate levels, and genetic variants were analyzed for associations with these outcomes. Results Elevated urate levels were linked to male sex, older age, high BMI, and Asian descent. Units with high urate levels exhibited increased spontaneous and osmotic hemolysis, while oxidative hemolysis was unaffected. Genetic variants in SLC2A9 (V282I) and ABCG2 (Q141K) were strongly associated with elevated urate, particularly in Asian donors. Post‐transfusion analyses revealed that units from female donors carrying these variants were associated with reduced Hb increments, with up to a 31% reduction in efficacy. This effect was not observed in male donors. Discussion RBC urate levels and genetic traits significantly impact storage quality and transfusion outcomes. These findings highlight the importance of donor molecular characteristics for optimizing transfusion strategies. Moreover, genetic and metabolic insights may inform donor recruitment efforts, providing health feedback to volunteers while ensuring effective transfusion products.

As access to doula services expands through state Medicaid coverage and specific initiatives aimed at improving maternal health equity, there is a need to build and improve upon relationships between the doula community, hospital leaders, and clinical staff. Previous research and reports suggest rapport‐building, provider education, and forming partnerships between community‐based organizations and hospitals can improve such relationships. However, few interventions or programs incorporating such approaches are described in the literature. This article describes the development and 5 core components of the Champion Dyad Initiative (CDI), a novel program that uses bidirectional feedback between SisterWeb, a community‐based doula organization, and 5 clinical sites (4 hospitals and one birthing center) to ensure pregnant and birthing people receive fair and equitable treatment. We also describe implementation challenges related to documentation, funding, and institutional support. The CDI is a promising model for community‐based doula organizations and health care institutions to develop collaborative partnerships, build respectful doula‐provider relationships, and work toward improving the pregnancy‐related care that Black, Indigenous, and people of color receive in hospital and birth center settings. It is our hope that this innovative initiative can serve as a model that can be adapted for other locales, organizations, and hospitals.

Purpose of Review Addressing diabetes distress (DD), the emotional demands of living with diabetes, is a crucial component of diabetes care. Most individuals with type 2 diabetes and approximately half of adults with type 1 diabetes receive their care in the primary care setting. This review will provide guidance on addressing DD and implementing targeted techniques that can be tailored to primary care patients. Recent Findings Structured educational, behavioral, and emotion-focused techniques have promise for treating DD. These interventions are unlikely to require advanced training and can be feasibly integrated into primary care settings without creating additional burdens on time or resources. Summary Interventional studies examining treatment for DD are limited, leaving a gap for clear direction and consensus on how to target and treat DD in primary care patients. This review consolidates recommendations and approaches from recent findings on how to treat DD within the context of primary care.

Background and Aims Military veterans demonstrate high rates of heavy drinking and insomnia, but few if any studies have tested real‐world, daily associations between sleep and alcohol use within this population. Moreover, although daily diary and experimental studies among civilians have found negative associations between alcohol use and sleep, these patterns change with consecutive days of drinking and may differ for those with insomnia. This study measured (a) acute and cumulative day‐level associations between sleep and alcohol use among heavy‐drinking US veterans and (b) the extent to which insomnia moderates these associations. Design Self‐reported ambulatory assessments occurring daily for 14 days. Setting USA. Participants Heavy‐drinking veterans ( n = 118, 84% male, 79% White, M = 39y) with sleep complaints. Seventy‐one met criteria for insomnia disorder. Measurements Participants completed a semi‐structured clinical interview and baseline self‐report measures, followed by 14 consecutive days of morning sleep diaries. Data were analyzed using multilevel models. Findings Insomnia moderated day‐level associations between alcohol use and sleep. Heavier drinking was associated with worse same‐night sleep quality among those without insomnia [ b = −0.06; 95% confidence interval (CI) = −0.09, −0.03], but this pattern was not statistically significant among those with insomnia ( b = 0.02; 95% CI = −0.01, 0.04). Similarly, more consecutive nights of poor sleep efficiency were linked to lower drinking quantity among those without insomnia [incidence rate ratio ( IRR ) = 0.91; 95% CI = 0.83, 1.00), while better sleep efficiency was linked to heavier next‐day drinking among those with insomnia ( IRR = 1.01; 95% CI = 1.00, 1.01). More consecutive nights of drinking were linked to shorter sleep duration, regardless of insomnia status ( b = −0.09; 95% CI = −0.18, −0.002). Conclusions US military veterans with insomnia do not appear to experience the same negative day‐level associations between alcohol use and sleep that those without insomnia report. However, over time, drinking is linked to worse sleep in both groups.

