Faculty Bibliography

Chronic exertional compartment syndrome (CECS) is a condition which involves sudden and painful increases in pressure of the musculofascial compartments of the lower leg in association with increased physical activity. A variety of surgical options, including endoscopic fasciotomy, exist to mechanically decompress the fascia. Recent progress in in-office needle endoscopy has shown potential for the diagnosis and treatment of various orthopaedic pathologies. We present the case of a 20-year-old collegiate sprinter with a 3-month history of CECS that was treated with bilateral in-office needle endoscopic 4 compartment fasciotomy. The patient was able to return to his previous level of competition 8 weeks postoperatively, and there were no complications. To the authors' knowledge, this is the first report of an in-office endoscopic 4-compartment fasciotomy for the management of CECS.Levels of Evidence: V, case report.

Adhesive small bowel obstruction (ASBO) is a common surgical emergency, most frequently caused by postoperative adhesions. Although many patients improve with bowel rest, nasogastric decompression, intravenous fluids, and electrolyte correction, delayed operative intervention in patients unlikely to resolve nonoperatively can increase morbidity. Water-soluble contrast (WSC) agents such as Gastrografin, Urografin, and related diatrizoate preparations have been proposed as diagnostic, prognostic, and potentially therapeutic adjuncts. In this article, we review the available clinical evidence on the use of WSC in adult adhesive or postoperative small bowel obstruction (SBO) and examine whether its primary role is diagnostic and prognostic rather than therapeutic. A structured narrative review was conducted in accordance with PRISMA guidelines, using studies identified through PubMed, Excerpta Medica database (Embase), and manual searches. Eligible studies included adult patients with adhesive, postoperative, or non-strangulated SBO who received oral or nasogastric WSC and reported clinical outcomes such as passage of contrast, obstruction resolution, operative intervention, hospital length of stay, or complications. Randomized trials, prospective observational studies, retrospective cohort studies, and protocol evaluations were included. Due to differences in study design, patient populations, contrast protocols, and outcome definitions, the findings were synthesized narratively. Twenty-one primary clinical studies met the inclusion criteria and were included in the review. Several studies demonstrated faster resolution of obstruction, shorter hospital stays, and lower rates of surgery. However, other studies did not show significant improvements in these outcomes. These discrepancies are likely due to differences in study design, patient selection, timing of contrast administration, and variations in WSC challenge protocols. In contrast, the prognostic value of WSC was consistent across studies, as the progression of contrast to the colon was reliably associated with successful nonoperative management. Overall, the evidence suggests that the primary value of WSC lies in its diagnostic and prognostic roles, while its therapeutic benefit remains uncertain.

OBJECTIVE:Epidemiologic estimates for age of systemic lupus erythematosus (SLE) diagnosis are limited, particularly for men and racial and ethnic subpopulations in the United States. Leveraging the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population-based SLE registries, meta-analyses were performed estimating age-specific incidence of SLE by sex, race, and ethnicity. METHODS:The CDC network of SLE registries includes five state-based registries, plus a sixth Indian Health Service registry. Incidence periods spanned calendar years 2002-2018. Registries provided age-specific incidence of SLE, fulfilling the American College of Rheumatology (ACR) SLE classification criteria, per 100,000 person-years, stratified by sex, race, and ethnicity for the meta-analyses. RESULTS:Incidence rates among women were highest for those aged 30-39 (12.7, 95%CI: 9.5-16.8), while rates among men were highest for those aged 60-69 (2.1, 95%CI: 1.3-3.4). Black women aged 20-39 had the highest SLE incidence rates (23.6, 95%CI: 20.7-26.8). Among women diagnosed with SLE before age 20, incidence was highest among Asian (6.5, 95%CI: 2.8-15.2) individuals. Among women diagnosed with SLE after age 60, incidence was highest among American Indian/Alaska Native (9.4, 95%CI: 3.4-15.4) individuals. Weighted percentages show 10.0% of those with SLE were diagnosed before age 20, while 15.1% were diagnosed after age 60. The largest proportion of individuals with SLE, 22.1%, were diagnosed between 30-39 years. CONCLUSIONS:This study provides comprehensive sex- and race-specific estimates of age at SLE diagnosis. The substantial later in life SLE incidence among men and disease burden in pediatric and older populations should raise awareness in considering SLE in the differential diagnosis in previously underrecognized groups.

