Faculty Bibliography

BACKGROUND:Some pulse oximeters perform worse in people with darker skin, and this may be due to inadequate diversity of skin pigment in device development study cohorts. Guidance is needed to accurately and equitably characterize skin pigment to ensure diversity in research cohorts. We tested multiple methods for characterizing skin pigment to assess comparability and impact on cohort diversity. OBJECTIVES/OBJECTIVE:Assess reliability and comparability of common skin pigment measurement methods Compare findings from different anatomical sites Demonstrate that pigment cannot be assumed from US National Institutes for Health (NIH) race categories. METHODS:We used three subjective methods (perceived Fitzpatrick pFP, Monk Skin Tone MST and Von Luschan VL) and two objective methods (Konica Minolta CM-700d spectrophotometer and Delfin Skin Color Catch DSCC colorimeter) for individual typology angle (ITA), across multiple measurement sites in adults. We calculated ΔE to estimate operator perceptibility thresholds for subjective methods and to determine reproducibility for objective methods. We used each method to categorize participants as 'light, medium, or dark' and compared the impact of method selection on cohort diversity. RESULTS:We studied 789 participants, with 33,856 assessments. The MST had the widest luminosity range, and VL had the least discernible adjacent categories. With 'dark' defined as ITA <-30°, 14% of participants were categorized 'dark' as compared to 26% by pFP or 16% by MST. Approximately half of the 'dark' cohort had an ITA <-50°. With an ITA threshold <-50°, only 7% of the cohort was categorized as 'dark.' When 'Black or African American' self-identification was used to define 'dark', 23% of the cohort was categorized as such. Each self-assigned NIH race category included a wide range of ITA and subjective scale categories. Both ITA and L* from the KM-700d and DSCC demonstrated strong correlation (⍴ > 0.7). CONCLUSION/CONCLUSIONS:Common methods for skin pigment characterization, especially the use of race or subjective scales, have significant limitations. When applied to the same cohort, different methods yield significantly different results, and some may overestimate diversity. Previously published ITA thresholds for defining 'dark' skin are too light and lead to underrepresentation of people with darker skin.

BACKGROUND AND PURPOSE/OBJECTIVE:Accurate localization of the ventral intermediate nucleus (VIM) within the dentatorubrothalamic tract (DRTT) is critical for effective neurosurgical treatment of essential tremor (ET). This study evaluated the feasibility and anatomical specificity of quantitative susceptibility mapping (QSM) for direct VIM/DRTT visualization, comparing it with conventional diffusion tractography-based reconstructions. MATERIALS AND METHODS/METHODS:Twenty-seven participants (10 healthy controls, 17 ET patients) were enrolled across two institutions and imaged on 3T MRI systems. QSM-defined VIM/DRTT regions were manually segmented based on characteristic hypointense susceptibility contrast. Whole-brain diffusion tractography was performed to reconstruct the DRTT, pyramidal tract (PT), and medial lemniscus (ML) tracts. Spatial overlap between QSM-and tractography-defined VIM/DRTT regions was calculated, as well as overlap with neighboring PT and ML tracts to assess specificity. RESULTS:Two participants were excluded due to insufficient VIM/DRTT streamlines in tractography reconstruction. In healthy controls, QSM-and tractography-defined VIM/DRTT showed high spatial correspondence (left: 87.6 ± 5.1%; right: 85.3 ± 6.5%). ET patients exhibited slightly lower overlap (mean range: 71.5 - 85.1%). Overlap with neighboring PT and ML tracts was minimal (<3.3%), confirming high anatomical specificity of QSM-derived VIM/DRTT regions. CONCLUSIONS:QSM enables direct visualization of the VIM/DRTT with high spatial agreement to conventional tractography-based approaches while demonstrating minimal overlap with adjacent tracts. These findings support QSM as a complementary or standalone imaging modality for improved, patient-specific neurosurgical targeting in ET. ABBREVIATIONS/BACKGROUND:DBS = deep brain stimulation; DRTT = dentatorubrothalamic tract; ET = essential tremor; ML = medial lemniscus; MRgFUS = MR-guided focused ultrasound; VIM = ventral intermediate nucleus; PT = pyramidal tract; QSM = quantitative susceptibility mapping; WM = white matter.

