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ImportanceThe safety and effectiveness of combining surgical peripheral iridectomy (SPI) with goniosynechialysis (GSL) and goniotomy (GT) vs trabeculectomy for intraocular pressure (IOP) reduction remains unknown.ObjectiveTo investigate the safety and effectiveness at 1 year of SPI + GSL + GT vs trabeculectomy in advanced primary angle-closure glaucoma (PACG) without cataract.Design, Setting, and ParticipantsThis noninferiority randomized clinical trial was conducted at 8 tertiary eye centers in China. A total of 88 Chinese patients (88 eyes) with advanced PACG without cataract were enrolled from January 2022 to July 2023. Data were analyzed from August 2024 to September 2024. Mean (SD) patient age was 60.3 (7.3) years, and 52 patients (59.1%) were female. Forty-three patients were randomized to SPI + GSL + GT and 45 were randomized to trabeculectomy; 86 patients (97.7%) completed the 12-month follow-up.InterventionsParticipants were randomized 1:1 to receive SPI + GSL + GT or trabeculectomy.Main Outcomes and MeasuresThe primary outcome was IOP at 12 months (noninferior margin: 4 mm Hg). Secondary outcomes included surgical success (IOP: 5-18 mm Hg, ≥20% reduction from baseline, with or without antiglaucoma medications); postoperative complications and interventions, including bleb massage, suture lysis, or releasable sutures; and number of antiglaucomatous medications prescribed.ResultsAt 12 months, the SPI + GSL + GT group had a mean (SD) IOP of 15.6 (4.0) mm Hg vs 14.9 (4.2) mm Hg in the trabeculectomy group (difference, 0.5 mm Hg; 95% CI, −1.2 to 2.2; P = .55), which was within the 4-mm Hg noninferiority margin. Qualified success rates were 38 of 43 participants (88.4%) for SPI + GSL + GT and 42 of 45 participants (93.3%) for trabeculectomy (difference, −5.0%; 95% CI, −19.6% to 8.5%; P = .48). However, complete success rates were lower in the SPI + GSL + GT group (26 participants [60.5%]) vs the trabeculectomy group (37 participants [82.2%]; difference, −21.8%; 95% CI, −40.2% to −2.4%; P = .03). Postoperative complications were present for 8 participants (18.6%) in the SPI + GSL + GT group vs 9 participants (20.0%) in the trabeculectomy group (difference, −1.4%; 95% CI, −17.9% to 15.1%; P = .71). Postoperative interventions were lower in the SPI + GSL + GT group (3 participants [7.0%] vs 25 participants [55.6%]; difference, 48.6%; 95% CI, 32.2%-65.0%; P < .001). Median (IQR) numbers of medications used decreased from 2 (0-3) to 0 (0-1) in the SPI + GSL + GT group and from 2 (2-3) to 0 (0-0) in the trabeculectomy group (difference, −0.81; 95% CI, −1.36 to −0.26; P = .004).Conclusions and RelevanceIn this randomized clinical trial among patients with advanced PACG without cataract, SPI + GSL + GT demonstrated noninferiority (4-mm Hg margin) to trabeculectomy for IOP at 12 months, with fewer interventions (including bleb massage, suture lysis, or releasable sutures) but no difference in postoperative medication use. This suggests SPI + GSL + GT as a potential alternative to trabeculectomy for similar cases, pending validation in larger sample sizes with smaller noninferiority margins.Trial RegistrationClinicalTrials.gov Identifier: NCT05163951

ImportanceIntraocular pressure (IOP) reduction with phacogoniotomy (phacoemulsification plus goniosynechialysis plus goniotomy) was not less than that of phacotrabeculectomy for advanced primary angle-closure glaucoma (PACG) with cataract at 1-year follow-up, but longer-term outcomes are needed.ObjectiveTo investigate if phacogoniotomy is noninferior to phacotrabeculectomy for advanced PACG with cataract at 2 years.Design, Setting, and ParticipantsThis multicenter, noninferiority, randomized clinical trial took place in 7 ophthalmology centers in China. The trial started May 31, 2021, and 2-year follow-up ended May 31, 2024. Included in this analysis were patients with advanced PACG and cataract. Study data were analyzed from September 2024 to January 2025.InterventionsRandom assignment (1:1) to phacogoniotomy or phacotrabeculectomy.Main Outcomes and MeasuresThe primary outcome measure was reduction in IOP from baseline to the 2-year visit with a noninferiority margin of 4 mm Hg.ResultsA total of 124 participants (124 eyes) were randomized (mean [SD] age, 66.4 [8.6] years; 67 female [54.0%]), 65 (52.4%) to the phacogoniotomy group and 59 (47.6%) to the phacotrabeculectomy group. A total of 59 patients (90.7%) in the phacogoniotomy group and 52 patients (88.1%) in the phacotrabeculectomy group completed 2-year visits. All participants were Chinese. Mean (SD) IOP reduction was −25.6 (10.2) mm Hg and −24.7 (9.4) mm Hg in the phacogoniotomy and phacotrabeculectomy groups, respectively, and the upper boundary of the CI for difference in change between groups was lower than the 4-mm Hg noninferiority margin (mean difference, −0.5 mm Hg; 97.5% CI, −1.7 mm Hg to 0.8 mm Hg; P = .42). The mean difference for complete success for phacogoniotomy vs phacotrabeculectomy was −6.7% (95% CI, −21.4% to 8.8%; P = .47) and for qualified success was 1.4% (95% CI, −11.0% to 14.3%, P = .30). Median (IQR) number of antiglaucomatous medication was 0 (0) vs 0 (0; Hodges-Lehmann estimate of location shift, 0; 95% CI, 0; P =.12) with phacogoniotomy vs phacotrabeculectomy, respectively (mean difference, 0.13; 95% CI, −0.36 to 0.63; P = .60).Conclusions and RelevanceMean IOP reduction with phacogoniotomy was noninferior to phacotrabeculectomy for advanced PACG and cataract at 2-year follow-up with no differences detected in complete or qualified success or mean number of antiglaucomatous medications. These findings support phacogoniotomy as an alternative to phacotrabeculectomy for patients with advanced PACG and cataract.Trial registrationClinicalTrials.gov Identifier: NCT04878458

