Faculty Bibliography

OBJECTIVE:Although treatment guidelines recommend pulse steroids, induction treatment of lupus nephritis (LN) varies significantly among providers. This paper aims to explore evidence that intravenous pulse provides pharmacological benefits along with improved clinical efficacy without greater toxicity compared with high-dose oral glucocorticoids justifying inclusion for all active LN. METHODS:We conducted a systematic literature review (SLR) using the term 'pulse glucocorticoids in LN' in order to identify studies that summarise the pharmacologic mechanisms of glucocorticoids, reviewed the historical use of glucocorticoids in SLE, and compared pulse therapy with high-dose oral treatment related to their efficacy and toxicities. RESULTS:SLR demonstrated that non-genomic mechanisms of action are more associated with pulse than oral steroids. Some observational studies reported improved renal responses with pulse steroids but in exchange for more adverse metabolic bone disease effects (eg, osteoporosis and avascular necrosis) as well as infections and, importantly, mortality. CONCLUSIONS:Current guidelines promoting pulse therapy for all forms of proliferative LN (and in the case of American College of Rheumatology 2024 treatment guidelines, even isolated class V membranous LN) rely on structured evidence grading processes, including expert consensus and observational data, but are not based on head-to-head randomised controlled trial comparisons. Therefore, there can be an ongoing debate regarding the best approach. The SLR identifies a distinct pharmacological benefit unique to pulse treatment, though without direct evidence necessary for the treatment of LN; includes observational studies with evidence of superior efficacy, but not consistently; and identifies a higher risk of adverse effects. In our opinion, the data advocates for a more selective approach to treatment, foregoing universal treatment with pulse steroids, based on a toxicity versus benefit assessment that patients with mild disease do not require the additional risks.

IMPORTANCE/UNASSIGNED:Lung cancer screening (LCS) with low-dose computed tomography (CT) remains underused in the US, partly because of incomplete smoking history documentation in electronic health records (EHRs) and limited time for shared decision-making in primary care. OBJECTIVE/UNASSIGNED:To determine whether a patient-facing, EHR-integrated tool combined with clinician-facing clinical decision support improves the identification of LCS-eligible patients and the ordering of low-dose CT compared with clinician-facing tools alone. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This pragmatic, unstratified, randomized clinical trial with parallel groups was conducted from March 29, 2024, to March 28, 2025, at primary care clinics at University of Utah Health and New York University Langone Health. Adults aged 50 to 79 years with a documented smoking history, an active patient portal account, and a primary care visit in the preceding year were included. Study 1 enrolled patients with uncertain LCS eligibility (10 to 19 pack-years, unknown pack-years, or missing quit date); study 2 enrolled patients with documented eligibility (20 or more pack-years and currently smoking or quit smoking within 15 years). INTERVENTIONS/UNASSIGNED:The control included the clinician-facing Decision Precision+ tool (preventive care reminders and a shared decision-making tool). The intervention included the Decision Precision+ tool as well as the MyLungHealth tool, which collected detailed smoking history (study 1) and delivered personalized education and risk/benefit information (studies 1 and 2) via the patient portal in English and Spanish. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcomes were the proportion of patients newly identified as eligible for LCS (study 1) and low-dose CT ordering rates (study 2) over 12 months. Analyses used intention-to-treat mixed-effects logistic regression. RESULTS/UNASSIGNED:There were 31 303 randomized participants, including 26 729 in study 1 (13 144 [49.2%] female; 13 580 [50.8%] male; median [IQR] age, 62 [55-69] years) and 4574 in study 2 (2230 [48.8%] female; 2344 [51.2%] male; median [IQR] age, 63 [56-69] years). In study 1, the MyLungHealth tool increased new LCS eligibility identification (635 of 13 412 [4.7%] vs 308 of 13 317 [2.3%]; adjusted odds ratio, 2.19; 95% CI, 1.99-2.42; P < .001). In study 2, low-dose CT ordering was higher in the intervention arm (474 of 2312 [20.5%] vs 434 of 2262 [19.2%]; adjusted odds ratio, 1.16; 95% CI, 1.04-1.30; P = .008). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial, integrating a patient-centered tool into primary care EHR workflows increased the identification of patients eligible for LCS and the ordering of low-dose CTs. The relative increases in these primary outcomes were substantial, but absolute increases were more modest. Research on more intensive interventions is warranted to evaluate their ability to further improve LCS screening. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT06338592.

