Faculty Bibliography

OBJECTIVE/UNASSIGNED:Timely use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) is vital for managing type 2 diabetes (T2DM) and preventing cardiovascular and renal complications. However, socioeconomic barriers and prescribing inertia may disproportionately affect disadvantaged populations. We examined racial and ethnic differences in the initiation of SGLT2i among Medicaid patients with T2DM. METHODS/UNASSIGNED:Adult participants 18-64 with T2DM and prescribed with metformin were drawn from MarketScan Multistate Medicaid Database (2015-2022) for this retrospective cohort study. We used a Cox proportional hazards model, adjusted for age, sex, type of Medicaid coverage, and comorbidities, to assess time to SGLT2i initiation. RESULTS/UNASSIGNED:Among 13 744 Medicaid patients, non-Hispanic Black patients had an 18% lower rate of SGLT2i initiation compared with non-Hispanic White patients (hazard ratio [HR] = 0.82; 95%CI: 0.75-0.90). This disparity was most pronounced among patients without pre-existing atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease (HR = 0.79; 95%CI: 0.71-0.87). No significant racial/ethnic differences were observed among patients with these conditions. CONCLUSIONS/UNASSIGNED:Significant delays in SGLT2i initiation among Black Medicaid patients-particularly in early stage of diabetes-may increase their risk for long-term complications. Addressing structural barriers through targeted interventions is essential to promote equity in diabetes care.

IMPORTANCE/UNASSIGNED:Ischemic heart disease (IHD), the leading cause of death in the US, is predominantly due to modifiable risk factors. Estimates of IHD mortality attributable to risk factors provide evidence for health policy decision-making. OBJECTIVE/UNASSIGNED:To estimate the burden of IHD death attributable to risk factors in the US from 1990-2023. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Global Burden of Disease Study 2023 (GBD 2023) used vital records and a broad set of epidemiologic data to estimate IHD death rates, risk factor exposure, and relative risk curves for risk-outcome pairs for 1990-2023 for the general population. Data analysis was performed from October 2024 to December 2025. EXPOSURE/UNASSIGNED:Twelve metabolic, behavioral, and environmental risk factors. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcomes were IHD death rates per 100 000 persons, counts, and attributable risks from 1990-2023 by age, sex, and US state. Estimates include 95% uncertainty intervals (UI). IHD death rates were estimated using ensemble modeling methods. Risk exposures were estimated using bayesian meta-regression methods. Relative risks were estimated following the Burden of Proof framework. RESULTS/UNASSIGNED:In 2023, there were 473 000 IHD deaths (95% UI, 414 000-510 000) in the US, a decrease of 58.7% (95% UI, 56.8%-61.0%) in age-standardized rate since 1990. Between 2010 and 2023, there was a 19.0% decrease (95% UI, 15.0%-22.9%) for males and a 24.5% decrease (95% UI, 20.3%-29.7%) for females in IHD death rates. High systolic blood pressure (SBP), dietary risks, and high low-density lipoprotein cholesterol (LDL-C) were the leading risk factors for IHD deaths in 2023, accounting for 47.2% (95% UI, 36.4%-57.0%), 38.6% (95% UI, 17.2%-56.8%), and 28.5% (95% UI, 19.3%-39.6%) of IHD deaths, respectively. Increased exposure to several risk factors substantially increased their attributable burden for IHD deaths in 2023, with high fasting plasma glucose (FPG) increasing 38.8% (95% UI, 11.5%-81.1%) and high body mass index (BMI) increasing 54.5% (95% UI, 41.8%-66.3%) since 1990. Smoking and particulate matter pollution had the greatest decrease in attributable IHD mortality since 1990, at 33.3% (95% UI, 23.6%-41.7%) and 74.9% (95% UI, 46.7%-88.8%), respectively. CONCLUSION AND RELEVANCE/UNASSIGNED:Per the results of this systematic analysis of GBD 2023, a total of 88.7% (95% UI, 83.4%-92.5%) of IHD deaths were attributable to modifiable risk factors in the US in 2023, with high SBP, dietary risks, and high LDL-C being the greatest contributors. High BMI and high FPG showed the largest attribution increases, while exposure to other risks did not increase significantly for the population.

