Citations

Abstract Purpose To assess intra‐ (repeatability) and inter‐observer (reproducibility) variability of laser speckle flowgraphy (LSFG) for retinal blood flow (RBF) measurement in 20 eyes of wild type (C57BL/6J) mice and effect of intravitreal Aflibercept on RBF in optic nerve head (ONH) region of 10 eyes of Ins2 (Akita) diabetic mice. Methods ‘Mean blur rate (MBR)’ was measured for all quadrants of tissue area (MT), vessel (MV) and total area (MA) of ONH region. Changes in MT were analysed at each timepoint. Repeatability was evaluated by measuring MBR variability without changing mouse head position, and reproducibility after resetting mouse head position by another operator. Coefficient of repeatability (CR) through Bland–Altman plot method coefficient of variation (COV) and Intraclass correlation coefficient (ICC) was calculated. Intravitreal Aflibercept (1 μg) was administered to Akita eyes and intraocular pressure (IOP) was measured using a tonometer at baseline, day 7, 14, 21 and 28 post‐injection. Hurvich and Tsai's criterion was used. Results Coefficient of repeatability values of repeatability and reproducibility for all quadrants were within limits of agreement. Reliability was excellent (ICC 0.98–0.99) and reproducibility was moderate to excellent (ICC 0.64–0.96). There was a non‐significant IOP increase in all Akita eyes at Day 28 ( p > 0.05), and significant increase in MT in all quadrants at Day 21 and superior, inferior and temporal quadrants at Day 28 ( p < 0.05). Conclusion Laser speckle flowgraphy demonstrates excellent repeatability and moderate to excellent reproducibility in measuring RBF. Intravitreal Aflibercept injection results in a significant increase in MT up to 28 days post‐injection without significant increase in IOP.

Abstract Emerging studies have identified the critical roles of tissue-resident memory CD8+ T (TRM) and B (BRM) cells in the protection against mucosal viral infections, but the underlying mechanisms regulating robust development of TRM and BRM cells remain incompletely understood. We have recently shown that tissue-resident helper CD4+ T (TRH) cells, developed following influenza virus infection, function to sustain the optimal maintenance of TRM and BRM cells at the mucosal surface. In this study, we have explored the cellular and molecular cues modulating lung TRH persistence after influenza infection in C57BL/6 mice. We found that TRH cells were colocalized in tertiary lymphoid structures (TLSs) with local B cells. Abolishing TLSs or the depletion of B cells impaired lung TRH cell numbers. Of note, we found that persistent TCR signaling is needed for the maintenance of TRH cells after the clearance of infectious influenza virus. Furthermore, selective ablation of B cell–derived MHC class II resulted in partial reduction of lung TRH cell number after influenza infection. Our findings suggest that the interaction between lung-resident TRH cells and B cells, along with persistent Ag stimulation, is required to maintain TRH cells after respiratory viral infection.

AbstractBackgroundThe real‐world data on the safety profile of transvenous lead extraction (TLE) for infected cardiac implantable electronic devices (CIED) among elderly patients is not well‐established. This study aimed to evaluate the hospital outcomes between patients of different age groups who underwent TLE for infected CIED.MethodUsing the Nationwide Readmissions Database, our study included patients aged ≥18 years who underwent TLE for infected CIED between 2017 and 2020. We divided the patients into four groups: Group A. Young (<50 years), Group B. Young intermediate (50–69 years old), Group C. Older intermediate (70–79 years old), and Group D. Octogenarian (≥80 years old). We then analyzed the in‐hospital outcome and 30‐day readmission between these age groups.ResultsA total of 10,928 patients who were admitted for TLE of infected CIED were included in this study: 982 (9.0%) patients in group A, 4,234 (38.7%) patients in group B, 3,204 (29.3%) patients in group C and 2,508 (23.0%) of patients in group D. Our study demonstrated that the risk of early mortality increased with older age (Group B vs. Group A: OR: 1.92, 95% CI: 1.19‐3.09, p < .01; Group C vs. Group A: OR: 2.47, 95% CI: 1.51‐4.04, p < .01; Group D vs. Group A: OR: 2.82, 95% CI: 1.69‐4.72, p < .01). The risk of non‐home discharge also increased in elderly groups (Group B vs. Group A: OR: 1.89; 95% CI: 1.52‐2.36; p < .01; Group C vs. Group A: OR: 2.82; 95% CI 2.24‐3.56; p < .01; Group D vs. Group A: OR: 4.16; 95% CI: 3.28‐5.28; p < .01). There was no significant difference in hospitalization length and 30‐day readmission between different age groups. Apart from a higher rate of open heart surgery in group A, the procedural complications were comparable between these age groups.ConclusionElderly patients had worse in‐hospital outcomes in early mortality and non‐home discharge following the TLE for infected CIED. There was no significant difference between elderly and non‐elderly groups in prolonged hospital stay and 30‐day readmission. Elderly patients did not have a higher risk of procedural complications.

