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Abstract Rationale This Registry was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to arrest the rate of FEV1 decline (FEV1 decline) and prolong survival in lung allograft recipients with Bronchiolitis Obliterans refractory to standard of care therapy. Methods After IRB approval, 258 lung transplant recipients were enrolled from 20 US lung transplant centers. Subjects were assigned to ECP treatment (ECPRx) (i.e., 24 procedures over 6 months) at or a few months after enrollment based on spirometric criteria. Maintenance ECPRx (mECP) was at the discretion of managing clinicians. Rate of FEV1 decline in mL/month (FEV1 decline) was compared between 6 months prior to and 6 & 12 months after ECPRx initiation using linear mixed effects models. Time 0 for survival was set as the start of ECPRx for generation of Kaplan-Meier curves. Hazard Ratios (HR) with 95% confidence intervals (lower-upper) were generated using Cox Proportional Hazards Regression to characterize significant (p < 0.05) independent associations of mECP and/or any other covariates (i.e., demographic, operative, enrollment site, spirometric ) and survival. Results An 89% (78%-96%) decrease in the FEV1 decline was observed 12 months after ECPRx initiation in 191 participants assigned to ECPRx. FEV1 decline (-164 mL/month: 144-185) was greater (p < 0.001) in participants who expired within six months of Time 0 (n = 28) vs participants (-111 mL/month: 101-120) who died six months after Time 0 (n = 77). Of 159 participants who survived for at least six months after ECPRx initiation, 40 participants without mECP, who had up to 24 ECPRx (ECPRx: n = 19), had a lower survival HR: 2.43(1.75-3.4) (p < 0.001) relative to 119 participants who received mECP (ECPRx: n = 86)(see Figure). The response to ECPRx (% Change in FEV1 decline prior to and 6 months after 1st ECP) was similar between subcohorts (No mECP: -81 decrease vs mECP: -85%, p = 0.3). The association of mECP persisted after multivariate adjustment HR 1.8 (1.8-2.7)(p = 0.002) using significant covariates: FEV1 HR 0.37 (0.3-0.5), FEV1 decline HR 0.001 (0.001-0.04), Male Gender HR 2.4 (1.7-3.4); Reflux Disease HR 1.8 (1.2-2.8); Coronary Disease HR 1.8 (1.2-2.7). Conclusions This analysis indicates that mECP is independently associated with enhanced survival most likely due to attenuation of relapse six months after ECP initiation based on similar initial response to ECPRx. A risk-adjusted, control cohort is being pursued to facilitate submission of a scientifically rigorous petition to CMS to expand the ECP National Coverage Decision to include BOS predicated on CMS 2024 scientific guidelines. This abstract is funded by: Therakos Inc

Background: Rotator cuff tears are a common orthopaedic injury often resulting in shoulder pain and functional impairment. Despite the prevalence of rotator cuff tears, the incidence of retear after rotator cuff repair (RCR) remains high. There is growing interest in the use of structural augmentation in RCR to decrease retear rates and improve patient outcomes. Purpose: The purpose of this systematic review and meta-analysis was to compare the clinical and imaging outcomes of structural augmentation versus standard RCR in patients with full-thickness rotator cuff tears. The effectiveness of different augment subtypes was also assessed. Study Design: Meta-analysis; Level of evidence, 3. Methods: A comprehensive literature search was conducted in CENTRAL, Embase, and Medline from inception to November 13, 2024. Eligible studies included comparative trials evaluating structural augmentation in RCR for repairable full-thickness tears. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized controlled trials and the MINORS (Methodological Index for Non-randomized Studies) score for observational studies. Meta-analyses were performed via a random effects model, with subgroup analyses performed by study design and augment type. Results: Twenty-four studies (12 randomized controlled trials and 12 cohort studies) were included in this review, all of which evaluated biologic augments (xenograft, allograft, autograft). Structural augmentation significantly reduced the risk of retear by 35% as compared with standard RCR (risk ratio, 0.65; 95% CI, 0.48-0.89; P = .01). Retears were confirmed radiographically by magnetic resonance imaging or ultrasound. Subgroup analysis revealed the greatest reduction in retear rates with allograft augmentation (risk ratio, 0.34; 95% CI, 0.21-0.56). No significant differences were observed in patient-reported outcomes, including pain scores, American Shoulder and Elbow Surgeons scores, or Constant scores. Conclusion: Structural augmentation in RCR significantly reduces retear rates, particularly with allografts, but does not improve short-term patient-reported outcomes. Further research is needed to identify which patient and tear characteristics may influence the effectiveness of augmentation.