OBJECTIVE:The CDC recommends initiating opioids for pain treatment at the lowest effective dose and duration. We examine how interactions between dose, duration, and other medication factors (e.g., drug type) influence opioid use disorder (OUD) risk-a gap not considered by CDC guidelines. SUBJECTS/METHODS:Using Medicaid claims data (2016-2019) from 25 states, we analyzed opioid-naïve adults, newly diagnosed with musculoskeletal pain who initiated opioids within three months of diagnosis. A 6-month washout confirmed no prior opioid exposure or musculoskeletal diagnosis. METHODS:Initial opioids were categorized by "dose-days supplied" (low [>0-20 mg MME] to very high [>90 mg MME] dose, and short [1-7 days] to moderate [>7-30 days] supply), and by opioid type; physical therapy (PT) sessions were also recorded. Using Poisson regression models, we estimated the OUD risk associated with dose-days categories, adjusting for baseline demographics, clinical characteristics, and medications. We separately examined opioid dose-days and PT, and assessed PT's moderating effect on dose-days' impact. RESULTS:Among 30,536 patients, half initiated opioids at 20-50 MME for 1-7 days, and 20% received PT. OUD risk was 2-3 times higher for opioids initiated for >7-30 days compared to 1-7 days across doses, and 5.5 times higher for opioids initiated for >7-30 days at > 90 MME versus 1-7 days at < 20 MME. PT alone, neither affected OUD risk nor mitigated the increased risk from longer or higher-dose opioids. CONCLUSIONS:Our findings support the need for careful opioid prescribing and alternative pain management strategies, as the observed associations between initial prescription characteristics and OUD were not mitigated by adjunctive PT. PERSPECTIVE/CONCLUSIONS:This study demonstrated that initial opioid prescriptions of 7-30 days, especially above 90 MME/day, increased OUD risk in opioid-naïve patients with musculoskeletal pain; physical therapy did not mitigate the risk. Different opioids posed varied risks, even at the same dose and duration. Careful prescribing and alternative pain management are essential.

