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Double aortic arches are rare congenital malformations resulting from persistence of the right and left aortic arches, as opposed to normal regression of the left aortic arch. These vascular malformations can cause vascular rings since they encompass the trachea and esophagus, and lead to swallowing difficulties or respiratory difficulties from extrinsic compression. Typically, these are diagnosed in childhood but rarely may present in adults. In the presence of symptoms, which require formal gastrointestinal and pulmonary evaluation, surgical resection of the nondominant arch is typically recommended to release the vascular ring. Monitoring of the carotid and subclavian vasculature is performed intraoperatively to ensure distal perfusion is not affected following distal ligation of the arch.

Exposure of airway epithelia to environmental allergens or nanoparticles invokes a novel genome-protective physiological response to oxidative stress. Fragments of double-stranded genomic DNA released into the airway lumen originate from repetitive, transcriptionally active, and fragile sites within the genome. Exporting DNA with high repetitive content potentially aids cell survival through the preservation of genome integrity and fidelity during the repair process.

Importance Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. Objective To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). Design, Setting, and Participants This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. Exposures Tocilizumab or satralizumab. Main Outcomes and Measures Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. Results A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). Conclusions and Relevance In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.

Objective Vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome (VEXAS) syndrome is characterized by a complex spectrum of inflammatory and hematologic manifestations. Clinical research to identify effective therapies is urgently needed but is hindered by the lack of validated outcome measures. A VEXAS‐specific disease activity index (DAI) is an essential tool for reliably capturing changes in disease activity over time, thereby supporting clinical research and informing patient care in this emerging disease. This study aimed to develop a comprehensive DAI to assess disease‐related inflammation across affected organ systems in patients with VEXAS syndrome. Methods Inflammatory manifestations of VEXAS were previously identified through a systematic literature review and expert input. A multinational expert advisory committee developed the VEXAS‐DAI using modified Delphi methodology until consensus (defined as ≥75% concurrence) was reached. Item grading was adapted from the Common Terminology Criteria for Adverse Events. Scoring criteria were developed based on 158 test cases using the Physician Global Assessment of Inflammation. Results Consensus on the VEXAS‐DAI was achieved after four Delphi rounds. The index assesses inflammatory activity at the time of evaluation across 12 domains: inflammatory rash, chondritis, periorbital, ophthalmologic, joint, pulmonary, cardiovascular, genitourinary, neurologic, oral and gastrointestinal, renal, and constitutional symptoms. The total score ranges from 0 to 40. Conclusion The VEXAS‐DAI is a novel instrument designed to quantify active inflammation over time in patients with VEXAS. Prospective validation within a clinical trial setting is ongoing. image

ABSTRACT Background Shape‐sensing robotic‐assisted bronchoscopy (ssRAB) is a navigation platform for biopsy of indeterminate pulmonary lesions. Large‐scale, real‐world evidence confirming the safety profile of ssRAB compared to transthoracic needle biopsy (TTNB) is needed. Study Design and Methods A retrospective cohort study was performed using the PINC AI healthcare database among patients who underwent ssRAB or TTNB lung lesion biopsy at participating hospitals between April 2019 and March 2023. Outcomes were rates of pneumothorax and pneumothorax requiring chest‐tube intervention within 3 days, and rates of in‐hospital bleeding or all‐cause death. Quasi‐binomial logistic regression analysis was performed after one‐to‐five propensity score matching (PSM) accounting for patient‐ and hospital‐related characteristics. Results A total of 119 424 patients (5121 ssRAB, 114 303 TTNB) were identified with 4554 ssRAB and 14 319 TTNB patients after PSM. Relative to ssRAB, TTNB had significantly higher risk of pneumothorax (18.4% vs. 2.6%, OR = 7.10, p < 0.001) and pneumothorax requiring chest‐tube (10.8% vs. 1.4%, OR = 7.62, p < 0.001). TTNB was associated with a higher risk for bleeding (1.5% vs. 0.6%, OR = 2.20, p < 0.001) and all‐cause death (0.48% vs. 0.15%, OR = 2.47, p = 0.023); however, rates for both outcomes were relatively low. Interpretation In this large‐scale, real‐world database analysis with diverse patient populations, physician experience, and health care settings, ssRAB demonstrated a better safety profile compared to TTNB. Superior safety combined with a potentially comparable performance profile and known advantages of bronchoscopy, including concurrent staging, support ssRAB as an optimal choice for non‐surgical biopsies for suspicious pulmonary lesions.

