Faculty Bibliography

IMPORTANCE/UNASSIGNED:Lower estimated glomerular filtration rate (eGFR) is associated with increased rates of death and kidney and cardiovascular events. Associations of measured GFR (mGFR) with outcomes remain unclear. OBJECTIVE/UNASSIGNED:To quantify associations between mGFR and adverse clinical outcomes and to compare these with eGFR-based associations. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Retrospective observational cohort study of 6174 adults from Stockholm, Sweden, between January 1, 2011, and December 31, 2021. EXPOSURE/UNASSIGNED:Measured GFR was obtained based on plasma clearance of intravenously administered iohexol (primary independent variable of interest). Estimated GFR was calculated with plasma creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys), using the Chronic Kidney Disease Epidemiology Collaboration 2021 and 2012 equations. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were all-cause mortality and kidney failure with replacement therapy. Associations of each GFR measure with outcomes were evaluated using hazard ratios adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), medical history, medications, and urine albumin to creatinine ratio. RESULTS/UNASSIGNED:Of 6174 participants (median age, 59 years [IQR, 43-69]; 3686 [60%] were male and 2488 [40%] were female), 1977 (32%) died and 426 (6.9%) developed kidney failure with replacement therapy during a median follow-up of 5.9 years (IQR, 3.0-8.8 years). Compared with a baseline mGFR of 90 mL/min/1.73 m2, an mGFR of 60 mL/min/1.73 m2 was associated with higher rates of all-cause mortality (27.6 vs 22.4 per 1000 person-years; hazard ratio [HR], 1.21; 95% CI, 1.14-1.28) and kidney failure with replacement therapy (1.2 vs 0.4 per 1000 person-years; HR, 2.85; 95% CI, 2.06-3.94). For all-cause mortality, associations for eGFRcr-cys did not significantly differ from those for mGFR (ratio of HRs [RHRs] at 60 mL/min/1.73 m2, 1.03; 95% CI, 0.96-1.10), whereas eGFRcr underestimated the mGFR-based association (RHR, 0.87; 95% CI, 0.79-0.95) and eGFRcys overestimated it (RHR, 1.17; 95% CI, 1.08-1.27). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Among adults in Sweden, mGFR values of 60 mL/min/1.73 m2 were associated with higher rates of all-cause mortality and kidney failure compared with mGFR values of 90 mL/min/1.73 m2, supporting the current GFR threshold of 60 mL/min/1.73 m2 to define chronic kidney disease. Associations of mGFR with mortality were most closely represented by the association of eGFRcr-cys with mortality, whereas eGFRcr underestimated and eGFRcys overestimated mortality risk.

IMPORTANCE/UNASSIGNED:Neighborhood segregation, a mechanism of structural racism, is associated with racial and ethnic disparities in health care access and outcomes. Live donor liver transplant (LDLT) is the ideal treatment for cirrhosis, improving survival and quality of life. Understanding the role of segregation in LDLT access is important to address disparities. OBJECTIVE/UNASSIGNED:To assess the associations between residential and transplant center neighborhood segregation and LDLT access. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from a US national transplant registry on adult candidates (age ≥18 years) for first-time liver transplant between February 1, 2016, and June 30, 2025, at centers that performed 1 or more LDLT annually during that time. EXPOSURE/UNASSIGNED:Residential and transplant center neighborhood segregation, measured using the Thiel H method at the zip code tabulation area level and dichotomized at the respective median values. MAIN OUTCOMES AND MEASURES/UNASSIGNED:A Cox proportional hazards regression model quantified the adjusted hazard ratio (AHR) of LDLT and included interactions with race and ethnicity and insurance. LDLT access within high-segregation residential neighborhoods by racial and ethnic composition (predominantly White or predominantly racial and ethnic minoritized population) was also quantified. RESULTS/UNASSIGNED:Among 22 223 adult liver transplant candidates, mean (SD) age was 55.3 (11.2) years, 13 518 (60.8%) were male, 1476 (6.6%) were Black, 5097 (22.9%) were Hispanic or Latino, and 15 650 (70.4%) were White. Most (11 669 [52.5%]) had private insurance. After adjustment, candidates residing in high-segregation neighborhoods had lower likelihood of LDLT access (AHR, 0.81; 95% CI, 0.74-0.88). Hispanic or Latino candidates in high-segregation neighborhoods had lower likelihood of LDLT access than their counterparts in low-segregation neighborhoods (AHR, 0.59; 95% CI, 0.49-0.72; P < .001 for interaction), but associations between neighborhood segregation and LDLT did not vary significantly by insurance type (P = .52 for interaction). Candidates wait-listed at transplant centers in high-segregation neighborhoods had lower likelihood of LDLT access (AHR, 0.64; 95% CI, 0.59-0.70). Candidates with Medicare or Medicaid wait-listed at centers in high-segregation neighborhoods had lower likelihood of LDLT access than their counterparts in low-segregation neighborhoods (AHR, 0.53; 95% CI, 0.45-0.51; P < .001 for interaction). Within high-segregation residential neighborhoods, candidates in neighborhoods with a larger racial and ethnic population had lower likelihood of LDLT access than those living in neighborhoods with a larger White population (AHR, 0.68; 95% CI, 0.59-0.78). CONCLUSION AND RELEVANCE/UNASSIGNED:In this national cohort study, living in or being wait-listed at centers in high-segregation neighborhoods was associated with lower likelihood of LDLT access and candidates living in high-segregation neighborhoods with a larger racial and ethnic minority population compared with a larger White population had lower likelihood of LDLT. Investing in high-segregation neighborhoods to address these structural disadvantages may help improve equity in LDLT access.