OBJECTIVES/OBJECTIVE:New York has seen increasing utilization of consumer-directed care, whereby recipients of Medicaid-funded personal care hire, train, and supervise their own caregivers. This study evaluates how switching from agency-based to consumer-directed care impacts health, functional, and social outcomes among care recipients. DESIGN/METHODS:Retrospective cohort study. SETTING AND PARTICIPANTS/METHODS:Enrollees in a large health plan in the New York Metropolitan area who received Medicaid-funded personal care. METHODS:Linked 2017-2022 administrative and clinical assessment data were examined for 10,479 health plan enrollees initially receiving agency-based care, of whom 844 (8%) switched to consumer direction during the observation period. Propensity score matching and doubly robust multivariable regression models were used to examine the impact of switching on 5 outcomes: all-cause hospitalization, falls, any decline in social activities, emergency department visits, and functional decline (impairment in activities of daily living). RESULTS:After matching, groups were well-balanced on baseline covariates. Switching to consumer direction was associated with significantly lower odds of hospitalization (OR, 0.45; P < .001), a lower odds of falls (OR, 0.69; P =.032), and a lower odds of decline in social activities (OR, 0.61; P =.006). Switching was also associated with less functional decline (β, -0.09; P < .001). CONCLUSIONS AND IMPLICATIONS/CONCLUSIONS:For those who chose to do so, switching to consumer-directed care was associated with a range of positive outcomes. Reconfiguring older adults' care convoys to include trusted, consistent caregivers may enhance health monitoring and social well-being. Policies that create administrative barriers to choosing consumer-directed care models should be evaluated for their potential to produce unintended health consequences.

BACKGROUND:Foundation models have shown remarkable potential in medical imaging by leveraging extensive pretraining on general datasets to enable fine-tuning for specific tasks. This is thought to be particularly beneficial for tasks where annotated data is scarce. A key underlying assumption, however, is that these models can learn from small amounts of training data more efficiently than existing state-of-the-art models. PURPOSE/OBJECTIVE:This study aims to characterize the performance of two major foundation segmentation models (SAM and MedSAM) when fine-tuned to segment neuroanatomic structures across a spectrum of dataset sizes, compared to a standard fully-supervised UNet model. METHODS:This study used 1,113 T1-weighted 3D MRIs from the Human Connectome Project's Young Adult cohort with corresponding Freesurfer-generated, manually-refined segmentations of 93 gray and white matter regions. The dataset was divided into 891 (80%) training MRIs, 111 (10%) validation MRIs, and 111 (10%) testing MRIs. SAM and MedSAM models were first fine-tuned and compared against a standard UNet model using Dice score to establish the baseline performance using all training 3D volumes. Subsequently, MedSAM and UNet models were fine-tuned across a varying number of training volumes to assess performance with diminishing dataset size, down to a single MRI, as well as no MRIs (zero-shot) for the MedSAM and SAM models. RESULTS:Using the entire training set, UNet outperformed MedSAM and SAM across most regions, with median Dice scores of 0.88 versus 0.82 and 0.84, respectively (p < 0.001). With diminishing dataset size, UNet continued to perform as well as or better than MedSAM in the three studied regions, down to even a single 3D volume. In the zero-shot setting, SAM and MedSAM showed some ability to segment with overall median Dice scores of 0.66 and 0.59, respectively. CONCLUSIONS:SAM and MedSAM did not outperform a standard UNet model in segmentation tasks, even in extremely limited training data settings, contrary to the foundation model hypothesis, suggesting that foundation models do not necessarily yield superior fine-tuned performance compared to standard segmentation models in the low data setting. Instead, the potential benefit of foundation models will depend on the characteristics of the task at hand and the behavior and capacity of the specific foundation model in question. Thus, it will be essential to benchmark against standard supervised deep learning methods for each distinct application to demonstrate the added value of using a foundation model.

MOTIVATION/UNASSIGNED:A defining characteristic of biological tissue is its cell type composition. Many pathologies and chronic diseases are associated with perturbations from the homeostatic composition, and these transformations can lead to aberrant or deleterious tissue function. Spatial transcriptomics enables the concurrent measurement of gene expression and cell type composition, providing an opportunity to identify transcripts that co-vary with and potentially influence nearby cell composition. However, no method yet exists to systematically identify such intercellular regulatory factors. RESULTS/UNASSIGNED:Here, we develop Spatial Paired Expression Ratio (SPER), a computational approach to evaluate the spatial dependence between transcript abundance and cell type proportions in spatial transcriptomics. We demonstrate the ability of SPER to accurately detect paracrine drivers of cellular abundance using simulated data. Using publicly available spatial transcriptomics data from mouse brain and human lung, we show that genes identified by SPER show statistical enrichment for both extracellular secretion and participation in known receptor-ligand interactions, supporting their potential role as compositional regulators. Taken together, SPER represents a general approach to discover paracrine drivers of cellular compositional changes from spatial transcriptomics. AVAILABILITY AND IMPLEMENTATION/UNASSIGNED:The methods are implemented in R and available at: https://github.com/TianxiaoNYU/SPER.

PARP1 detection of DNA strand breaks allosterically leads to PARP1 synthesis of poly(ADP-ribose) modifications that signal DNA damage. HPF1 engages activated PARP1 to control modification site selection. Understanding of the mechanism of DNA break detection and catalytic activation is incomplete, due largely to limited structural information for full-length PARP1. Here, single-particle cryo-EM provides views of the full complement of PARP1 domains engaging a DNA single-strand break in the presence of HPF1 and a fragment of binding partner Timeless. Cryo-EM, single-molecule DNA dynamics, and small-angle X-ray scattering analysis indicate that PARP1 remains dynamic even when the multi-domain structure is organized on a DNA break, with the minimal catalytic region displaying high mobility relative to domains engaging damage. We propose that the organization of PARP1 domains on a DNA break releases a tethered, constitutively active catalytic region to modify molecules in a radius surrounding the DNA break site.

