Faculty Bibliography

INTRODUCTION/BACKGROUND:Patient and arteriovenous malformation (AVM) characteristics that portend success after treatment for low-grade brain AVMs remain unknown. PATIENTS AND METHODS/METHODS:We utilised the MISTA multicentre registry to identify patients with Spetzler-Martin (SM) grade I or II AVMs treated with stand-alone curative-intent intervention (resection, stereotactic radiosurgery [SRS] or endovascular embolisation). Bivariate and multivariable analyses were performed to identify patient and AVM characteristics predictive of complete obliteration or favourable outcome (complete obliteration without new permanent deficit or post-treatment haemorrhage). RESULTS:A total of 522 patients were included (292 microsurgery, 152 SRS, 78 embolisation). Complete obliteration rates differed between microsurgery (95.9%), SRS (75.0%) and embolisation (71.8%) (P < .001); among patients classified as cured, digital subtraction angiography (DSA) confirmed obliteration in 96.1%, 75.9% and 52.4%, respectively. Favourable outcome was achieved in 89.4%, 64.5% and 67.9% (P < .001). In adjusted models for obliteration, elderly age (odds ratio [OR] 0.49, P = .022), larger nidus (OR 0.64, P = .005) and compacted morphology (OR 1.93, P = .019) were independent predictors overall; paediatric age predicted incomplete obliteration after microsurgery (OR 0.05, P = .045), and elderly age (OR 0.19, P = .001) and larger nidus (OR 0.59, P = .015) after SRS. For favourable outcome, SM grade II overall (adjusted OR [aOR] 0.58, P = .031) and elderly age after SRS (aOR 0.31, P = .019) were independent negative predictors. DISCUSSION/CONCLUSIONS:Low-grade AVMs showed high rates of complete obliteration, though DSA-confirmed rates were substantially lower after embolisation, underscoring the importance of angiographic confirmation. CONCLUSION/CONCLUSIONS:The predictors identified in this study may help guide management when 2 or 3 of the primary treatment options carry clinical equipoise.

Chromatin-modifying complexes are critical in gene regulation, yet their proposed interactions with RNA remain poorly understood. Counter to prior models of specific recruitment, we find that WDR5, an essential subunit of the MLL1/KMT2A histone methyltransferase complex, binds RNA promiscuously. Using a stringent approach, we demonstrate that WDR5 directly engages a diverse pool of cellular RNAs, dictated primarily by RNA abundance rather than specific motifs. Equilibrium binding assays show that RNA length, rather than sequence, governs high affinity. WDR5 binds to RNA through multiple surfaces, some of which overlap with MLL1 complex subunit interfaces. Strikingly, we find that RNA binding disrupts the MLL1 complex by competitively displacing WDR5 from these critical protein-protein interactions, leading to a marked inhibition of MLL1 catalytic activity. Further experiments in human cell lines suggest that this disassembly mechanism may operate to homeostatically downregulate MLL1 complex activity, thereby integrating transcriptional activity with chromatin state.

Surgical volumes continue to shift from inpatient and hospital outpatient departments to independent and co-owned Ambulatory Surgery Centers (ASCs). Consumer preferences, payer pressure, lower cost, possibility of site-neutral payments, equivalent safety, and clinical innovation have caused this outmigration. Physicians have embraced the shift due to dissatisfaction with current employment models, more professional autonomy, a sense of purpose, the ability to drive efficiency and quality of care, and the option to invest and benefit financially. Vascular surgeons can utilize their existing experience delivering outpatient care to grow their practices. The unique challenges and business structure of this care model, regulatory roadblocks, arbitrary reimbursement adjustments, and new corporate entrants to ASCs need to be understood. New models of outpatient care will likely include shifting higher-acuity procedures to ASCs. The care will be delivered by independent vascular surgeons or through alignment between physicians and hospital systems to provide optimal care to patients in convenient, secure, and cost-effective settings.

