Citations

Précis: Patients with clinically uncontrolled open angle glaucoma submitted to isolated gonioscopy-assisted transluminal trabeculotomy or combined with phacoemulsification not only achieved low mean IOPs, but also demonstrated stable IOP patterns during a 24-month follow-up. Purpose: To assess the impact of gonioscopy-assisted transluminal trabeculotomy (GATT) on long-term intraocular pressure (IOP) variation. Patients and Methods: An unicentric retrospective study including 169 consecutive patients who had undergone standalone GATT or combined with phacoemulsification (PHACOGATT) due to clinically uncontrolled open angle glaucoma, with at least 12 months of follow-up was conducted. Long-term mean IOP, long-term IOP peak, long-term IOP fluctuation, coefficient of variation, mean-positive IOP variation, sustained clinically significant positive IOP variation, and number of follow-up visits with IOP ≥15 mm Hg were investigated. Results: One hundred sixty-nine eyes from 169 patients were included (GATT group=101 patients; PHACOGATT group=68 patients). Mean long term IOP (12.0±1.8 vs. 11.2±2.0 mm Hg), mean long-term IOP peak (12.9±2.6 vs. 11.8±3.5 mm Hg), and mean coefficient of variation (0.07±0.08 vs. 0.05±0.09) were lower in the PHACOGATT group, while mean IOP fluctuation (1.0±3.7 vs. 1.2±1.8 mm Hg) was lower in the GATT group. In addition, the overall mean-positive IOP variation was 0.79±1.64 mm Hg. Finally, only 6.5% of the patients presented sustained clinically significant positive IOP variation and IOP was ≥15 mm Hg in 5.9% of the follow-up visits. Conclusions: Patients with clinically uncontrolled open angle glaucoma submitted to GATT or PHACOGATT achieved low mean IOPs and demonstrated stable IOP patterns. Our results provide additional evidence supporting GATT and PHACOGATT as viable options for the treatment of medically uncontrolled glaucoma patients requiring low and stable IOPs.

Extracellular vesicles (EVs) are lipid-bound vesicles secreted by cells, including exosomes, microvesicles, and apoptotic bodies. Proteomic analyses of EVs, particularly in relation to cancer, reveal specific biomarkers crucial for diagnosis and therapy. However, isolation techniques such as ultracentrifugation, size-exclusion chromatography, and ultrafiltration face challenges regarding purity, contamination, and yield. Contamination from other proteins complicates downstream processing, leading to difficulties in identifying biomarkers and interpreting results. Future research will focus on refining EV characterization for diagnostic and therapeutic applications, improving proteomics tools for greater accuracy, and exploring the use of EVs in drug delivery and regenerative medicine. In this review, we provide a bird’s eye view of various challenges, starting with EV isolation methods, yield, purity, and limitations in the proteome analysis of EVs for identifying protein targets.

OBJECTIVES: Acute hypoxemic respiratory failure in immunocompromised patients remains the leading cause of admission to the ICU, with high case fatality. The response to the initial oxygenation strategy may be predictive of outcome. This study aims to assess the response to the evolutionary profiles of oxygenation strategy and the association with survival. DESIGN: Post hoc analysis of EFRAIM study with a nonparametric longitudinal clustering technique (longitudinal K-mean). SETTING AND PATIENTS: Multinational, observational prospective cohort study performed in critically ill immunocompromised patients admitted for an acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1547 patients who did not require invasive mechanical ventilation (iMV) at ICU admission were included. Change in ventilatory support was assessed and three clusters of change in oxygenation modality over time were identified. Cluster A: 12.3% iMV requirement and high survival rate, n = 717 patients (46.3%); cluster B: 32.9% need for iMV, 97% ICU mortality, n = 499 patients (32.3%); and cluster C: 37.5% need for iMV, 0.3% ICU mortality, n = 331 patients (21.4%). These clusters demonstrated a high discrimination. After adjustment for confounders, clusters B and C were independently associated with need for iMV (odds ratio [OR], 9.87; 95% CI, 7.26–13.50 and OR, 19.8; 95% CI, 13.7–29.1). CONCLUSIONS: This study identified three distinct highly performing clusters of response to initial oxygenation strategy, which reliably predicted the need for iMV requirement and hospital mortality.

Introduction: High-power short-duration (HPSD) ablation has emerged as a promising alternative to conventional power delivery (CPD) for pulmonary vein isolation (PVI) among patients with atrial fibrillation (AF). However, its efficacy, procedural efficiency, and safety profile remain uncertain. Methods: PubMed, Embase, Cochrane Library and ClinicalTrials.Gov databases were systematically searched for randomized controlled trials (RCTs) comparing HPSD with CPD ablation for PVI in patients with AF. Random-effects models were used to pool hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI). R version 4.4.2 was used for statistical analysis. Results: Seven RCTs with 1,006 patients (514 HPSD, 489 CPD) were included. No significant differences were found in freedom from arrhythmia during the follow-up period (HR 0.77; 95% CI 0.41–1.45; p=0.424). AF recurrence did not differ (RR 0.94; 95% CI 0.65–1.36; p=0.733) between groups. HPSD had a significantly shorter procedural (MD -22.61 min; 95% CI -33.18, -12.04; p<0.001) and RF ablation times (MD -15.70 min; 95% CI -20.86, -10.55; p<0.001). No differences were observed in fluoroscopy time and first-pass isolation for right and left pulmonary veins. There was no difference in esophageal lesion rates, pericardial, or neurological complications, but there was a higher incidence of steam pops in HPSD (RR 3.42; 95% CI 1.45–8.09; p=0.005). Conclusion: In patients with AF undergoing PVI, HPSD did not increase freedom from arrhythmia as compared with CPD ablation, however it was associated with shorter procedure and RF ablation times with a similar safety profile.

Abstract Context Lipodystrophy syndromes are rare disorders characterized by deficient adipose tissue, leading to insulin resistance, dyslipidemia, and organ system abnormalities. Objective Our goal was to develop a lipodystrophy severity score (LDS) to holistically capture the diverse manifestations of lipodystrophy into a numerical score to aid in prediction of clinical outcomes and/or treatment impact. Design An 8-domain LDS was developed by 8 disease experts in consultation with patient organizations. The LDS was rated for feasibility and content validity by 28 additional clinicians and 9 patient representatives. LDS was compared to the Clinical Global Impression (CGI) of severity for 20 putative patient profiles, each at 2 different time points, and by comparing change in LDS to global impression of change. For external validation, LDS was calculated in 2 cohorts of patients with lipodystrophy treated with metreleptin. Results LDS domains include Diabetes/Insulin Resistance, Microvascular Complications of Diabetes, Lipids, Cardiovascular, Liver, Kidney, Reproductive, and Other. Each domain is assessed by 1 or more questions assessing both lifetime and recent complications of lipodystrophy. The LDS had high content validity and feasibility and high reliability by intraclass correlation coefficients (&gt;0.95). Global and domain-specific LDS were strongly correlated with CGI, as were changes in scores across visits (R = 0.79-0.99, P &lt; .001 for all). In generalized lipodystrophy, metreleptin significantly reduced LDS (from 46 to 26 at 12 months, P &lt; .001). The reductions were smaller in partial lipodystrophy (from 65 to 61 at 12 months, P = .04). Conclusion The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions.