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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

ABSTRACT Background Although Percutaneous Coronary Intervention (PCI) is the cornerstone treatment acute myocardial infarction (AMI), its use in the elderly, specifically nonagenarians patients, is not well studied. This study sought to compare the outcomes and complications of nonagenarian patients who experienced AMI between those who underwent PCI and those who underwent medical treatment only. Methods We evaluated 301,440 nonagenarian (ages 90−99) patients who presented to the hospital with AMI who were listed in the National Inpatient Sample from 2016 to 2021. AMI was defined according to the ICD‐10 Diagnostic Codes. Multivariable logistic regression analysis was used to examine the association of PCI with primary outcomes of mortality and secondary outcomes. The temporal trend of both the incidence of PCI in nonagenarian patients as well as the mortality rate between 2016 and 2021 were expressed as percentages over time. Results Of the total ( n = 301,440) nonagenarian patients with AMI, 33,035 patients underwent PCI while 268,406 did not undergo PCI and rather, just utilized optimized medical therapy (OMT). Of these, 3290 (9.96%) died in the PCI group, and 43580 (16.24%) died in the OMT group. All of the secondary outcomes were significantly different between the PCI and OMT groups. Comparing the two groups, the PCI group was associated with decreased mortality (OR 0.63 [95% CI, 0.58−0.69]; p < 0.001), acute heart failure (OR 0.88 [95% CI, 0.82−0.95] p < 0.001), and AKI (OR 0.75 [95% CI, 0.70−0.79]; p < 0.001), and increased cardiogenic shock (OR 3.06 [95% CI, 2.77−3.38]. The temporal of PCI in nonagenarian patients showed an increase in frequency from about 8.3 in 2016 to about 13.7% in 2021. Furthermore, comparing the mortality between the PCI and OMT groups showed a significant difference with a decreased mortality in the PCI group. Conclusions Nonagenarian patients experiencing AMI who underwent PCI is associated with a significant mortality decrease compared to those who underwent OMT only. The PCI group was also associated with a significant decrease in multiple secondary complications including acute heart failure, AKI, acute stroke, and an increase in cardiogenic shock. Temporally, we have seen an increase in PCI being used in nonagenarian patients over the interval.

Abstract While tissue-resident memory CD8+ T cells (TRM cells) provide superior frontline defense against pathogens, the molecular mechanisms governing their persistence and functional regulation remain poorly defined. Our study reveals that the costimulatory receptors CD27 and ICOS coordinately sustain PD-1high CD8+ TRM cell populations following resolution of acute influenza infection. These costimulatory signals serve as critical targets for PD-1/PD-L1 blockade, thereby facilitating the rejuvenation of PD-1high TRM cells and influencing the progression of fibrotic sequelae during the memory phase. Mechanistic dissection identifies the nuclear receptor Nur77 (NR4A1) as the convergent transcriptional hub downstream of CD27/ICOS, governing proliferative renewal and maintenance of PD-1high TRM cells. Therapeutic administration of a CD27 agonist not only amplified this TRM cell subset in late-stage memory but also conferred cross-protective immunity against heterosubtypic viral challenges. Clinically, the expression of CD27 and ICOS is enriched in CD8+ T cells within the lung tissues of patients with pulmonary fibrosis. Collectively, our findings establish the "CD27/ICOS-NR4A1-Proliferation" axis as a linchpin of PD-1/PD-L1-mediated TRM cell homeostasis, revealing druggable targets for intercepting infection-associated fibrotic progression.

Myocardial Bridging (MB) is typically a benign congenital coronary anomaly. MB can infrequently result in complications such as myocardial ischemia, arrhythmias, and sudden cardiac death. Recent studies suggest an underlying genetic component for MB involving DES, FBN1, SCN2B, or NOTCH1. The role of percutaneous coronary intervention (PCI) in managing MB, compared to optimal medical therapy (OMT), remains uncertain. Our study used the National Inpatient Sample (NIS) Database to identify patients aged 18 or older with myocardial bridging who were managed with PCI versus medical therapy. We compared the outcomes between both groups including in-hospital mortality, the trend of management of MB and other in-hospital outcomes or complications. Our results showed no statistically significant difference between both subgroups when comparing in-hospital mortality and secondary outcomes of cardiac arrest and the development of an acute kidney injury (AKI). Patients with myocardial bridging treated with PCI had a higher risk of developing cardiogenic shock, requiring LVAD, and requiring the use of intra-aortic balloon pump (IABP) compared to the medical therapy subgroup. Our study suggests the decision to perform PCI in myocardial bridging patients should be individualized such as in patients with refractory symptoms despite medical therapy or those with known high-risk features.

Summary Introduction Peroral plication of the esophagus (POPE) can reduce sump size and improve symptoms in end-stage achalasia. However, its long-term efficacy and safety are unknown. Methods Patients with end-stage achalasia who underwent POPE at our institution (2016–2024) were identified. Data were abstracted for patient demographics, procedural details, and clinical and radiographic outcomes. Results Twelve patients underwent POPE. The technical success rate was 100%, with mean procedural time of 57 minutes and without adverse events. Symptomatic improvement occurred in 75% of patients (mean follow-up of 15 months), while 86% had radiographic improvement in sump size. Repeat POPE in 6 (50%) patients a mean of 2.6 years after index POPE and a third POPE in four (33%) patients a mean of 3.1 years later was performed, with similar technical success rates and outcomes to the index POPE. Conclusions POPE is a safe and repeatable long-term therapeutic option in end-stage achalasia.

