Citations

Background The optimal imaging guidance for percutaneous coronary intervention (PCI) in complex coronary lesions remains a matter of debate. This meta-analysis compares the efficacy and safety of optical coherence tomography (OCT)-guided PCI versus angiography-guided PCI. Methods Following PRISMA guidelines, we systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov from inception to December 2024. Randomized controlled trials (RCTs) comparing OCT-guided PCI to angiography-guided PCI were included. Data analysis was performed using RevMan 5.4, with risk ratios (RR) and 95% confidence intervals (CI) calculated for dichotomous outcomes using a random-effects model. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Results Eleven RCTs involving 6432 participants were included. OCT-guided PCI showed no statistically significant reduction in all-cause mortality compared to angiography-guided PCI (RR 0.72, 95% CI 0.51–1.01, P = 0.06, I 2 = 0%). However, OCT-guided PCI was associated with a significant reduction in cardiac death (RR 0.52, 95% CI 0.30–0.90, P = 0.02, I 2 = 0%), major adverse cardiovascular events (MACE) (RR 0.70, 95% CI 0.55–0.89, P = 0.003, I 2 = 0%), stent thrombosis (RR 0.53, 95% CI 0.33–0.87, P = 0.01, I 2 = 0%), and major edge dissection (RR 0.47, 95% CI 0.34–0.65, P < 0.00001, I 2 = 0%). Upon stratification of studies on the basis of follow-up duration, similar results were noted. Conclusion OCT-guided PCI demonstrated significant benefits in reducing cardiac death, MACE, and procedural complications compared to angiography-guided PCI. These findings support the integration of OCT in complex PCI, although further studies are warranted to assess its impact on long-term mortality.

ABSTRACT Background : Tirofiban is a GP IIb/IIIa inhibitor, an anti‐platelet drug that is used in ischemic stroke or acute coronary syndromes. The goal of this study is to assess the safety and efficacy of the drug in patients who have suffered an acute ischemic stroke. Methods : A comprehensive search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to December 2025 yielded randomized controlled trials (RCTs) comparing Tirofiban and conventional management in patients with acute ischemic stroke. We assessed the risk of bias using the revised Cochrane “Risk of bias” tool for randomized trials (RoB 2.0). We analyzed the outcomes using RevMan 5.4, with risk ratio (RR) as the effect measure. Results : A total of 9 RCTs with 4210 patients were included in our meta‐analysis. According to our meta‐analysis, the tirofiban group was associated with a statistically significant increase in the patients showing functional independence at 90 days, measured by patients with Modified Rankin Score (mRS) of 0–2 (RR 1.13; CI = 1.06–1.20) and excellent outcome (mRS score 0–1) at 90 days (RR 1.17; CI = 1.05–1.29). We found no statistically significant difference between the two groups regarding mortality (RR 0.94; CI = 0.63–1.40). The tirofiban group had an increased incidence of intracranial hemorrhage (ICH) (RR 1.25; CI = 1.06–1.47) but had a similar incidence of symptomatic ICH as compared to the control group (RR 1.48; CI = 0.98–2.24). Conclusion : This meta‐analysis suggests that tirofiban may improve favorable functional outcomes (mRS 0–2) in acute ischemic stroke, although the certainty of evidence was moderate. While no significant increase in sICH was observed, some analyses showed a higher rate of overall intracranial hemorrhage. These findings should therefore be interpreted cautiously, and further high‐quality randomized trials are needed to confirm the efficacy and safety of tirofiban before routine guideline use.

Background: Vitamin C is a vital nutrient that functions as an antioxidant and is important as a co-factor and regulator of several immune system pathways. The role of vitamin C in the treatment of COVID-19 is largely debatable. We conducted this meta-analysis to evaluate the efficacy and safety of vitamin C in the treatment of COVID-19. Methods: We searched several electronic databases from inception to March 2023 to retrieve randomized controlled trials on the use of vitamin C for COVID-19. RevMan 5.4 was used to calculate risk ratios (RRs) and mean differences (MDs) along with confidence intervals (95% CI) using a random-effects model. Results: We included nine randomized controlled trials in our meta-analysis. Vitamin C did not reduce the all-cause mortality in patients with COVID-19 compared to the standard treatment (RR 0.92, 95% CI: 0.83–1.02; I 2 = 1%). Vitamin C was found to be associated with a similar incidence of ventilation in COVID-19 patients when compared to standard treatment (RR 0.98, 95% CI: 0.87–1.11, I 2 = 0%). There were no significant differences between both groups regarding the incidence of hospitalization (RR 1.00, 95% CI: 0.98–1.02; I 2 = 0%), incidence of recovery (RR 1.57, 95% CI: 0.45–5.50; I 2 = 52%), hospital mortality (RR 0.68, 95% CI: 0.44–1.06; I 2 = 0%) and length of hospital stay (MD −0.63, 95% CI: −3.04 to 1.78; I 2 = 81%). Conclusion: Vitamin C administration did not reduce all-cause mortality in COVID-19 patients. Additional studies are required to evaluate the role of vitamin C in the prevention and treatment of COVID-19 especially in ICU patients.