Background. The spirometric response to standard-of-care (SOC) immunosuppressive therapy for the management of bronchiolitis obliterans syndrome (BOS) has been sparsely reported in the literature. Data from a Medicare-approved Registry were analyzed to characterize the effectiveness/durability of a wide range of SOC interventions to manage the decline of lung function and to validate the study spirometric criteria for initiation of rescue therapy. Methods. Lung transplant recipients with refractory BOS at 21 US collaborating centers were enrolled in the Registry. Data included both nonspirometric (eg, demographic, Immunosuppressive Regimens for management of BOS) and spirometric parameters (ie, forced expiratory volume in 1 s [FEV 1 ] measurements and derived indices). The utility of study FEV 1 criteria for treatment (ie, statistically significant rate of FEV 1 decline >30 mL/mo) was evaluated by comparing the spirometric course between participants who met or did not meet this criterion. Results. Only 21% of participants treated with SOC therapy had >50% decrease (76 ± 25% decrease) in the rate of FEV 1 decline. Although 51% of participants had a partial response (rate of FEV 1 decline decreased on average 71%), 49% of participants had a substantial increase (mean increase 224%). The FEV 1 criterion for treatment was able to identify 19% of participants (48/258) who achieved durable stabilization (ie, nonsignificant rate of FEV 1 <30 mL/mo) with SOC therapy. Conclusions. Patients with BOS have a widely variable response to SOC therapy. Our findings support the use of FEV 1 rate of decline to assess response to SOC therapy and to ensure appropriate assignment of participants with refractory BOS to rescue therapy treatment cohorts.

BACKGROUND. We developed a prospective, multicenter “registry” to evaluate the effect of extracorporeal photopheresis for lung transplant recipients who develop chronic lung allograft dysfunction (CLAD) with the bronchiolitis obliterans syndrome (BOS) phenotype (CLAD/BOS) and who are refractory to conventional standard-of-care therapy. METHODS. Data from 258 lung transplant recipients enrolled in the Registry between April 2015 and April 2022 were included in this analysis. All recorded parameters (eg, demographics), including forced expiratory volume in 1 s (FEV1) measurements and indices (FEV1% baseline, FEV1 rate of decline) at several time periods, were included in multivariate linear/logistic and Kaplan-Meier analyses to evaluate potential associations with survival. RESULTS. Mortality at 6 and 12 mo after CLAD/BOS diagnosis was 5% and 14%, whereas mortality at 6 and 12 mo after enrollment was 15% and 26%, respectively. The primary cause of death in the cohort was respiratory failure or graft failure (74%). Rate of FEV1 decline (log) at enrollment was independently associated with survival (log days) from CLAD/BOS diagnosis and enrollment (r = 0.55 and r = 0.3, respectively). The rates of FEV1 decline among survivors were lower (–77 ± 89 mL/mo) compared with nonsurvivors (–148 ± 155 mL/mo) at 6 mo after enrollment (P = 0.0001). CONCLUSIONS. The rate of FEV1 decline quantified using at least 5 FEV1 measurements is a robust surrogate outcome. We plan to use these findings to revise our randomized controlled trial to facilitate risk adjustment using FEV1 rate of decline strata at enrollment and as a scientifically valid surrogate for outcome.