Précis: 240-degree and 360-degree goniotomy (GT) demonstrated similar efficacy in intraocular pressure (IOP) reduction, both outperforming 120-degree GT in patients with juvenile open angle glaucoma (JOAG) at postoperative 6-month follow-up. Objective: To compare the surgical efficacy and safety of 120-degree, 240-degree, and 360-degree GT for patients with JOAG. Patients and Methods: This multicenter retrospective study included 102 eyes of 102 patients with JOAG, who underwent GT with a follow-up of at least 6 months. Patients were categorized into 3 groups: (1) 120-degree GT, (2) 240-degree GT, and (3) 360-degree GT. IOP, glaucoma medications, and complications were recorded at baseline and the final visit. Complete success and qualified success were defined as a postoperative IOP ≤21 mm Hg without and with medications, respectively. Results: Mean age of the participants was 24.4 ± 7.9 years. After a mean follow-up of 8.1 ± 2.7 months, complete success rates were similar between the 240-degree GT (45.2%) and the 360-degree GT (63.2%; P = 0.135), and both were superior to 120-degree GT (18.2%; P < 0.05). Qualified success rates among patients in the 120-degree, 240-degree, and 360-degree GT groups were 93.9%, 96.8%, and 100%, respectively, and showed no statistically significant difference (P = 0.292). 360-degree GT required fewer medications than 240-degree GT and 120-degree GT (P < 0.05), with no significant difference in medications between 120-degree GT and 240-degree GT (P > 0.05). Hyphema was the most common postoperative complication, with a significantly higher incidence in the 360-degree GT (68.4%) compared with the 240-degree GT (41.9%) and 120-degree GT (33.3%; P < 0.05). Conclusions: 240-degree and 360-degree GT showed similar efficacy in IOP reduction and were superior to 120-degree GT. More extensive GT may provide better outcomes in JOAG.

ABSTRACTBackgroundMyeloproliferative neoplasms (MPN) are associated with an increased cardiovascular risk including acute coronary syndrome. However, there is a lack of comprehensive data regarding the rate of percutaneous coronary intervention (PCI), as well as the in‐hospital characteristics and outcomes for MPN patients.AimsWe aimed to evaluate the temporal trends and outcomes of PCI among patients with MPN.Methods and ResultsThe National Inpatient Sample database from 2016 to 2020 was queried to identify all PCI hospitalizations. Temporal trends and outcomes of patients with and without MPN following PCI were analyzed. Propensity score matching (PSM) was implemented to compare outcomes between MPN and non‐MPN groups. 2,237,210 PCI hospitalizations with 7560 (0.27%) patients with MPN were included in this study. Throughout the study period, the prevalence of MPN among PCI admissions remained stable (p‐value for trend = 0.12). Within the MPN subgroup, essential thrombocythemia (ET) was the predominant condition (53.2). Patients with MPN had higher prevalence of cardiovascular comorbidities than non‐MPN patients. Following PSM, MPNs were significantly associated with a higher risk of blood transfusions (OR: 1.66, 95% CI: 1.22−2.24, p = 0.001) and AKI (OR: 1.39, 95% CI: 1.17−1.65, p < 0.001). In contrast, the risk of in‐hospital mortality (OR: 1.18, 95% CI: 0.83−1.69, p = 0.354 and bleeding (OR: 1.43, 95% CI: 0.90−2.27, p = 0.127) did not significantly differ between the two groups.ConclusionsOur study demonstrated that while the prevalence of MPN among patients undergoing PCI remained stable, those with MPN faced higher risks of bleeding, blood transfusion and acute kidney injury. Further research is warranted to explore the underlying reasons for these increased risks and to improve outcomes in this high‐risk group.

Background: Immune cell–driven inflammation is a key mediator of metabolic dysfunction–associated steatohepatitis (MASH) progression. We have previously demonstrated that pharmacological sphingosine 1-phosphate (S1P) receptor modulation ameliorates MASH and is associated with attenuated accumulation of intrahepatic macrophage and T-cell subsets. Although S1P receptors are expressed on several immune cell types, given the prominent role of monocyte-derived recruited macrophages in the sterile inflammation of MASH, we hypothesized that deletion of S1P receptor 1 (S1P 1 ) on myeloid cells may ameliorate MASH by reducing the accumulation of proinflammatory monocyte-derived macrophages in the liver. Methods: The LyzMCre approach was used to generate myeloid cell–specific knockout mice, termed S1pr1 MKO . Littermate S1pr1 loxp/loxp mice were used as wild-type controls. MASH was established by feeding mice a high-fat, -fructose, and -cholesterol (FFC) diet for 24 weeks, which led to the development of steatohepatitis and MASH-defining cardiometabolic risk factors. Liver injury and inflammation were determined by histological and gene expression analyses. Intrahepatic leukocyte populations were analyzed by mass cytometry and immunohistochemistry. Results: Histological examination demonstrated a reduction in liver inflammatory infiltrates and fibrosis in high-fat, -fructose, and -cholesterol–fed S1pr1 MKO compared to wild-type. There was a corresponding reduction in alanine aminotransferase, a sensitive marker for liver injury. As determined by mass cytometry, a significant decrease in recruited macrophages was noted in the livers of high-fat, -fructose, and -cholesterol–fed S1pr1 MKO mice compared to wild-type. Gene ontology pathway analysis revealed significant suppression of the peroxisome proliferator–activated receptor gamma and mitogen-activated protein kinase pathways in S1pr1 MKO consistent with attenuated MASH in mice. Conclusions: Deletion of S1P 1 in myeloid cells is sufficient to attenuate intrahepatic accumulation of monocyte-derived macrophages and ameliorate murine MASH.