Exposure to World Trade Center (WTC) dust following the September 11, 2001 attacks has been linked to numerous negative health outcomes in First Responders, including cognitive impairment disproportionately impacting First Responders with aging. However, the mechanisms underlying neurocognitive decline remain poorly characterized. This investigation examined the effects of WTC dust exposure on myelin integrity and neuroinflammatory signaling in twelve-week old male spontaneously hypertensive rats. To model Ground Zero exposure in First Responders, WTC dust was intratracheally administered for two consecutive days (2.43 [± 0.78] mg/day).  It was hypothesized that WTC dust exposure would enhance neuroinflammatory signaling and promote an earlier, progressive decline of myelin abundance. Rats were euthanized at 3 and 12 mo post-exposure. Changes in myelin abundance (Black-Gold II), myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), and microglial responses (ionized calcium-binding protein; Iba1) were assessed through immunohistochemical staining, and cytokines were measured in brain homogenates. WTC dust exposure resulted in increased Black-Gold II staining at 3 mo despite no changes in MBP or CNPase. In contrast, microglial activation and IL-1β concentrations were elevated in dust-exposed rats at 12 mo. Collectively, these data suggest WTC dust exposure induces sustained neuroinflammatory signaling and may elicit a compensatory myelin response indicative of early neurodegeneration.

BACKGROUND:Tissue-based gene expression assays provide prognostic information in prostate cancer, but their influence on decisions regarding immediate treatment versus conservative management, including active surveillance (AS) and watchful waiting (WW), remains uncertain. METHODS:Using a linkage with the Surveillance, Epidemiology, and End Results program, we evaluated the association between a 22-gene genomic classifier (GC) and initial management among patients with low or intermediate clinical-risk prostate cancer diagnosed from 2015 through 2018. Initial management was classified as immediate therapy or AS/WW, and GC scores were grouped as low (<0.45), intermediate (0.45-0.60), or high (>0.60). Multivariable logistic regression assessed associations between GC category and immediate treatment, stratified by clinical-risk group and adjusted for demographic and clinical covariates. RESULTS:Among 2,547 patients, 286 of 1,030 (27.8%) with low- and 1,113 of 1,517 (73.4%) with intermediate clinical-risk prostate cancer received initial treatment. Use of initial treatment increased with higher GC category. Among patients with low and intermediate clinical-risk prostate cancer, respectively, 20.5% and 57.5% with low GC, 28.3% and 75.8% with intermediate GC, and 46.2% and 88.3% with high GC scores received initial treatment. Higher GC category was independently associated with greater odds of immediate treatment versus AS/WW (versus low GC: intermediate GC, odds ratio [OR] 1.98, 95% confidence interval [CI] 1.57-2.49, p < 0.001; high GC, OR 4.42, 95% CI 3.41-5.71, p < 0.001). CONCLUSIONS:Higher GC scores were associated with greater use of immediate treatment and less use of AS/WW, underscoring the need to determine whether GC testing also predicts long-term outcomes among patients managed with AS.

Gluteal tendon tears are typically degenerative and often only partial. For patients who fail nonoperative management, endoscopic repair is a reasonable option. Traditionally, a knotted side-to-side suture repair technique has been used, though this can be technically demanding and leave knot stacks adjacent to the trochanteric bursa. Using a suture staple technique may increase the tendon-footprint contact area and avoids the knot stacks. Although the biomechanics seem theoretically in favor of the staple technique, this has yet to be proven. Clinically, the techniques are likely comparable, though more research is needed on several fronts before a determination can be made.

OBJECTIVE:To quantify general population prevalence, and differences by sex and BMI, in ultrasound (US) features of knee osteoarthritis (KOA), patient-reported knee symptoms (Ksx), radiographic KOA (rKOA), and symptomatic KOA (sxKOA). METHODS:Participants from the Johnston County Health Study (2019-2024; n=902) provided demographic, clinical, and imaging data. Ksx was defined as self-reported pain, aching or stiffness on most days of any one month in the past 12 months. rKOA was defined as Kellgren-Lawrence grade ≥2 (or total knee replacement (TKR)), severe rKOA as grades 3-4 (or TKR), and sxKOA as rKOA and Ksx in the same knee. Standardized US scoring was performed as previously reported. Weighted prevalence estimates and 95% confidence intervals (CI) for Ksx, rKOA, sxKOA, severe rKOA, and US features were calculated overall and by sex and BMI category. RESULTS:Among 902 participants (67% female; 66% non-Hispanic white, mean age 55 years, and BMI 33 kg/m²), the weighted prevalence of Ksx, rKOA, sxKOA, and severe rKOA were 61%, 36%, 27%, and 21%, respectively, all higher (based on non-overlapping CIs) than baseline estimates from the Johnston County Osteoarthritis Project and other cohorts. Ksx, rKOA, sxKOA, and severe rKOA were higher among females and those with obesity. Compared to females with obesity, those with severe obesity had higher prevalence of all radiographic outcomes at moderate and severe grades with non-overlapping CI. US effusion and synovitis were more prevalent in males, whereas medial and lateral cartilage damage were more common in females. With increasing obesity, osteophytes and medial cartilage damage were more prevalent, while gryescale effusion was actually less frequent. CONCLUSION/CONCLUSIONS:KOA prevalence continues to increase in the population. Sex and BMI differences in KOA prevalence and US features were most pronounced among females with severe obesity. Distinguishing between sexes and by obesity levels may improve understanding of KOA mechanisms and guide tailored prevention and treatment strategies.