AbstractBackgroundThe real‐world data on the safety profile of ventricular tachycardia (VT) ablation among elderly patients is not well‐established. This study aimed to evaluate the procedural outcomes among those aged 18–64 years versus those aged ≥65 years who underwent catheter ablation of VT.MethodUsing the Nationwide Readmissions Database, our study included patients aged ≥18 years who underwent VT catheter ablation between 2017 and 2020. We divided the patients into non‐elderly (18–64 years old) and elderly age groups (≥65 years old). We then analyzed the in‐hospital procedural outcome and 30‐day readmission between these two groups.ResultsOur study included 2075 (49.1%) non‐elderly patients and 2153 (50.9%) elderly patients who underwent VT ablation. Post‐procedurally, elderly patients had significantly higher rates of prolonged index hospitalization (≥7 days; 35.5% vs. 29.3%, p < .01), non‐home discharge (13.4% vs. 6.0%, p < .01), 30‐day readmission (17.0% vs. 11.4%, p < .01), and early mortality (5.5% vs. 2.4%, p < .01). There was no significant difference in the procedural complications between two groups, namely vascular complications, hemopericardium/cardiac tamponade, cerebrovascular accident (CVA), major bleeding requiring blood transfusion, and systemic embolization. Through multivariable analysis, the elderly group was associated with higher odds of early mortality (OR: 7.50; CI 1.86–30.31, p = .01), non‐home discharge (OR: 2.41; CI: 1.93–3.00, p < .01) and 30‐day readmission (OR: 1.58; CI 1.32–1.89, p < .01).ConclusionElderly patients have worse in‐hospital outcome, early mortality, non‐home discharge, and 30‐day readmission following catheter ablation for VT. There was no significant difference between elderly and non‐elderly groups in the procedural complications.

Background: While spontaneous coronary artery dissection (SCAD) patients can present with ventricular arrhythmias (VAs), the in-hospital outcomes among these patients are not well-established. Objective: This study aimed to analyze the in-hospital outcomes of patients with SCAD and concurrent VAs, and to determine the predictors of VAs occurrence in this population. Methods: Using the Nationwide Readmissions Database, our study included patients aged 18 years or older who had SCAD between 2017 and 2020. We categorized the cohort into two groups depending on the presence of VAs during hospitalization. The in-hospital outcomes were assessed between two groups. Through multivariable analysis, we further analyzed the predictors of VAs occurrence among SCAD patients. Results: Our study included 160 (13.45%) SCAD patients with concurrent VAs and 1,030 (86.55%) SCAD patients without concurrent VAs between 2017 and 2020. SCAD patients with concurrent VA were associated with higher rates of early mortality (11.88% vs. 2.04%, p<0.01), prolonged index hospital stay (≥7 days) (31.25% vs. 12.82%, p<0.01), and non-home discharge (21.88% vs. 6.50%, p<0.01). The length of hospital stay was longer in the SCAD with concurrent VAs group (6.93 days vs. 3.73 days, p<0.01), and the median cumulative cost of hospitalization was also higher in this group ($31,450 vs. $14,664, p<0.01). SCAD with concurrent VAs patients also had poorer in-hospital adverse events. In multivariable analysis, the independent predictors for VAs occurrence among SCAD patients were chronic liver disease (aOR: 2.18; 95% CI: 1.15- 4.12, p=0.02) and heart failure (aOR: 3.40; 95%CI: 2.30- 5.02, p<0.01). Conclusion: Ventricular arrhythmias among SCAD patients were associated with poorer in-hospital outcomes. Heart failure and chronic liver disease were the predictors of VAs in SCAD patients. This highlights the importance of closely monitor and aggressive VAs management among these high-risk patients.