Background: Transradial artery access (TRA) is the favored approach for percutaneous coronary intervention (PCI) and coronary angiography (CAG). However, transulnar artery access (TUA) has emerged as an alternative, particularly when TRA is not feasible. This systematic review and meta-analysis aims to compare the efficacy and safety of TUA versus TRA in patients undergoing PCI and CAG. Methods: From inception to August 2025, a systematic search of electronic databases was conducted. Data were synthesized using a random-effects model, and heterogeneity was assessed using the I 2 statistic. Results: Nine RCTs involving 6089 patients were included. Meta-analysis revealed no significant difference in procedural success between TUA and TRA (RR: 0.93, 95% CI: 0.82–1.06, P = 0.28, I 2 = 99%). Similarly, puncture success rates were comparable (RR: 0.95, 95% CI: 0.91–1.00, P = 0.06, I 2 = 83%). Secondary outcomes showed no significant differences in puncture attempts or hematoma incidence, but TRA was associated with a shorter procedure time (MD: 0.89, 95% CI: 0.27–1.50, P = 0.005). Conclusion: TUA provides a viable alternative to TRA, with similar success rates and complication profiles. However, TRA remains superior in terms of procedure time. Further large-scale RCTs are warranted to confirm these findings and refine clinical guidelines.

Abstract Clinical flow cytometry laboratories are facing rising test volumes, greater assay complexity, and increasing requirements for quality control and assay validation. In response, the International Clinical Cytometry Society (ICCS) conducted a workload survey in early 2023 to gather updated information on assay volumes, complexity, staffing, and technology. Data analysis focused on identifying correlations between length of time to introduce new assays and other factors as a means to gain insight about laboratories that seem to be either adapting or struggling. Flow cytometry assays were categorized into 3 levels of technical/interpretative complexity: high (e.g., measurable/minimal residual disease (MRD assays)), moderate (e.g., leukemia/lymphoma assays (Assays L&L ), excluding MRD assays), and low (e.g., CD4 count). Annual assays per staff member were calculated according to staff involved in case sign‐out (Staff Signout ) or other laboratory operations (Staff LabOps ). Respondents were from 101 laboratories in the United States (69.3%), Canada (4.0%), and other countries (26.7%). Low, moderate, and high technical/interpretative complexity assays were performed in 85.1%, 97.0%, and 47.5% of all laboratories, respectively. Median annual total assays (Assays Total ) per laboratory were 3515 and, based on complexity, were 1518.5 (low), 1808.8 (moderate), and 350 (high). Among all laboratories, the median time (interquartile range) to introduce new Assays L&L was 6 mos. (4–12 mos.), to introduce MRD assays was 11 mos. (5–12 mos.), and to validate/go‐live with new cytometers was 8 mos. (4–12 mos.); these times positively correlated with each other. This study confirmed significantly increased workload since the prior ICCS 2013 workload survey with a concurrent decrease in Staff LabOps . Faster introduction of new assays correlated with other successes, including quicker validation of and going live with new cytometers. Among all laboratories, those that performed myeloid MRD assays versus those that did not were also found to be faster to introduce new assays. The need for sufficient staffing has been emphasized because laboratories with both higher annual volumes of myeloma MRD assays and higher ratios of Assays Total per Staff LabOps were slower to introduce new assays. “Lack of staff and/or time dedicated or protected for assay development” and, more generally, “staff number” were the most commonly identified major barriers for new assay development, with the former specifically linked to slower introduction of new assays among all laboratories.