Background. Chronic kidney disease (CKD) is a common complication of nonrenal transplantation, influencing recipients’ morbidity and mortality. The incidence of CKD varies depending on the transplanted organ. Recipients of vascularized composite allotransplantation (VCA) need lifelong immunosuppression similar to that of solid organ transplantation. This study investigated renal function in VCA recipients. Methods. We studied 70 recipients from 17 centers (median follow-up: 8 y): 59 upper extremity, 10 face, and 1 penis transplant. Pretransplant and posttransplant clinical data and sera were collected to calculate the estimated glomerular filtration rate (eGFR) using the CKD Epidemiology collaboration 2021 formula. Results. Pretransplantation, the median eGFR was 105.36 mL/min (range, 71.39–155.39 mL/min). By 3 mo posttransplant, the eGFR had significantly decreased to 78.42 mL/min (range, 32.49–130.74 mL/min; P = 0.001) before stabilizing. Despite higher tacrolimus levels at 3 mo, no correlation with eGFR was found. During follow-up, 17.1% of patients experienced a ≥50% eGFR decline, 10.9% progressed to CKD, and 4.7% developed end-stage kidney disease. Some risk factors were identified, but their responsibility could not be established with certainty because of the low number of severe renal outcomes. Conclusions. Renal function declines in the majority of VCA recipients, but the function loss is lower compared with nonrenal solid organ transplantation recipients. Although no statistically significant correlation could be established between tacrolimus exposure and renal function decline, strategies aiming at minimizing calcineurin inhibitor exposure and avoiding other nephrotoxic causes are recommended to preserve long-term kidney function.

Abstract Objective Genicular nerve radiofrequency (gRF) treatment is a widely used intervention for chronic pain from knee osteoarthritis (KOA). This systematic review and meta-analysis focuses on RCTs utilizing image guidance to address inconsistencies in previous reviews and provide higher-quality evidence. Design, Setting, and Methods This study included RCTs that compared gRF techniques (conventional, cooled, pulsed, bipolar) to non-gRF treatments, including sham procedures, intra-articular injections, ozone therapy, and oral medications. Primary and secondary outcomes were changes in pain and total WOMAC scores at 3, 6, and 12 months post-gRF treatments. Subgroup analyses explored differences by lesion size, use of prognostic blocks, industry sponsorship, and study location. Statistical heterogeneity was assessed via I 2 statistics. Results Eleven RCTs with 868 knee osteoarthritis patients (435 gRF, 433 non-gRF) were included. At 3 months, gRF significantly reduced pain (SMD -1.65, 95% CI: -3.20 to -0.10, I 2 = 98%, P = 0.040), but not at 6 months or 12 months. Secondary analyses showed no significant differences in total WOMAC scores between the gRF and control groups at 3, 6, and 12 months. Subgroup analysis showed that industry-sponsored studies reported significant 3-month pain reduction, whereas non-sponsored studies did not. This effect was independent of study location. Conclusions GRF provides short-term pain relief (up to 3 months) but neither functional improvement nor sustained pain reduction compared to non-gRF treatments. Our findings do not support the routine use of gRF for long-term chronic pain due to KOA.

Abstract Endocytosis regulates receptor trafficking and signaling, yet its role in colorectal cancer (CRC) remains unclear. We analyzed transcriptomic data from 15,025 CRC tumors to evaluate gene expression in clathrin-mediated endocytosis (CME) and the endosomal sorting complexes required for transport (ESCRT) pathway. Pathway-level signatures were compared across consensus molecular subtypes (CMS) and examined in relation to oncogenic signaling programs, while individual endocytosis-related genes were evaluated for associations with clinical outcomes in an independent randomized trial cohort. Expression of CME and ESCRT pathways varied by CMS, with the highest expression in CMS4 and the lowest in CMS3. Endocytosis signatures correlated with multiple oncogenic signaling pathways, including MAPK, TGF-β, WNT, PI3K, NOTCH, and angiogenesis, suggesting broad links between endocytic activity and tumor biology. In the randomized phase III CALGB/SWOG 80405 trial, low expression of AP2M1 —a core adaptor in the CME complex—was significantly associated with longer overall survival and progression-free survival in patients treated with anti-EGFR agents, but not in those receiving anti-VEGF agents. These findings suggest that endocytic trafficking may be associated with oncogenic signaling and differential therapeutic benefit in patients with metastatic CRC. The endocytosis pathway reflects biologically relevant heterogeneity in CRC and may help guide therapeutic stratification.