OBJECTIVE:To report 7-year oncological outcomes of focal cryo-ablation (FCA) for focal intermediate favorable risk prostate cancer (IFRPCa). PATIENTS AND METHODS/METHODS:Beginning March 2017, all men with focal IFRPCa undergoing FCA meeting the following eligibility criteria were enrolled in our longitudinal prospective study: a single MRI PIRADS 2-5 target concordant with unilateral IFRPCa, no gross extra-prostatic extension or very distal apical disease on MRI, and no Grade Group (GG) ≥2 contralateral to the MRI target. The oncological surveillance protocol included PSA testing every 6 months, and MRI testing at 6-12 months, 2, 3.5, 5.0, and 7.5 years. Prostate biopsy was performed for rising PSA, suspicious MRI's or at the discretion of the surgeons. The main outcome measure was clinically significant prostate cancer (csPCa) recurrence. RESULTS:276 men were enrolled in the study. Overall, 39 (14.1%) developed a csPCa recurrence. Baseline mean PSA was significantly greater in subjects developing csPCa recurrence. There were no prostate cancer mortalities and 3 (0.01%) developed metastasis. The csPCa recurrence free survival at 3, 5 and 7 years was 90.20%, 78.36%, and 70.31%, respectively. African American race was the only significant independent predictor for developing a csPCa recurrence. Compliance with protocol MRI at 7.5 years was 90.9%. CONCLUSIONS:The present study supports FCA as a treatment option for focal IFRPCa associated with an MRI target with no evidence of extra-capsular extension or distal apical disease on MRI, and no contralateral GG> 1 disease.

INTRODUCTION/BACKGROUND:The purpose of this study was to determine whether CT Hounsfield units (HUs) as a proxy for bone quality can predict postoperative mechanical complications following surgical treatment of distal humerus fractures. METHODS:One hundred fifty-three patients with both column distal humerus fractures who underwent surgical fixation at single institution and had complete radiographic data available were included. Radiographic measurements included the HU value from the surgical distal humerus as determined by measuring the metaphyseal/supracondylar at the midaxial/coronal/sagittal CT image an average of 1 cm from the articular surface using a freehand region of interest. Zones with fracture lines and cortical impaction were avoided for all measurements. Postoperative complications recorded were implant failure, nonunion, and acute periprosthetic fracture. Patients with and without complications were statistically compared, and binary logistic regression was done to determine if CT HU measurements from the distal humerus were predictive of complications. RESULTS:Five patients (3.3%) developed five mechanical complications, including peri-prosthetic humerus fracture (one), implant failure (two), and nonunion (two). Patients with mechanical complications were more likely to be current smokers (40% vs. 6.8%, P = 0.010). Otherwise, no difference was observed in demographics or AO/Orthopedic Trauma Association classification between the cohorts. Patients with complications had markedly lower HU in the coronal plane (P = 0.031). Regression analysis found that current smoking was associated with an increased risk of mechanical complications (P = 0.041, OR = 1.102, 95% confidence interval [CI], 1.087 to 1.710), whereas a higher coronal HU was associated with a decreased risk of complications (P = 0.048, OR = 0.973, 95% CI, 0.961 to 0.991). CONCLUSION/CONCLUSIONS:A thorough smoking history and CT HU measurements in the coronal plane may identify patients with poorer bone quality at higher risk for postoperative mechanical complications following distal humerus fracture fixation.

Along with irreparable labrum from failed prior surgery, diminutive or calcified labrum in cases of primary surgery have become an indication for labral reconstruction of the hip. Radiologists can reliably and accurately measure the labral width or height and volume on magnetic resonance imaging (MRI). For preoperative purposes, an MRI that confirms a diminutive labrum can lead the surgeon to indicate primary labral reconstruction as the native labrum may not be providing an adequate suction seal to the femoral head. For postoperative purposes, MRI measurements of the volume of the labral graft can provide the surgeon and patient with important information about the healing progress and ultimate success of the reconstruction. Future routine postoperative MRI measurements of labral volume will help the hip arthroscopist determine the ideal volume of the labral reconstruction graft.

Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase 2b KEYNOTE-942 study (NCT03897881). Eligible patients with resected stage IIIB‒IV cutaneous melanoma were randomized 2:1 to receive 9 doses of intramuscular intismeran 1 mg Q3W plus 18 doses of intravenous pembrolizumab 200 mg Q3W or 18 doses of intravenous pembrolizumab 200 mg Q3W. Primary endpoint was recurrence-free survival (RFS); secondary endpoints included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomized patients (intismeran plus pembrolizumab, n=107; pembrolizumab, n=50), median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5‒76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (HR, 0.510; 95% CI, 0.294‒0.887) and DMFS (0.411; 0.200‒0.843), with a favorable trend in overall survival (0.471; 0.165‒1.345) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After 5 years' follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.

BACKGROUND:Facial trauma surgeons consulted by emergency departments (EDs) for mandible fractures must decide whether hospital admission is warranted. While admission may allow for closer monitoring and expedited surgery, many patients present with clinically stable injuries for which outpatient management is feasible. PURPOSE/OBJECTIVE:This study aims to identify biological, situational, and socioeconomic predictors of admission for mandible fractures presenting to EDs across the United States. STUDY DESIGN, SETTING, AND SAMPLE/UNASSIGNED:This was a retrospective cohort study of the 2022 Nationwide Emergency Department Sample. Subjects diagnosed with mandible fractures (International Classification of Diseases, 10th Revision, Clinical Modification S02.6-) were included. Subjects who died in the ED or left against medical advice were excluded. PREDICTOR VARIABLES/METHODS:The predictor variables consisted of a heterogeneous set of demographic, hospital-related, and injury-related risk factors. MAIN OUTCOME VARIABLES/METHODS:The outcome variables were admission status and ED charges. COVARIATES/UNASSIGNED:None. ANALYSES/METHODS:tests. A multivariable logistic model was used to identify independent predictors of admission. A P value <.05 was considered statistically significant. RESULTS:The sample was composed of 12,160 subjects with a mean age of 39 years (SD = 19), and 9,117 (75%) were male. A total of 5,236 (43%) subjects were admitted. Mandibular symphysis fractures had the highest likelihood of admission (P < .001), whereas body fractures had the lowest likelihood (P < .001). In a multivariable logistic model, male sex (OR: 1.23; 95% CI: 1.11 to 1.36), number of mandible fractures (OR: 2.81; 95% CI: 2.61 to 3.02), concomitant midface fractures (OR: 3.25; 95% CI: 2.89 to 3.65), and firearm injuries (OR: 16.16; 95% CI: 11.50 to 22.71) were associated with admission, whereas uninsured patients were less likely to be admitted (OR: 0.84; 95% CI: 0.75 to 0.94). Admissions were more costly than discharges ($15,511 vs $4,899, P < .001). CONCLUSION AND RELEVANCE/CONCLUSIONS:Disposition decisions for mandible fractures are influenced by not only injury severity (eg, multiple mandible fractures, concomitant facial fractures) but also patient characteristics and socioeconomic factors. These findings support the development of standardized admission criteria to improve equity and resource utilization.

The protein activating molecule in Beclin1-regulated autophagy1 (AMBRA1), discovered in 2007, is crucial for autophagy and plays roles in nervous system development, cell survival, and proliferation. Here, we investigated AMBRA1's involvement in various cellular processes using a systems-based "omics" approach, focusing on melanoma. Transcriptomic analysis of AMBRA1 overexpression or knock-down was shown to result in significant dysregulation of several transcripts. We identified several novel roles for AMBRA1 in a range of cellular pathways including cancer signaling pathways such as MAPK, angiogenesis, tissue growth factor signaling, axon guidance, and Wnt signaling. Furthermore, using yeast two-hybrid assays, we identified novel binding partners which provide evidence of new roles for AMBRA1 in different cellular processes. Ultimately, we conclude that AMBRA1 loss upregulates metastatic genes/proteins highlighting AMBRA1 as a tumor suppressor gene in melanoma.

Mindfulness meditation has received growing interest in research over the past decades. Mindfulness meditation training (MMT) can be employed as a mental practice to improve cognitive skills such as attention and emotion regulation and may promote well-being. Neuroimaging studies have emerged to understand the effects of MMT on brain functioning. However, no review exists on the effects of MMT on resting-state brain functional connectivity (rsFC) in healthy meditation-naïve adults specifically. We, therefore, aimed to provide an overview of studies that investigated the effects of MMT on rsFC in healthy meditation-naïve adults, as well as their link to cognitive and clinical measures. Several studies reported changes in MMT-induced rsFC within and between regions of the default mode (DMN), salience (SN), and central executive (CEN) networks. Both increases and decreases in rsFC have been observed for brain regions associated with these networks after MMT, each with differential roles in emotion regulation, stress, and cognitive functions. Some studies highlighted associations between changes in rsFC after MMT and modifications in cognitive performance and psycho-affective measures, which may be influenced by MMT-specific characteristics such as practice duration or delivery methods. MMT may induce a reorganization in the brain's functional architecture by altering rsFC within and between these networks and seems to modify processes related to attention, executive memory, emotional regulation, stress, and resilience. Investigating functional connectivity during rest in key brain networks seems a promising approach to understand the effects of mindfulness meditation on overall well-being.