PURPOSE/OBJECTIVE:To develop expert-consensus recommendations for patient selection, technique and clinical management in genicular artery embolization (GAE) using a Delphi process. MATERIALS AND METHODS/METHODS:A working group developed a 75-statement questionnaire. A panel of musculoskeletal and interventional radiologists (IRs), selected based on clinical experience, scientific expertise and geographic diversity, scored each response using a 10-point Likert-scale across three rounds. Consensus was predefined as ≥ 75% of ratings ≥ 7/10. RESULTS:Twenty-nine IRs completed all three rounds. Consensus inclusion criteria for GAE include knee pain refractory to conservative treatment for ≥ 3 months due to osteoarthritis, tendinopathies or prior knee surgery and recurrent hemarthrosis (median 9[IQR 7-10]; 86% ≥ 7). Pre-procedural assessment should include standardized outcome measures, clinical examination and knee radiographs. Contrast-enhanced MRI is optional for osteoarthritis phenotyping and grading of synovitis, differential diagnosis and outcome prediction (8[7-10]; 79% ≥ 7). Via an ipsilateral antegrade transfemoral access, all visible genicular arteries should be catheterized and embolized upon detection of a hypervascular blush (9[7-10]; 76% ≥ 7). No evidence of superiority of either temporary or permanent embolic agents in terms of safety or efficacy has been demonstrated (10[8-10]; 86% ≥ 7). Structured long-term follow-up is recommended, with clinical success defined as achievement of the minimal clinically important difference or individual patient satisfaction (9[7-10]; 83% ≥ 7). Contralateral or repeat GAE may be considered for bilateral knee pain, insufficient response or pain recurrence (8[7-10]; 76% ≥ 7). CONCLUSION/CONCLUSIONS:This Delphi study establishes expert-derived consensus recommendations for GAE, emphasizing broad indications, patient-tailored technique and an active role of the IR in multidisciplinary longitudinal care.

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.

IMPORTANCE/UNASSIGNED:Many patients are diagnosed with atypical lesions or lobular carcinoma in situ (LCIS); however, evidence- and consensus-based guidelines for the management of many of these lesions are limited. OBSERVATIONS/UNASSIGNED:The American Society of Breast Surgeons, in collaboration with the Society of Breast Imaging and College of American Pathology, assembled a steering group to create guidelines for the management of atypical lesions and LCIS, inclusive of flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), classic LCIS (C-LCIS), and the variant LCIS forms pleomorphic LCIS (P-LCIS) and florid LCIS (F-LCIS). The natural history of ADH, ALH, and C-LCIS suggests that these lesions are associated with an elevated future breast cancer risk; therefore, patients diagnosed with these lesions should be recommended to undergo comprehensive risk assessment and counseling about breast cancer risk-reducing strategies. The magnitude of future breast cancer risk associated with P-LCIS and F-LCIS remains uncertain, yet if these lesions are determined to be hormone receptor positive, risk-reducing medications should be considered. There is no evidence that FEA is associated with an elevated future breast cancer risk. A second pathology review confirmation is recommended for ADH, should be considered for FEA, and is not necessary for ALH or LCIS. Currently available evidence supports the need to diagnostically excise most ADH, P-LCIS, and F-LCIS cases identified on core biopsy, although some ADH cases fulfilling strict criteria and multidisciplinary consensus can be observed. P-LCIS and F-LCIS require a negative margin, but ADH does not. ALH and C-LCIS can be safely observed if the core biopsy diagnosis is concordant with imaging features (ie, radiographic-pathologic concordance is established). Provided radiologic-pathologic concordance is confirmed, diagnostic excision is generally not indicated after a diagnosis of FEA alone. CONCLUSIONS AND RELEVANCE/UNASSIGNED:These guidelines provide evidence-informed, consensus-based recommendations for the management of atypical lesions of the breast, including ADH, ALH, FEA, C-LCIS, P-LCIS, and F-LCIS. Practicing clinicians who treat patients with atypical breast lesions or LCIS should consider integrating these guidelines into clinical management.