Background: Catheter ablation for ventricular tachycardia (VT) has been increasingly performed. While it is estimated that 42% of adults in the United States are obese, the impact of obesity on VT ablation procedures remains unclear. Objective: This study aimed to evaluate the procedural outcomes and 30-day readmission among non-obese and obese patients who underwent catheter ablation of VT. Method: Using the Nationwide Readmissions Database, our study included patients aged 18 years or older who underwent catheter ablation for VT between 2017 and 2020. The study cohort was stratified into non-obese (BMI < 30kg/m 2 ) and obese (BMI ≥ 30kg/m 2 ). The in-hospital procedural outcome and 30-day readmission were analyzed between these groups. Results: Our study included a total of 835 obese patients (19.7%) and 3393 non-obese patients (80.3%). Obese group had a higher rate of prolonged length of stay (>7 days) (37.6% vs 31.2%, p<0.01) and a higher cost of hospitalization ($39 983 vs $37 015, p<0.01). Overall, there were no significant differences in early mortality (4.5% vs 3.8%, p=0.45). Apart from increased vascular complications in the obese group (1.8% vs 0.9%, p=0.03), there were no significant differences in other procedural complications between both groups. There were no significant differences in 30-day readmission rates between obese and non-obese groups (15.5% vs 14.1%, p=0.38). Additional analysis performed in the obese group revealed a non-significant decreasing trend in early mortality rate post-procedurally (5.4% to 4.8%, P trend = 0.66). On multivariable analysis, heart failure was associated with a higher risk of 30-day readmission in obese patients (OR: 2.00; 95% CI: 1.01-3.99; p=0.05). Conclusion: Our study suggests that catheter ablation for VT can be performed relatively safely in obese patients without significant differences in 30-day mortality and readmission outcomes. Patients should not be excluded from VT ablation on the basis of obesity.

Background: Despite the optimal efficacy of catheter ablation for ventricular tachycardia (VT), recurrence of VT can occur post-procedurally. However, data on the high-risk population for VT recurrence and the in-hospital outcomes remain scarce. Objective: This study aimed to determine the predictors of 30-day readmission for recurrent VT after catheter ablation of VT and assess the in-hospital outcomes. Method: Using the all-payer, nationally representative Nationwide Readmissions Database, we identified the patients aged ≥18 years who underwent catheter ablation for VT and were readmitted within 30 days because of recurrent VT from 2017 to 2020. We performed unweighted univariable and multivariable analyses to determine the outcomes and to identify the patient and hospital variables that were predictive of 30-day readmissions for recurrent VT. A p-value of <0.05 is considered statistically significant. Results: In our analysis, a total of 4,102 patients were discharged alive after VT ablation, of which 278 (6.8%) were readmitted within 30 days for recurrent VT. Recurrent VT was also the most common cause of 30-day readmission (47.7%, n=278/583). Compared to non-recurrent VT readmission, readmission due to recurrent VT had higher mortality during rehospitalization (7.55% vs 3.72%, p<0.01) and higher cumulative hospitalization cost ($57584 vs $37846, p<0.01). Via multivariable analysis, congestive heart failure (aOR: 1.84; 95% CI: 1.07-3.17; P=0.03) and non-elective index admissions (aOR: 1.88; 95% CI: 1.32-2.68; P<0.01) were the independent predictors of 30-day readmission for recurrent VT. Conclusion: Recurrent VT was the most common cause of 30-day readmission following VT ablation. Congestive heart failure and non-elective index admissions were the independent predictors of 30-day readmissions for recurrent VT. These highlight the importance of further research in ablation strategies to improve the efficacy of VT ablation.