We present the case of a fully vaccinated 39-year-old male with no pertinent past medical history who initially presented with De Quervain’s tenosynovitis which was successfully treated with a corticosteroid injection. His symptoms recurred during a COVID-19 infection, which was treated with a repeat corticosteroid injection. Symptoms recurred during an influenza infection and were subsequently treated with a first dorsal compartment release. The etiology of De Quervain’s tenosynovitis remains unclear. It has classically been categorized as a noninflammatory degenerative process, but recent evidence suggests a possible inflammatory connection. Here, we present a case of recurrent De Quervain’s tenosynovitis exacerbated by two distinct viral infections. We hypothesize that viral-induced systemic inflammation led to localized recurrence of inflammation within the tendon sheath. Further studies including cytokine analysis and inflammatory markers are needed to advance this hypothesis.

Objective. To study the effect of dose-rate in the time evolution of chemical yields produced in pure water versus a cellular-like environment for FLASH radiotherapy research. Approach. A version of TOPAS-nBio with Tau–Leaping algorithm was used to simulate the homogenous chemistry stage of water radiolysis using three chemical models: (1) liquid water model that considered scavenging of eaq⁻, H• by dissolved oxygen; (2) Michaels & Hunt model that considered scavenging of •OH, eaq‒, and H• by biomolecules existing in cellular environment; (3) Wardman model that considered model 2) and the non-enzymatic antioxidant glutathione (GSH). H2O2 concentrations at conventional and FLASH dose-rates were compared with published measurements. Model 3) was used to estimate DNA single-strand break (SSB) yields and compared with published data. SSBs were estimated from simulated yields of DNA hydrogen abstraction and attenuation factors to account for the scavenging capacity of the medium. The simulation setup consisted of monoenergetic protons (100 MeV) delivered in pulses at conventional (0.2857 Gy s⁻¹) and FLASH (500 Gy s⁻¹) dose rates. Dose varied from 5–20 Gy, and oxygen concentration from 10 µM–1 mM. Main Results. At the steady state, for model (1), H2O2 concentration differed by 81.5%± 4.0% between FLASH and conventional dose-rates. For models (2) and (3) the differences were within 8.0%± 4.8%, and calculated SSB yields agreed with published data within 3.8%± 1.2%. A maximum oxygen concentration difference of 60% and 50% for models (2) and (3) between conventional and FLASH dose-rates was found between 2 × 10⁶ and 9 × 10¹³ ps for 20 Gy of absorbed dose. Significance. The findings highlight the importance of developing more advanced cellular models to account for both the chemical and biological factors that comprise the FLASH effect. It was found that differences between pure water and cellular environment models were significant and extrapolating results between the two should be avoided. Observed differences call for further experimental investigation.

Introduction Studies examining preoperative weight loss using pharmacotherapy in metabolic and bariatric patients are limited. The objective was to investigate if patients taking a low‐dose formulation of phentermine had improved weight loss. Methods This study was a randomized, placebo‐controlled trial including patients undergoing laparoscopic Roux‐en‐Y gastric bypass and sleeve gastrectomy. Anthropometric and serological data were collected during the initial consult visit and again during two follow‐up visits. Lomaira is a low‐dose formulation of phentermine. Patients took 8‐mg tablets three times a day for 14 weeks. The primary outcome of this study was weight loss, which was measured as percentage total weight loss (%TWL) and change in body mass index (BMI). Results Among 53 participants randomized, 45 (85%) completed the trial. Participants were predominantly female (91%); the mean age was 41 years (SD = 11); and the mean initial BMI was 48.4 kg/m² (SD = 8.2 kg/m²). Average weight loss was 6.2 kg (SD = 6) in the treatment group versus 1.1 kg (SD = 4.54) in the placebo group (p = 0.001). Average % TWL was greater in treatment Group 4.7 ± 4.3 versus placebo Group 1.1 ± 3.6, p = 0.001. Multivariate regression analysis demonstrated that preoperative medication use was significantly associated with greater %TWL (p = 0.004). There was no difference in OR time or post‐operative complications between the groups. Conclusions Low‐dose phentermine is efficacious and safe for preoperative weight loss in patients undergoing metabolic and bariatric surgery.

Background Understanding the risks and effects of gestational weight gain (GWG) is a prominent area of perinatal research but approaches for quantifying GWG are evolving and remain underdeveloped, especially in clinical settings for underserved demographic subgroups. To fill this gap, we demonstrated and compared six GWG metrics across pre-pregnancy BMI classifications: total GWG, trimester-specific linear rate of GWG, adherence to total and trimester-specific recommendations, area under the curve, and GWG for gestational age z-scores. Methods We used clinical data on 44,801 pregnant people from community-based health care organizations with extensive longitudinal measures and substantial representation of understudied subgroups. Results Total GWG was lower in individuals with higher pre-pregnancy BMI; yet more temporally resolved analyses revealed differences in trimester-specific weight change. Differences included common first trimester weight loss in people with pre-pregnancy class II or III obesity and substantial first trimester weight gain in people with pre-pregnancy underweight, with the greatest pre-pregnancy BMI-related variation in GWG occurring in the second trimester. These differences are reflected to varying degrees in the AUC and GWG z-score metrics. Conclusions Our findings inform development of GWG guidelines within BMI categories, especially in obesity subclasses and underweight, and selection, refinement, and application of GWG metrics in future research. GWG metrics differ to varying degrees across BMI categories in a population consisting of several underserved subgroups: pregnant people of color, with larger body sizes, or with lower incomes. Stronger evidence on safe levels of first trimester weight loss and obesity class-specific recommendations is needed.

Background Mobile Health Clinics (MHCs) are an alternate form of healthcare delivery that may ameliorate current rural–urban health disparities in chronic diseases and have downstream impacts on the health system by reducing costs. Evaluations of providers’ time allocation on MHCs are scarce, hindering knowledge transfer related to MHC implementation strategies. Methods Retrospective economic cost was assessed using business ledgers and expert assessments in 2023 US Dollar (USD) from 2022 to 2023. Time motion observational study assessed nurse practitioner (NP) and community health worker (CHW) time allocation and compared them between patients residing in isolated rural areas (hereafter isolated rural patients) and patients experiencing houselessness (PEH) sub-populations. Procedure codes were assessed retrospectively for each patient encounter (n = 1,981) over one year (April 2022 to April 2023). We used statistical significance tests (chi-square and Fisher’s Exact) to evaluate difference across sub-populations. Results Intervention start-up and operational costs totaled 275,000USD and 308,000USD, respectively, with the largest allocations to the modified recreational vehicle (RV) unit and labor. NP attributed 32% of time on direct care (mean = 153.00 min (SD = 37.80 min)), 38% on indirect care (186.0 (53.40)), and 21% on MHC tasks (104.00 (23.94)). CHW spent 47% of time on MHC tasks (182.00 (29.46)), 22% on medical care tasks (85.01 (SD 81.97)), and 22% on social needs tasks (87.70 (86.71 min)). NP time allocation did not differ significantly between isolated rural patients and PEH (p > 0.01), but CHW time did (p < 0.01). Of all procedures, 31.3% were vaccinations (N = 438), 27.0% were Covid-19 related (N = 377), 12.8% were outside referrals (N = 179), and 11.8% were point of care testing. Healthcare utilization varied between patient sub-populations, with Isolated Rural patient use dominated by Covid-19 and Influenza vaccines whereas PEH use was dominated by point of care testing (p < 0.01). Conclusion Patient sub-populations require varying provider time in different tasks and variable economic resources for interventions. As local policy makers balance resources and community health needs, a complete understanding of the resources required to operate an MHC and use of provider time is essential for informed decision making and successful implementation in underserved communities.

Background Patients admitted with acute decompensated heart failure (ADHF) are vulnerable to declines in kidney function, but the exact mechanisms are unknown. Two novel hemodynamic markers, pulmonary artery pulsatility index (PAPI) and aortic pulsatility index (API) represent composite right and left-ventricular function respectively. Methods Consecutive unique patient admissions for ADHF to a single quaternary medical center with placement of a pulmonary artery (PA) catheter between 2015-2021 were reviewed. Cubic and linear regression models were used to examine the association between these markers with baseline estimated glomerular filtration rate (eGFR) and in-hospital eGFR slope. Multivariable Cox proportional hazards models were used to examine the association between PAPI and API with the need for dialysis via linkage of a national database. Covariates included demographics, comorbid conditions, home medications and baseline eGFR. Results The cohort included N = 753 patients with mean (SD) age 62.2 (14.4), eGFR 58.0 (27.1) ml/min/1.73m ² . For every halving of PAPI, there was a 3.3 (95% CI 1.5, 5.1) ml/min/1.73 m ² lower baseline eGFR, and a 0.78 (95% CI 0.32, 1.25) ml/min/1.73 m ² /week lower in-hospital eGFR slope. Over a median follow-up time of 30.3 months, lower PAPI was associated with higher hazard of dialysis during the follow-up period (HR 1.44 (95%CI 1.06, 1.96) per halving). There was no association between API with baseline eGFR, in-hospital eGFR slope, or dialysis. Conclusions Lower PAPI was associated with a lower baseline eGFR, lower in-hospital eGFR slope and higher risk of dialysis. API was not associated with any kidney outcomes.

Objectives The purpose of this investigation was to evaluate the utility of the Centers for Disease Control (CDC) Surgical Wound Classification (SWC) in predicting surgical site infection (SSI) after orthopaedic trauma procedures. Design Retrospective cohort study. Setting Level I academic trauma center. Patients/Participants Adult patients with operatively treated fractures of the leg, ankle, and hindfoot between 2007 and 2022. Intervention N/A. Main Outcome Measurements Presence of SSI was determined by selective chart review of patients who met the screening variables for repeated procedures, open fracture, abscess or wound debridement, intraoperative cultures, or infectious disease consultation (n = 551). Results Two thousand seven hundred ninety-one fractures among 2780 patients (n = 11 with bilateral fractures) were included. The overall infection rate was 2.3% (n = 63), and SWC was significantly associated with infection rates (I/clean: 1.0%, II/clean-contaminated: 3.4%, III/contaminated: 6.2%, IV/dirty: 9.8%, P < 0.001). When compared with Class I, Classes II through IV had increased odds of infection (odds ratio [OR] II: 3.5, P = 0.012; OR III: 6.8, P < 0.001; OR IV: 11.0, P < 0.001). Subgroup analysis of Classes II and III demonstrated no difference in odds of infection. When stratifying open versus closed fractures, there was no statistical association between CDC SWC and odds of infection. Conclusions The CDC SWC has notable limitations for patients with orthopaedic trauma, with ambiguity of classification assignment and decreased discriminatory ability within the central classes. While overall SWC is associated with infection, the relationship seems to be confounded by the effect of open versus closed fractures. Alternative classification systems may have improved utility for stratifying risk in orthopaedic patients. Level of Evidence III.

Background The impact of certain comorbidities on mechanical thrombectomy (MT) outcomes remains largely unexplored. Diabetes mellitus (DM) and admission hyperglycemia have been associated with poor clinical outcomes for patients treated with MT. In this study, we sought to investigate the effects of DM and admission hyperglycemia on MT outcomes. Methods Following PRISMA guidelines, a systematic literature search was conducted in Medline, Embase, Scopus, and Web of Science databases. Data regarding successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2b), functional independence (modified Rankin Scale [mRS] 0–2), excellent outcomes (mRS 0–1), symptomatic intracranial hemorrhage (sICH), and mortality were extracted from the included studies. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using random effects model. Results Twenty-one studies comprising 9708 patients were included. A total of 2311 patients (24%) had a history of DM, and 2026 patients (21%) had admission hyperglycemia. Admission hyperglycemia was associated with significantly lower odds of mTICI ≥2b (OR = 0.7, 95% CI = 0.55–0.89), mRS 0–2 (OR = 0.47, 95% CI = 0.41–0.53), and mRS 0–1 (OR = 0.43, 95% CI = 0.34–0.55) as compared to normoglycemic state. Patients with hyperglycemia had significantly higher rates of sICH (OR = 2.05, 95% CI = 1.66–2.54) and mortality (OR = 1.99, 95% CI = 1.58–2.52) than normoglycemic patients. Diabetes mellitus was associated with significantly high rates of mortality (OR = 1.74, 95% CI = 1.31–2.3) and lower rates of mRS 0–2 (OR = 0.60, 95% CI = 0.48–0.76) in sensitivity analyses. Conclusion Our results indicate that admission blood glucose levels and DM can negatively affect MT outcomes. Further research should focus on optimizing MT outcomes for these patients.