OBJECTIVE:Neutrophil dysfunction is a hallmark of systemic lupus erythematosus (SLE), but its molecular basis remains unclear. This study explores transcriptional and posttranscriptional changes in low-density granulocytes (LDGs), a proinflammatory neutrophil subset expanded in SLE, focusing on NADPH oxidase (Nox) function and minor intron splicing. METHODS:) expression was evaluated at transcript and protein levels. Nox activity was measured using luminol assays. Bulk RNA sequencing (RNA-seq) and rMATS software were used to assess alternative splicing, particularly of U12-type intron-containing genes. RESULTS:CYBA expression was reduced in SLE LDGs (n = 11) compared to SLE and HC NDGs (n = 6), with levels resembling those in chronic granulomatous disease neutrophils. SLE LDGs exhibited impaired Nox activity (n = 7 SLE, n = 12 HC). CYBA is a U12 intron-containing gene, and transcriptomic analysis revealed broad down-regulation of this gene class in SLE LDGs, suggesting minor spliceosome dysfunction. rMATS analysis showed increased U12-type intron retention and widespread splicing defects-including exon skipping and mutually exclusive exon use-in genes such as GBP5, MAEA, and STX10. These abnormalities were validated in an independent long-read RNA-seq data set from SLE peripheral blood mononuclear cells. Importantly, splicing disruptions correlated with disease activity and autoantibody profiles. CONCLUSION/CONCLUSIONS:Impaired U12-dependent splicing may contribute to neutrophil dysfunction in SLE, potentially via defective oxidative burst and altered immune regulation. These findings highlight the minor spliceosome as a novel player in lupus pathogenesis.

PURPOSE/OBJECTIVE:Clinical guidelines for interpreting genetic variants in the context of Mendelian disease require converting the outputs of pathogenicity prediction tools into well-calibrated probabilities. However, the existing calibration method is only valid when pre-committing to one tool, preventing clinical laboratories from using multiple tools with complementary strengths. To lift this restriction, we introduce Pathogenicity K-Nearest Neighbors (P-KNN), a flexible method that jointly calibrates any set of tools. METHODS:P-KNN represents each variant in a multidimensional space defined by tool scores and estimates the probability of pathogenicity based on the proportion of pathogenic neighbors. We compared P-KNN against standard single-tool calibration of multiple predictors and meta-predictors at four historical time points. RESULTS:P-KNN outperforms standard calibration of single tools and meta-predictors in two aspects: i) overall evidence strength and ii) alignment of the calibrated probabilities with true pathogenicity frequencies. Additionally, the evidence from P-KNN keeps improving with the addition of newer tools. It also correctly integrates correlated computational and experimental evidence that is overestimated by existing protocols. CONCLUSION/CONCLUSIONS:P-KNN provides robust joint calibration for any set of pathogenicity prediction tools, thereby alleviating the constraint of pre-committing to a single predictor while enhancing statistical rigor and diagnostic yield. P-KNN is available via command line (https://github.com/Brandes-Lab/P-KNN) and precomputed scores (https://huggingface.co/datasets/brandeslab/P-KNN).