SummaryBackgroundThere is limited real‐world data on comparative effectiveness of different biologic or small molecule agents as second‐line therapies in patients with ulcerative colitis (UC) with prior exposure to a tumour necrosis factor inhibitor (TNFi).MethodsWe conducted a retrospective cohort study using TriNetX, a multi‐institutional database to assess the efficacy of tofacitinib, vedolizumab and ustekinumab in patients with ulcerative colitis (UC) with prior exposure to a TNFi. Failure of medical therapy was defined as a composite outcome of intravenous steroids or colectomy within 2 years. One‐to‐one propensity score matching was performed for demographics, disease extent, mean haemoglobin, C‐reactive protein, albumin and calprotectin, prior IBD medications and steroid use between cohorts.ResultsAmong 2141 patients with UC and prior exposure to TNFi, 348 (16.2%), 716 (33.4%) and 1077 (50.3%) were switched to tofacitinib, ustekinumab and vedolizumab, respectively. After propensity‐score matching, there was no difference in the composite outcome (aOR: 0.77, 95% CI: 0.55–1.07) but higher risk of colectomy (aOR: 2.69, 95% CI: 1.31–5.50) in the tofacitinib cohort than the vedolizumab cohort. There was no difference in the risk of composite outcome (aOR: 1.29, 95% CI: 0.89–1.86) but higher risk of colectomy (aOR: 2.63, 95% CI: 1.24–5.58) in the tofacitinib cohort than the ustekinumab cohort. The vedolizumab cohort had a higher risk of composite outcome (aOR: 1.67, 95% CI: 1.29–2.16) than the ustekinumab cohort.ConclusionUstekinumab might be the preferred second‐line therapy over tofacitinib and vedolizumab in patients with UC that were previously exposed to a TNFi.

Abstract Introduction Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes. Methods We conducted a multicenter retrospective analysis of shared quality data points for the endoscopic endonasal approach (EEA) for pituitary adenomas, along with other sellar and parasellar region masses that were included by participating institutions. Patient and operative characteristics, perioperative and postoperative antibiotic regimens and their durations, intraoperative and postoperative cerebrospinal fluid leak, and onset of postoperative meningitis and sinusitis were compared. Results Fifteen institutions participated and provided 6 consecutive months' worth of case data. Five hundred ninety-three cases were included in the study, of which 564 were pituitary adenomectomies. The incidences of postoperative meningitis and sinusitis were low (0.67 and 2.87% for all pathologies, respectively; 0.35% meningitis for pituitary adenomas) and did not correlate with any specific antibiotic regimen. Immunocompromised status posed an increased odds of meningitis in pituitary adenomectomies (28.6, 95% confidence interval [1.72–474.4]). Conclusions The results show no clear benefit to postoperative antimicrobial use in EEA, with further larger studies needed.

SummaryBackgroundAn association between bariatric surgery and development of de‐novo inflammatory bowel disease (IBD) has been observed.AimTo evaluate further the association among bariatric surgery, weight loss medications, obesity and new‐onset IBD.MethodsUsing Explorys, a population‐based Health Insurance Portability and Accountability Act compliant database, we estimated the prevalence of de‐novo IBD among patients treated with bariatric surgery (Roux‐en‐Y gastrojejunostomy, laparoscopic sleeve gastrectomy or gastric banding) (n = 60 870) or weight loss medications (orlistat, phentermine/topiramate, lorcaserin, bupropion/naltrexone and liraglutide) (n = 193 790) compared with obese controls (n = 5 021 210), between 1999 and 2018.ResultsThe prevalence of de‐novo IBD was lower among obese patients exposed to bariatric surgery (7.72 per 1000 patients) or weight loss medications (7.22 per 1000 patients) compared with patients with persistent obesity not exposed to these interventions (11.66 per 1000 patients, P < 0.0001). The risk reduction for de‐novo IBD was consistent across bariatric surgeries and weight loss medications with the exception of orlistat which was not associated with a reduction in risk for de‐novo IBD compared with the persistent obese control cohort.ConclusionObese patients undergoing treatment with bariatric surgery or weight loss medications are at a lower risk for developing de‐novo IBD compared with persistently obese controls not exposed to these interventions. These data suggest that obesity and ineffective management of obesity are risk factors for de‐novo IBD. Further research is needed to confirm these observations and understand potential mechanisms.

Disseminated infection with Ureaplasma species causes fatal hyperammonemia syndrome in lung transplant recipients, likely by disrupting ammonia metabolism.