Abstract Background: Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerular disease characterized by glomerular fibrillar deposits and historically associated with poor kidney outcomes. Despite recent diagnostic advances, including DNAJB9 immunohistochemistry, the clinical spectrum, prognostic factors, and optimal management of FGN remain incompletely defined. Methods: We conducted a retrospective cohort study of patients with biopsy-proven FGN identified through the Cleveland Clinic Kidney Biopsy Epidemiology Project between January 2015 and March 2023. Results: Thirty patients met inclusion criteria. The cohort was predominantly female (70%) and white (86%), with a median age of 64 years. At the time of kidney biopsy, all patients had hypertension and acute or chronic kidney disease. Additional features included hematuria (76%), proteinuria (60%), and nephrotic syndrome (48%). Monoclonal protein was detected in 20% of cases. During a mean follow-up of 24 months (range 0–70 months; n = 13), 23% achieved partial remission, 23% had persistent disease, and 53% progressed to end-stage kidney disease (ESKD). Higher serum creatinine at biopsy was the only variable associated with progression to ESKD. Conclusion: FGN remains a rare glomerular disease with substantial risk of progression to kidney failure. This single-center cohort highlights the heterogeneous clinical presentation and generally poor kidney outcomes of FGN in the modern diagnostic era. Larger, multicenter studies are needed to refine prognostic stratification and guide evidence-based management strategies.

Study Design. Post hoc analysis of prospectively-collected data. Objective. To identify factors predicting the most (and least) satisfaction following surgery for cervical spondylotic myelopathy (CSM). Summary of Background Data. Patient satisfaction affects long-term outcomes after surgery but the preoperative factors that influence postoperative satisfaction have not been well studied in patients with CSM. Methods. We conducted a post hoc analysis of prospectively-collected data from the Quality Outcomes Database (QOD) CSM registry cohort. Baseline and surgical characteristics were compared for patients with CSM reporting the most [North American Spine Society Satisfaction Score (NASS) 1] and least (NASS 4) satisfaction 24 months postoperatively. A multivariable logistic regression model was constructed using backward stepwise elimination to determine significant predictors of most versus least satisfaction. Twenty-four-month patient-reported outcomes (PROs) were compared. Results. Overall, 1141 patients were prospectively enrolled with 948 (83.1%) reaching 24-month follow-up. Of these, 699 met prespecified inclusion criteria: 610 (87.3%) were most satisfied and 89 (12.7%) were least satisfied. Though there were mean improvements in all 24-month PROs for the most satisfied cohort ( P <0.001), there were no significant improvements in 24-month PROs for the least satisfied cohort ( P >0.05). Using multivariable logistic regression modeling, a preoperative symptom of upper extremity weakness (OR=2.5, P =0.003), subjective myelopathy (OR=2.0, P =0.04), absence of numbness complaints (OR=2.2, P =0.003), symptom duration under 12 months (OR=1.6, P =0.047), Caucasian race (OR=2.3, P =0.001), participation in activities outside of the home (OR=2.0, P =0.04), anterior approach (OR=2.3, P <0.001), and higher baseline quality of life (OR=4.0, P =0.01) were predictive of the most satisfaction. Conclusion. Compared with the least satisfied, those most satisfied following surgery for CSM more often had a preoperative symptom of arm weakness, subjective myelopathy, the absence of numbness complaints, symptom duration under 12 months, higher baseline quality of life, and participation in activities outside of the home. Compared with a posterior approach, an anterior approach was associated with the most satisfaction. Taken together, early surgical treatment--before myelopathic symptoms significantly impact one's quality of life--may be considered to optimize patient satisfaction following CSM surgery.