Background/objective: HCM is a structural disorder of the myocardium that leads to sudden cardiac death in young adults. We synthesized an updated understanding of the role of Cardiac Myosin Inhibitors (CMIs) in HCM by pooling data from RCTs. Methods: We identified six published RCTs, involving 826 participants. Data were extracted pertaining to study characteristics; primary outcomes of interest–(1) change from baseline in resting left ventricular outflow tract (LVOT) peak gradient, (2) change from baseline in Valsalva LVOT peak gradient, and (3) improvement of ≥1 NYHA class–and secondary outcomes. These were pooled using Review Manager 5.4, employing a random-effects model, and reported as odds ratios (ORs) or mean differences (MDs). Results: We found statistically significant between-group difference favoring CMIs in change from baseline in LVOT peak gradient: at rest (MD −39.33; −53.01 to −25.64), post-Valsalva (MD −48.99; −53.96 to −44.03), and post-exercise (MD −37.11; −44.34 to −29.87); ≥1 NYHA class improvement (OR 4.10; 2.79–6.02), change from baseline in peak oxygen uptake (MD −37.11; −44.34 to −29.87), LVOT gradient ≤30 mm hg (RR 14.89; 7.47–29.67), participants eligible for septal reduction therapy (RR 0.26; 0.18–0.36), and change from baseline in KCCQ-CSS score (MD 8.54; 5.36–11.71). Subgrouping by intervention type (mavacamten vs. aficamten) revealed non-significant results for all primary outcomes. Conclusions: CMIs can contribute to improving key efficacy outcomes for patients with HCM while reducing incidence of SRT.

Background/Objectives: The enzyme ubiquitin-specific protease 44 (USP44) is a deubiquitinating enzyme with identified physiological roles as a tumor suppressor and an oncogene. While some binding partners and substrates are known for USP44, the identification of other interactions may improve our understanding of its role in cancer. We therefore performed a proximity biotinylation study that identified products of several known cancer genes that are associated with USP44, including a novel interaction between BRCA2 and USP44. Methods: We expressed a fusion protein that linked USP44 and mutant Escherichia coli biotin ligase BioID in SH-SY5Y neuroblastoma cells. Control experiments were performed using BioID alone. In duplicate experiments, cells were pulsed with biotin and biotinylated proteins were isolated under denaturing conditions and the proteins were identified by mass spectrometry. The resulting list of proteins were analyzed using Enrichr and cross-referenced with the COSMIC Cancer Gene Census. We validated the association with BRCA2 using immunoprecipitation. The role of USP44 in the Fanconi anemia DNA repair pathway was investigated using chromosome analysis of wild-type or Usp44-knockout cells after exposure to mitomycin C. Results: We identified 146 proteins that were selectively retrieved by the USP44 construct and compared with cells expressing the BioID ligase alone, including 15 gene products encoded by genes on tier 1 of the COSMIC Cancer Gene Census, including BRCA2. The association between USP44 and BRCA2 was validated through immunoprecipitation. We tested the functional role of USP44 in the Fanconi anemia DNA repair pathway through chromosome breakage analysis and found that cells lacking USP44 had a significant increase in chromosome breaks and radial chromosomes. We found that high BRCA2 transcript was correlated with poor survival in neuroblastoma, likely due to its tight association with proliferation in these tumors. Conclusions: Our results identified novel potential binding partners and potential substrates for USP44, including several with direct roles in cancer pathogenesis. Our results identified a novel association between BRCA2 and USP44, and a previously unknown role for USP44 in the Fanconi anemia DNA repair pathway that may contribute to its role in cancer.

Abstract Neuroblastoma is an embryonic cancer that contributes disproportionately to death in young children. Sequencing data have uncovered few recurrently mutated genes in this cancer, although epigenetic pathways have been implicated in disease pathogenesis. We used an expression-based computational screen that examined the impact of deubiquitinating enzymes on patient survival to identify potential new targets. We identified the histone H2B deubiquitinating enzyme USP44 as the enzyme with the greatest impact on survival in patients with neuroblastoma. High levels of USP44 significantly correlate with metastatic disease, unfavorable histology, advanced patient age, and MYCN amplification. The subset of patients with tumors expressing high levels of USP44 had significantly worse survival, including those with tumors lacking MYCN amplification. We showed experimentally that USP44 regulates neuroblastoma cell proliferation, migration, invasion, and neuronal development. Depletion of the histone H2B ubiquitin ligase subunit RNF20 resulted in similar findings, strongly implicating this histone mark as the target of USP44 activity in this disease. Integration of transcriptome and epigenome in analyses demonstrates a distinct set of genes that are regulated by USP44, including those in Hallmark MYC target genes in both murine embryonic fibroblasts and the SH-SY5Y neuroblastoma cell line. We conclude that USP44 is a novel epigenetic regulator that promotes aggressive features and may be a novel target in neuroblastoma. Implications: This study identifies a new genetic marker of aggressive neuroblastoma and identifies the mechanisms by which its overactivity contributes to the pathophysiology of this disease.

Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single-nucleotide polymorphism rs55705857, which confers a sixfold greater risk of isocitrate dehydrogenase ( IDH) –mutant low-grade glioma (LGG). We reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. Mutating the orthologous mouse rs55705857 locus accelerated tumor development in an Idh1 R132H -driven LGG mouse model from 472 to 172 days and increased penetrance from 30% to 75%. Our work reveals mechanisms of the heritable predisposition to lethal glioma in ~40% of LGG patients.