IMPORTANCE:As long-term survival after solid organ transplant has improved, malignant neoplasms have emerged as a major determinant of outcomes. OBJECTIVES:To examine whether posttransplant cancer risk follows uniform trajectories over time or exhibits patterns across organ types and malignant neoplasm subtypes. DESIGN, SETTING, AND PARTICIPANTS:This population-based cohort study used US nationwide data from 2000 to 2023 from the United Network for Organ Sharing registry. Participants were first-time recipients of heart, lung, liver, or kidney transplant. Analyses were conducted from March to June 2026. MAIN OUTCOMES AND MEASURES:Incidence rates of first-occurring cancers for each cancer subtype were estimated per 100 person-years across 1-year intervals during the first decade after transplant. Temporal changes were evaluated using Poisson regression models adjusted for attained age, sex, transplanted organ type, and calendar period. RESULTS:Among 622 330 transplant recipients (60 268 heart, 42 755 lung, 146 852 liver, and 372 455 kidney; median [IQR] age, 53 [41-61] years; 389 794 [62.6%] male), nonmelanoma skin cancers accounted for 30 049 of 54 709 cancers (54.9%). Lung, heart, and liver transplant recipients had consistently higher cancer incidence rates than kidney transplant recipients (eg, solid organ cancer: heart transplant: incidence rate ratio [IRR], 1.57 [95% CI, 1.51-1.63]; lung transplant: IRR, 2.01 [95% CI, 1.92-2.09]; liver transplant: IRR, 1.19 [95% CI, 1.14-1.22]). These differences increased with time since transplant for lung and heart transplant recipients (eg, solid organ cancer among heart vs kidney transplant recipients: year 1: IRR, 0.94 [95% CI, 0.83-1.07]; years 2-5: IRR, 1.54 [95% CI, 1.45-1.64]; years 6-10: IRR, 1.86 [95% CI, 1.75-1.98]). Three general temporal patterns were observed: an early peak followed by a decline for selected malignant neoplasms (including posttransplant lymphoproliferative disease and thyroid cancer), relatively stable rates for several cancer types, and progressively increasing incidence rates over time for selected solid organ malignant neoplasms (including lung, bladder, colorectal, and genital cancers). These patterns persisted after multivariable adjustment. CONCLUSIONS AND RELEVANCE:In this cohort study of solid organ transplant recipients, cancer incidence rates demonstrated distinct time-dependent patterns that varied by malignant neoplasm subtype and transplanted organ. These findings describe time-dependent risk trajectories among transplant survivors and may inform the timing of surveillance strategies and future studies of cancer risk in this population.

PURPOSE/OBJECTIVE:To describe two recurrent phenotypes of retinal pigment epithelium (RPE) defects, sealed and unsealed, which may occur in various diseases. METHODS:Medical records and multimodal imaging of 17 patients (70.3 ± 9.3 years) with RPE defects, including RPE apertures, RPE detachment (RPED) devoid of RPE, and serous maculopathy with the absence of RPE (SMARPE), were retrospectively analyzed. Proposed pathogenic mechanisms are presented, revising current terminology. RESULTS:Eyes with RPE apertures (12/17, 70.6%) and SMARPE (1/17, 5.9%) presented RPE defects connecting the subretinal and sub-RPE spaces with subretinal fluid (SRF) and intact outer retina. These features are consistent with patent RPE defects, termed 'unsealed'. RPED devoid of RPE defects developed in ¾ eyes (75%) over a serous PED without collapse. The lesions occurred beneath a degenerated outer retina that adheres to the RPE defect without SRF, supporting the term 'sealed'. CONCLUSIONS:RPE defects beneath a disrupted photoreceptor layer may become "sealed" by reactive Müller cell gliosis, preventing the occurrence of SRF. RPE defects with intact photoreceptors remain "unsealed", resulting in SRF accumulation. We propose "sealed" and "unsealed" as disease agnostic terms, which can be used for cases previously described as "RPE aperture," "SMARPE," and "RPED devoid of RPE".

BACKGROUND AND AIMS/OBJECTIVE:Absolute risk estimates of serious infections in inflammatory bowel disease (IBD) across therapies and concomitant corticosteroid treatment are limited. We aimed to assess serious infection risk in IBD patients receiving different therapies, with or without corticosteroids. METHODS:Using nationwide Swedish registers (2007-2024), we compared rates of serious infections in patients with IBD treated with different therapies versus matched population comparators (≤10 per patient), stratified by corticosteroid use. We also performed 1:1 propensity score (PS)-matching for direct comparison of infection risk in IBD with or without concomitant corticosteroids exposure across advanced therapies. Incidence rates and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated. RESULTS:We identified 145,125 exposure periods in patients with IBD naïve to immunomodulators and advanced therapies, 82,675 to immunomodulators, and 90,181 to advanced therapies (TNF inhibitors with and without immunomodulator, anti-integrins, anti-interleukins, and JAK inhibitors). Across therapies, exposure periods with corticosteroids carried a higher risk of serious infections than periods without, both compared to the general population (incidence rate difference range=3.6-10.2/100 person-years; aHR range=4.52-15.86) and in PS-matched within therapy group comparisons (incidence rate difference range=3.9-8.5/100 person-years; aHR=1.82-3.60). Relative risk was highest in children and increased with cumulative corticosteroid dose. CONCLUSION/CONCLUSIONS:Patients with IBD receiving corticosteroids had significantly higher rates of serious infections compared with those not receiving corticosteroids across therapies, with rate differences across age groups and combinations of treatments. These data will inform infection risk assessment and consideration of individualized infection-prevention strategies.