PURPOSE Long-term androgen deprivation therapy (ADT) improves survival in men with high-risk localized prostate cancer (PCa) receiving radiotherapy (RT). Predictive biomarkers are needed to guide ADT duration. METHODS A multimodal artificial intelligence (MMAI)–derived predictive biomarker was trained for long-term (LT) versus short-term (ST) ADT using pretreatment digital prostate biopsy images and clinical data (age, prostate-specific antigen, Gleason, and T stage) from six NRG Oncology phase III randomized radiotherapy trials. The novel MMAI-derived biomarker was developed to predict the differential benefit of LT-ADT on the primary end point, distant metastasis (DM). MMAI predictive utility was validated on a seventh randomized trial, RTOG 9202 (N = 1,192), which randomly assigned men to RT + ST-ADT (4 months) versus RT + LT-ADT (28 months). Fine-Gray and cumulative incidence analyses for DM, and secondarily, death with DM, were performed. Deaths without DM were treated as competing risks. RESULTS In the validation cohort (median follow-up, 17.2 years), LT-ADT significantly improved DM from 26% to 17% (subdistribution hazard ratio [sHR], 0.64 [95% CI, 0.50 to 0.82], P < .001). A significant biomarker-treatment predictive interaction was observed ( P = .04) for DM, whereby MMAI biomarker–positive men (n = 785, 66%) had reduced DM with LT-ADT versus ST-ADT (sHR, 0.55 [95% CI, 0.41 to 0.73], P < .001), whereas no treatment benefit was observed for MMAI biomarker–negative men (n = 407; sHR, 1.06 [95% CI, 0.61 to 1.84], P = .84). The estimated 15-year DM risk difference between RT + LT-ADT and RT + ST-ADT was 14% in MMAI biomarker–positive men and 0% in MMAI biomarker–negative men. The MMAI biomarker was also prognostic for DM, irrespective of treatment (sHR, 2.35 [95% CI, 1.72 to 3.19], P < .001). CONCLUSION To our knowledge, the MMAI model is the first validated predictive biomarker to guide ADT duration with RT in localized/locally advanced PCa. Approximately one third of men with high-risk PCa could safely be spared the additional 24 months of ADT and the associated morbidity.

Abstract Rationale Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. Objectives To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. Methods Prepandemic obstruction (FEV1/FVC &lt; 0.70) and restriction (FEV1/FVC ⩾ 0.7, FVC &lt; 80%) were defined based on the most recent spirometry exam conducted in 11 prospective U.S. general population–based cohorts. Severe obstruction was classified by FEV1 &lt; 50%. Percentage emphysema, percentage high-attenuation areas, and interstitial lung abnormalities were defined on computed tomography in a subset. Incident COVID-19 was ascertained via questionnaires, serosurvey, and medical records from 2020 to 2023 and classified as severe (hospitalized or fatal) or nonsevere. Cause-specific hazard models were adjusted for sociodemographics, anthropometry, smoking, comorbidities, and COVID-19 vaccination status. Measurements and Main Results Among 29,323 participants (mean age, 67 yr), there were 748 severe incident COVID-19 cases over median follow-up of 17.3 months from March 1, 2020. Greater hazards of severe COVID-19 were associated with severe obstruction (vs. normal; adjusted hazard ratio [aHR], 2.11; 95% confidence interval [CI], 1.02–1.27), restriction (vs. normal; aHR, 1.40; 95% CI, 1.12–1.76), and percentage emphysema (highest vs. lowest quartile; aHR, 1.64; 95% CI, 1.03–2.61), but not greater high-attenuation areas or interstitial lung abnormalities. COVID-19 vaccination provided greater absolute risk reduction in these groups. Results were similar in participants without smoking, obesity, or clinical cardiopulmonary disease. Conclusions Prepandemic severe spirometric obstruction, spirometric restriction, and greater percentage emphysema lung on computed tomography were associated with risk of severe COVID-19. These findings support enhanced COVID-19 risk mitigation for individuals with impaired lung health and warrant further mechanistic studies on interactions of lung function, structure, and vulnerability to acute respiratory illnesses.