BACKGROUND/UNASSIGNED:Few studies have directly compared limitations in activities of daily living (ADLs) between reverse shoulder arthroplasty (RSA) and anatomic total shoulder arthroplasty (aTSA). This study evaluates ADL function at mid-term follow-up in patients with revision-free RSA and aTSA. METHODS/UNASSIGNED:This retrospective cohort study included 250 patients who underwent primary aTSA (n = 177) or RSA (n = 73) with a minimum follow-up of 7 years (mean 10 ± 2 years). Patients who had revision surgery were excluded. Multivariable ordinal logistic regression analysis was used to assess the odds of RSA patients reporting better ADL function compared to aTSA patients. RESULTS/UNASSIGNED:Postoperatively, a greater proportion of aTSA patients reported normal ADLs compared to RSA patients. On multivariable analysis, controlling for baseline differences, RSA patients reported lower ADL function for personal hygiene/toilet needs (Odds ratio [OR] 0.21 [95% CI: 0.07-0.65]; p = 0.006), washing/combing hair (OR 0.36 [0.13-1.02]; p = 0.049), putting on a button-up shirt (OR 0.08 [0.02-0.25]; p < 0.001), and putting on pants (OR 0.12 [0.03-0.39]; p < 0.001). DISCUSSION/UNASSIGNED:After adjusting for differences in baseline factors, RSA patients reported greater difficulty with specific ADL tasks-including toileting, personal hygiene, grooming, and dressing-compared to aTSA patients. LEVEL OF EVIDENCE/UNASSIGNED:Level III; Retrospective cohort study.

OBJECTIVES/OBJECTIVE:To examine (1) differences in low-value care (LVC) for common emergency conditions by race and ethnicity in US children's hospitals and (2) the association between hospital characteristics, including LVC rate, and the magnitude of within-hospital LVC differences by race and ethnicity. We hypothesized smaller LVC differences in hospitals with lower overall LVC rates. METHODS:We performed a cross-sectional study of children younger than 18 years discharged from the emergency department with asthma, bronchiolitis, headache, or minor head injury in the Pediatric Health Information System (PHIS) from January 2021 to June 2023. Exposures were patient race and ethnicity (non-Hispanic Black, "Black"; non-Hispanic white, "white"; Hispanic) and deidentified PHIS hospital. Outcomes were LVC by race and ethnicity within and across hospitals. We used multivariable logistic regression, reporting adjusted odds ratios (aORs) and 95% CI, to estimate hospital-level and condition-specific LVC differences and linear regression to examine the association between LVC differences and LVC rates. RESULTS:Among 314 138 eligible encounters, overall LVC rates were as follows: asthma 18%, bronchiolitis 32%, headache 24%, and minor head injury 26%. White compared with Black and Hispanic patients had higher odds of LVC across multiple conditions in pooled and within-hospital analyses. The largest pooled differences were for white vs Black: asthma aOR (95% CI) = 1.51 (1.18-1.95) and headache 1.57 (1.43-1.72). Hospital LVC rate was not associated with magnitude of within-hospital LVC difference for any condition. CONCLUSIONS:Lower hospital LVC rates were not associated with reduced LVC differences. Intentional focus on LVC differences is important when designing LVC reduction efforts.

OBJECTIVES/OBJECTIVE:To evaluate whether ultrasound-guided preoperative localization of soft tissue masses in the musculoskeletal system using a wireless radar reflector reduces operative times and reoperation rates compared to a control group referred by the same oncology team. METHODS:Retrospective review of SAVI SCOUT radar localizations performed preoperatively for soft tissue masses between 2021 and 2025. All imaging, clinical details, and operative times were evaluated. Comparison was made between the localized group and a control group matched for demographics (age and sex), comorbidities (American Society of Anesthesiologists score), location (trunk versus appendicular; subcutaneous versus deep/subfascial), histopathology (benign versus malignant), and case complexity (primary closure versus flap reconstruction). Cases were performed by the same oncological surgical team referred directly or via the multidisciplinary tumor board during the same time course. RESULTS:Twenty-four radar localized cases were compared with 24 control cases. Median case time in the SAVI SCOUT group was 52.0 minutes (interquartile range 38.0) and there was no significant difference in case times between the localized and control groups (p > .05). There were no reoperations in the localized group whereas 5 patients in the non-localized control group underwent reoperation for positive margins, though this difference fell short of statistical significance (p = .056). The most common lesions in the localized group were metastatic melanoma (12.5%) and intramuscular myxoma (8.3%), liposarcoma (8.3%), and metastatic leiomyosarcoma (8.3%). CONCLUSIONS:Preoperative localization demonstrated no substantial improvement in operative time compared to the non-localized group. However, re-resection rates were higher in the non-localized group.