Background: Catheter ablation for ventricular tachycardia (VT) has been increasingly performed over the past decades. However, the real-world data on the safety profile of this procedure among elderly patients is limited. Objective: This study aimed to evaluate the procedural outcomes and 30-day readmission among those aged 18-64 years versus those aged ≥65 years who underwent catheter ablation of VT. Method: Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged 18 years or older who underwent VT catheter ablation between 2017 and 2020. We divided the patients into non-elderly (18-64 years old) and elderly age groups (≥65 years old). We then analyzed the in-hospital procedural outcome and 30-day readmission between these groups. Results: Our study included 2075 (49.1%) non-elderly patients and 2153 (50.9%) elderly patients who underwent VT ablation. Following the procedure, elderly patients had significantly higher rates of prolonged index hospitalization (≥7 days) (35.5% vs 29.3%, p<0.01), non-home discharge (13.4% vs 6.0%, p<0.01), 30-day readmission (17.0% vs 11.4%, p<0.01), and early mortality (5.5% v 2.4%, p<0.01). The median cumulative cost of hospitalization was significantly higher in the elder groups ($40,230 vs. $37,612, p ≤0.01). There was no significant difference in the procedural complications between the two groups. Through multivariable analysis, the elderly group was associated with significantly higher odds of early mortality (OR: 7.50; CI 1.86 - 30.31, p=0.01), non-home discharge (OR: 2.41; CI: 1.93 - 3.00, p<0.01) and 30-day readmissions (OR: 1.58; CI 1.32 - 1.89, p<0.01). Conclusion: Our study suggests that elderly patients have poorer in-hospital outcome in early mortality, non-home discharge and 30-day readmissions following catheter ablation for VT. There was no significant difference between elderly and non-elderly groups in the procedural complications.

Abstract The long-term physiological consequences of SARS-CoV-2, termed Post-Acute Sequelae of COVID-19 (PASC), are rapidly evolving into a major public health concern. The underlying cellular and molecular etiology remain poorly defined but growing evidence links PASC to abnormal immune responses and/or poor organ recovery post-infection. Yet, the precise mechanisms driving non-resolving inflammation and impaired tissue repair in the context of PASC remain unclear. With insights from three independent clinical cohorts of PASC patients with abnormal lung function and/or viral infection-mediated pulmonary fibrosis, we established a clinically relevant mouse model of post-viral lung sequelae to investigate the pathophysiology of respiratory PASC. By employing a combination of spatial transcriptomics and imaging, we identified dysregulated proximal interactions between immune cells and epithelial progenitors unique to the fibroproliferation in respiratory PASC but not acute COVID-19 or idiopathic pulmonary fibrosis (IPF). Specifically, we found a central role for lung-resident CD8+ T cell macrophage interactions in maintaining Krt8hi transitional and ectopic Krt5+ basal cell progenitors, thus impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Mechanistically, CD8+ T cell derived IFN-γ and TNF stimulated lung macrophages to chronically release IL-1β, resulting in the abnormal accumulation of dysplastic epithelial progenitors and fibrosis. Notably, therapeutic neutralization of IFN-γ and TNF, or IL-1β after the resolution of acute infection resulted in markedly improved alveolar regeneration and restoration of pulmonary function. Together, our findings implicate a dysregulated immune-epithelial progenitor niche in driving respiratory PASC. Moreover, in contrast to other approaches requiring early intervention, we highlight therapeutic strategies to rescue fibrotic disease in the aftermath of respiratory viral infections, addressing the current unmet need in the clinical management of PASC and post-viral disease.

Surgery has long been an important treatment for limiting optic nerve damage and minimising visual loss in patients with glaucoma. Numerous improvements, modifications, and innovations in glaucoma surgery over recent decades have improved surgical safety, and have led to earlier and more frequent surgical intervention in glaucoma patients at risk of vision loss. This review summarises the latest advancements in trabeculectomy surgery, glaucoma drainage device (GDD) implantation, and minimally invasive glaucoma surgery (MIGS). A comprehensive search of MEDLINE, EMBASE, and CENTRAL databases, alongside subsequent hand searches—limited to the past 10 years for trabeculectomy and GDDs, and the past 5 years for MIGS—yielded 2283 results, 58 of which were included in the final review (8 trabeculectomy, 27 GDD, and 23 MIGS). Advancements in trabeculectomy are described in terms of adjunctive incisions, Tenon’s layer management, and novel suturing techniques. Advancements in GDD implantation pertain to modifications of surgical techniques and devices, novel methods to deal with postoperative complications and surgical failure, and the invention of new GDDs. Finally, the popularity of MIGS has recently promoted modifications to current surgical techniques and the development of novel MIGS devices.