Abstract Objective The objective of this study was to examine the clinical outcomes during the implementation of a self-administered patient decision-aid (PtDA) for lupus. Methods We provided an effective computerized lupus PtDA in 15 rheumatology outpatient clinics 2019–2024 (including the COVID pandemic). We undertook Organizational Readiness to Implement Change Surveys (ORICs) and Team Learning and Psychological Safety Surveys (TLPSSs) at baseline. The primary study outcome objective measure, percent penetration/reach, was defined as the number of patients who viewed the lupus PtDA at the end of the study, divided by the total number of eligible patients (times 100). We used validated clinical personnel surveys to examine the perceived lupus PtDA appropriateness, acceptability, feasibility, success, and permanence, at 4 months, 12 months and 24 months post-PtDA implementation. Results Among the sites, the clinical personnels’ (n = 184) baseline ORIC commitment and efficacy scores (a 0–5 scale, higher = better) ranged from 3.5 to 4.2, and 3.4 to 4.4, respectively; the TLPSS scores (a 0–7 scale, higher = better) were 3.9–5.5 for internal learning, 3.7–5.6 for external learning, and 4.3–5.5 for psychological safety. The penetration (primary outcome) among 15 geographically diverse US rheumatology clinics ranged from 3% to 44%. We found that the total number of providers in the clinic was positively associated with higher penetration. Clinical personnel–perceived lupus PtDA outcomes were optimal at 4 months (all scale scores ranged from 1 to 5, higher = better): (i) appropriateness, 3.43 (s.d. 0.86); (ii) acceptability, 3.53 (s.d. 0.83); (iii) feasibility, 3.44 (s.d. 0.71); (iv) success, 3.41 (s.d. 0.73); and (v) permanence, 3.22 (s.d. 0.74). Conclusion We implemented a lupus PtDA with varied success rates during the COVID pandemic; more providers were associated with higher clinic penetration. Clinical personnel perceived high lupus PtDA appropriateness, acceptability, feasibility, success, and permanence that persisted up to 24 months. Trial Registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT03735238.

The role of second-look endoscopy and debridement (SLED) remains uncertain in children due to the perceived need for additional general anesthesia following their initial functional endoscopic sinus surgery (FESS) while mitigating risks and healthcare costs. This comprehensive review synthesizes current evidence on SLED in children, focusing on its practice pattern and treatment outcomes. This review was designed and performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Protocol. Independent queries of the PubMed Central, MEDLINE, and Bookshelf databases were performed. A total of 53 relevant, unique articles were initially identified; 12 articles were ultimately deemed appropriate for inclusion in final analysis. The most common indication for FESS was chronic rhinosinusitis or recurrent sinus infections while that for SLED under general anesthesia varied from institutional practice patterns to surgeon preference. No meaningful comparison of outcomes was possible as the “success rates” of FESS with or without SLED were largely based on unvalidated questionnaires and equally subjective surgeon assessments. Even when looking at outcomes based on revision rates, FESS with SLED was considered successful between 60.5% and 95.6% of the time, with a mean of 84.2%, while FESS without SLED was successful between 71.0% to 96.4% of the time, with a mean of 86.3%. However, no randomized, controlled studies were available in the pediatric literature pertaining to FESS with or without SLED. Moreover, it became apparent that previous conclusions on the utility of SLED were based on the outcomes of FESS following one single SLED under general anesthesia vs. no SLED. As such, there is an unmet need to examine the utility of serial, office-based SLED in children to better elucidate its utility in pediatric FESS.

Gastric cancer is a significant global health concern, with CDH1-associated gastric cancer representing a small but important subset of cases. Historically, individuals with CDH1 pathogenic germline variants were advised to undergo prophylactic total gastrectomy due to the high reported risk of gastric cancer and the limited sensitivity of upper endoscopy in detecting signet ring cell carcinoma (SRCC). However, emerging data suggest that the cumulative lifetime risk of advanced gastric cancer among CDH1 germline pathogenic variant carriers is lower than previously thought, and early-stage SRCC detected on endoscopy does not necessarily indicate imminent—or even eventual—progression to advanced cancer. The near-universal presence of T1a SRCC in gastrectomy specimens from asymptomatic CDH1 pathogenic variant carriers calls into question the reflexive recommendation for gastrectomy, including upon detection of SRCC during surveillance. Furthermore, the morbidity and quality-of-life impact associated with total gastrectomy require careful consideration. Active endoscopic surveillance has shown promise as an alternative management strategy for gastrectomy in patients lacking indicators of >T1a SRCC, though current data are limited by short follow-up periods and selection bias. This review synthesizes recent findings on the natural history of CDH1-associated gastric cancer and evaluates the risks and benefits of gastrectomy versus active endoscopic surveillance, with the goal of helping clinicians provide personalized and evidence-based recommendations for patients with CDH1 pathogenic variants.