INTRODUCTION/BACKGROUND:Chinese Americans are one of the fastest growing racial and ethnic groups and represent the largest subgroup of the Asian American population in the US and in New York City (NYC) where they number 573,528 in 2021. Despite their numbers, current pain perceptions, expectations, and attitudes of Chinese Americans remains poorly understood, especially as related to postoperative pain. OBJECTIVE:A better understanding of pain experience among Chinese American patients is needed to inform strategies on improving pain management satisfaction. METHODS:A total of 27 Chinese American postoperative patients from a NYC health system were recruited for face-to-face surveys and interviews with a trained bilingual and bicultural Community Health Worker. Questions from the Survey on Disparities in Quality of Healthcare and Kleinman's Explanatory Model of Illness were integrated into the survey and topic guide. Topics of discussion included satisfaction with healthcare and pain management during hospital stay and health beliefs and practices. RESULTS:More than half of participants experienced language challenges that made it difficult to communicate with healthcare staff. In general, high levels of satisfaction with pain management were reported; however, participants reported feeling less comfortable asking healthcare teams questions. Common themes across interviews included: (1) pain was an expected outcome of the procedure and was thus perceived as tolerable; (2) the wish to not be a burden to others; (3) concerns about side effects of pain medications; and (4) a cultural and language mismatch between healthcare teams and patients on words being used to elicit pain and discomfort. CONCLUSION/CONCLUSIONS:Our project findings can inform pain management strategies and tools to serve the Chinese American patient population.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Only a minority of renal oncocytic tumors are aggressive. These tumors' behavior is difficult to predict by histopathological evaluation; consequently, many patients experience anxiety upon diagnosis and may undergo unnecessary treatment. Our aim was to derive genomic and epigenomic signatures to distinguish clinically indolent renal oncocytic tumors from aggressive chromophobe renal cell carcinoma (ChRCC). METHODS:We performed molecular profiling of nephrectomies from 68 patients: 44 with indolent renal oncocytic tumors (19 renal oncocytoma, two oncocytic renal neoplasm of low malignant potential, and 23 indolent ChRCC) and 24 with aggressive ChRCC. We performed targeted exome sequencing, gene expression profiling, and whole-genome methylation sequencing of formalin-fixed, paraffin-embedded (FFPE) samples. We also analyzed The Cancer Genome Atlas Kidney Chromophobe data from 66 ChRCC patients in silico. Genomic and epigenomic signatures linked to aggressive ChRCC-obtained from sampling morphologically nonsarcomatoid foci-from both cohorts were derived using the least absolute shrinkage and selection operator method. KEY FINDINGS AND LIMITATIONS/UNASSIGNED:Aggressive ChRCC was distinguished from indolent ChRCC and other indolent renal oncocytic tumors using a focused seven- to 11-gene expression signature (ten-fold cross-validation [CV] area under the curve [AUC] = 0.77-0.85) with an external validation AUC of 0.88, and an eight-CpG methylation signature (ten-fold CV AUC = 0.86) with an external validation AUC of 0.91. TP53 and PTEN mutations substantially increased the probability of aggressive ChRCC. Limitations include the small sample size. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:Focused genomic and epigenomic signatures from routinely processed FFPE tumor tissues can help distinguish aggressive ChRCC from indolent renal oncocytic tumors, including indolent ChRCC. This forms the basis for replication studies to inform appropriate patient management, provide reassurance, and guide follow-up.

INTRODUCTION/BACKGROUND:Chronic pain is associated with sleep disturbances, with >70% of patients reporting clinically significant insomnia. Although dorsal root ganglion stimulation (DRGS) is an established therapy for focal neuropathic pain, its impact on sleep has not been well characterized. This study evaluated changes in patient-reported insomnia after DRGS and examined associations among sleep, pain, and functional outcomes. MATERIALS AND METHODS/METHODS:We retrospectively analyzed patients from a prospective DRGS registry treated between 2018 and 2025. Patients with baseline Insomnia Severity Index (ISI) scores ≥8 and ≥one follow-up were included. Secondary outcomes included pain intensity (numerical rating scale, NRS), disability (Oswestry Disability Index, ODI), and health-related quality of life (EQ-5D). Spearman's rank correlation was used to assess relationships between ISI changes and other outcome measures. RESULTS:Overall, 92 patients were included with a mean follow-up of 26.8 months. At final follow-up (range 3-60 months), mean (SD) ISI improved from 20.5 to 9.8 (-10.8 ± 9.9; -52.5%), ODI from 63.9 to 30.4 (-33.5 ± 17.7; -52.5%), NRS from 9.0 to 4.2 (-4.9 ± 2.1; -53.9%), and EQ-5D from 0.34 to 0.74 (+0.40 ± 0.21; +116.1%). The proportion of patients with moderate or severe insomnia decreased from 79% to 14%, with 59% (n = 54) reporting no clinically significant insomnia. ISI improvement correlated most with reductions in disability (ρ = 0.39; p < 0.0001) and only weakly with pain reduction (ρ = 0.19; p = 0.070). CONCLUSIONS:DRGS was associated with substantial and sustained improvements in sleep among patients with chronic pain with baseline insomnia. Robust improvements were observed in ODI, EQ-5, visual analog scale, and ISI that were maintained over time. Our findings suggest that sleep-related benefits are more closely tied to functional improvement than to pain relief, supporting a broader therapeutic role for DRGS.

Clinical decision-making often simplifies continuous risk data into discrete levels using round-number thresholds. These simplifications can distort risk assessments. To systematically uncover these distortions, we develop an interpretable machine learning model that identifies anomalies caused by threshold-based practices. Through simulations, real-world data, and longitudinal studies, we demonstrate how round-number thresholds can lead to discontinuities and counter-causal paradoxes in mortality risk. Despite advances in medicine, these anomalies persist, underscoring the need for dynamic and nuanced risk assessment methods in healthcare. Our findings suggest continuous reassessment of clinical protocols, especially in critical settings like intensive care, to improve patient outcomes by aligning thresholds with the continuous nature of risk.

Xenotransplantation of genetically-modified pig kidneys offers a solution to the scarcity of organs for end-stage renal disease patients.¹ We performed a 61-day alpha-Gal knock-out pig kidney and thymic autograft transplant into a nephrectomized brain-dead human using clinically approved immunosuppression, without CD40 blockade or additional genetic modification. Hemodynamic and electrolyte stability and dialysis independence were achieved. Post-operative day (POD) 10 biopsies revealed glomerular IgM and IgA deposition, activation of early complement components and mesangiolysis with stable renal function without proteinuria, a phenotype not seen in allotransplantation. On POD 33, an abrupt increase in serum creatinine was associated with antibody-mediated rejection and increased donor-specific IgG. Plasma exchange, C3/C3b inhibition and rabbit anti-thymocyte globulin (rATG), completely reversed xenograft rejection. Pre-existing donor-reactive T cell clones expanded progressively in the circulation post-transplant, acquired an effector transcriptional profile and were detected in the POD 33 rejecting xenograft prior to rATG treatment. This study provides the first long-term physiologic, immunologic, and infectious disease monitoring of a pig-to-human kidney xenotransplant and indicates that pre-existing xenoreactive T cells and induced antibodies to unknown epitope(s) present a major challenge, despite significant immunosuppression. It also demonstrates that a minimally gene-edited pig kidney can support long-term life-sustaining physiologic functions in a human.

The management of drug-resistant epilepsy (DRE) in the pediatric population using neurostimulation of the centromedian (CM) nucleus of the thalamus (CMN) has been reported to be effective and safe. We present a case series of pediatric patients treated with responsive neurostimulation (RNS) and report on contact localization in relation to preliminary outcomes, specifically seizure reduction rates. Thirteen pediatric patients treated with RNS underwent direct targeting of the CMN based on Magnetization-Prepared 2 Rapid Gradient-Echo (MP2RAGE) scans, using ClearPoint neuronavigation. The implanted electrodes were co-registered to a probabilistic anatomical model of the thalamic nuclei (Freesurfer) for secondary confirmation of contact localization. Ten out of the 12 patients with extra-temporal multifocal or generalized DRE (83.3%) had over 50% reduction in seizures, benefiting from an 80.4% seizure reduction rate. The average follow-up interval was 25.2 months, with no patients experiencing stimulation-related side effects. The analysis of post-operative images revealed that out of the 24 CM-processed electrodes, 23 (95.8%) had at least two contacts in the nucleus, based on patient-specific segmentation of the thalamus. The preliminary outcomes suggest a robust response to central neurostimulation and no stimulation-related side effects in pediatric patients suffering from multifocal or generalized DRE when implementing high-accuracy direct targeting. PLAIN LANGUAGE SUMMARY: We are reporting our experience in the management of the most challenging types of pediatric epilepsy, involving seizures originating from multiple and/or poorly defined brain areas. We surgically implanted a responsive neurostimulation device (RNS) in central areas of the brain that function as connection hubs between different brain regions. These devices are designed to detect early signs of abnormal brain activity, and respond with electrical pulses to prevent progression to clinical seizures. Using our approach, we reduced the seizure rates by an average of 80% in 83% of the pediatric patients who received this treatment.