BACKGROUND/UNASSIGNED:It is unknown how the increased range of motion and improved gait mechanics provided by total ankle arthroplasty (TAA) affects the progression of subtalar arthritis compared with ankle arthrodesis (AA). We hypothesized that patients treated with TAA would have a lower incidence of postoperative subtalar arthrodesis (SA) compared to AA. METHODS/UNASSIGNED: <.05. RESULTS/UNASSIGNED: > .05). In a multivariate analysis, AA remained associated with increased risk of requiring SA (OR = 1.90, CI = 1.01-3.56). CONCLUSION/UNASSIGNED:In this study, we found a significantly higher incidence of subtalar arthrodesis following AA compared with TAA. Surgeons may consider the risk of progression to SA when deciding between TAA and AA for patients with advanced ankle arthritis, particularly in preoperative counseling for patients without existing subtalar arthritis, as TAA may offer an opportunity to mitigate this risk. LEVEL OF EVIDENCE/UNASSIGNED:Level III, retrospective comparative study.

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.

CONTEXT/BACKGROUND:Osteopathic manipulative treatment (OMT) utilizes manual techniques to address somatic dysfunctions (SDs) and promote physiologic function. Although SDs commonly develop following traumatic injury, the role of OMT in postinjury remains incompletely characterized. Patients recovering from trauma frequently experience persistent pain and functional limitations requiring ongoing healthcare utilization. To address this need, we established a novel OMT for trauma program (OTP) to complement interventions for patients with subacute and chronic postinjury pain and mobility impairments. OBJECTIVES/OBJECTIVE:This study aims to evaluate the growth and effectiveness of the novel OTP over its first 3 years. METHODS:We retrospectively analyzed data for all patients treated at the OTP between January 1, 2021 and December 31, 2023. The outcomes included patient volume, relative value units (RVUs), and referral patterns as well as changes in pain, mobility, and other subjective improvement patients attributed to OMT. We performed subgroup analyses of patients who reported a mechanism of injury (MOI, "Injured") and those who did not ("No MOI"). Data are presented as percentages or medians (interquartile range [IQR]). RESULTS:During its first 3 years, the OTP provided 279 OMT sessions for 95 patients (41 [43.16 %] male and 54 [56.84 %] female; median 52 [41.50-64.50] years-old), applying a trauma-informed biomechanical OMT model. Quarterly patient encounters, RVUs generated, and new patient referrals increased per calendar-year quarter (CYQ; r=0.74, 0.62 and 0.56 with p=0.0028, 0.028, and 0.016, respectively). Referral patterns shifted from trauma/acute care surgery (T/ACS) and Physical Medicine and Rehabilitation (PM&R; 51.85 to 25.0 % and 33.33 to 2.78 %) toward OTP patient referrals and Primary Care referrals (0-19.44 % and 11.11-47.22 %). Median pain scores decreased immediately following the first OMT session (3 [2-5] on a 10-point pain scale). OTP patients whose first follow-up was within the study period (61, 64.21 %) reported a similar decrease between OMT sessions #1 and #2 (4 [3-6]). All patients reported improved mobility immediately after OMT. Additional benefits that patients attributed to the OTP included improvements in daily activity level (75.41 %), mood (60.66 %), sleep quality (36.07 %), and pain-free periods (36.07 %). The rate of immediate post-OMT complications (universally described as musculoskeletal discomfort or pain) was 2.87 %. We detected no significant differences during subgroup analyses. Median pain scores improved similarly between Injured and No MOI subgroups immediately after OMT session #1 (3 [2-5] vs. 3.5 [1.5-4.25], p=0.337) and between OMT sessions #1 and 2 (4 [3-6] vs. 4 [1.5-6], p=0.363). CONCLUSIONS:Our data demonstrate that not only is it possible to integrate a novel OTP into a level 1 trauma center but also that such a program is likely to grow significantly over time and consistently provide potentially beneficial OMT services for patients who do and do not identify a MOI. Programs like the OTP may provide a distinct modality to help improve postinjury pain and mobility limitations, among other potential benefits, although further analysis is necessary to assess causality. The present data informed updates to OTP operations, including the implementation of prospective, higher-fidelity data collection to enable more detailed and accurate analyses. Further research, including comparative studies, is warranted to explore the potential benefits of OMT for the trauma population.