BACKGROUND/UNASSIGNED:Acute kidney injury (AKI) may worsen outcomes of delirium tremens (DT), but data are limited. We investigated the association between AKI and hospital outcomes in DT and identified factors associated with AKI. METHODS/UNASSIGNED:We conducted a retrospective observational study using the National Inpatient Sample (2017-2022) and ICD-10 codes. Adult hospitalizations with a principal diagnosis of DT were identified and stratified by AKI as a secondary diagnosis. Primary outcomes were endotracheal intubation rate, hospital length of stay, and all-cause hospital mortality. Multivariate regression, inverse probability of treatment weighting, and augmented inverse probability weighting were performed. RESULTS/UNASSIGNED: < 0.001). These findings were consistent after weighting analyses. AKI was associated with male sex, Black race, sepsis, obesity, and higher Charlson Comorbidity Index. CONCLUSIONS/UNASSIGNED:AKI is common among patients hospitalized with DT and is associated with worse hospital outcomes.

IMPORTANCE:There are 3.5 million prostate cancer survivors in the US, with a need for evidence-based lifestyle recommendations that improve survivorship. OBJECTIVE:To assess whether consumption of specific dietary fats after diagnosis is associated with long-term survival among patients with nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS:This study, nested in the Health Professionals Follow-Up Study, a cohort of male health professionals from across 50 US states ongoing since 1986, included participants with confirmed nonmetastatic prostate cancer between 1986 and January 2019, followed up through December 2022. Statistical analysis was conducted from July 2024 to May 2026. EXPOSURES:Dietary data were collected every 4 years from validated food frequency questionnaires and used to estimate intake of saturated, polyunsaturated, monounsaturated, trans, plant, and animal fat after cancer diagnosis. MAIN OUTCOMES AND MEASURES:Main outcomes were all-cause mortality and death from prostate cancer, other cancers, cardiovascular disease, and other causes during a median 12.8 years (IQR, 8.1-16.8 years) of follow-up through 2022. Hazard ratios (HRs) and 95% CIs from multivariable Cox proportional hazards regression and multivariate nutrient-density models examined associations with mortality, adjusting for demographic, epidemiologic, and clinical factors. RESULTS:Among 4884 patients with nonmetastatic prostate cancer, the mean (SD) age at diagnosis was 69.5 (6.9) years. During follow-up, 3040 deaths from any cause were confirmed. When comparing patients in the highest quintile of saturated fat consumption with those in the lowest quintile, higher postdiagnostic saturated fat intake was associated with greater all-cause (HR, 1.24 [95% CI, 1.05-1.47), cardiovascular (HR, 1.42 [95% CI, 1.02-1.98]), and other cancer mortality (HR, 1.42 [95% CI, 0.93-2.17]). Animal fat, a major source of saturated fats, was also positively associated with all-cause mortality (HR, 1.14 [95% CI, 0.97-1.33]), as well as deaths from other cancers (HR, 1.49 [95% CI, 1.00-2.21]). Replacing 10% of calories from animal fats with plant-based fats (HR, 0.84 [95% CI, 0.76-0.93]) and replacing 5% of calories from saturated fats with monounsaturated fats (HR, 0.80 [95% CI, 0.70-0.91]) was associated with a decrease in all-cause mortality. There were no associations between dietary fats and prostate cancer mortality. CONCLUSIONS AND RELEVANCE:In this cohort study of patients with nonmetastatic prostate cancer, saturated fats, including animal fats, were associated with greater all-cause mortality owing to deaths from cardiovascular disease and other cancers. Diets rich in monounsaturated and polyunsaturated fats and plant-based fats after prostate cancer diagnosis were associated with improved survival outcomes for patients. These findings support evidence-based recommendations for patients and clinicians around dietary fat consumption to improve survivorship outcomes in the clinical setting of nonmetastatic prostate cancer.