Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention: A meta-analysis of randomized controlled trials.

Background: Optical Coherence Tomography (OCT), a high-resolution imaging modality, guides stent implantation during percutaneous coronary intervention (PCI). However, OCT-guided PCI safety and efficacy data is limited. Methods: MEDLINE, Embase, and Cochrane Central were searched for randomized controlled trials (RCTs) comparing OCT-guided PCI to Angiography-guided PCI from inception to August 2023. A random-effects model was used to pool risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs) for clinical endpoints. Results: Our analysis included 5,139 patients from 11 studies. OCT-guided PCI resulted in a higher minimum stent area (MD = 0.35 [95 % CI, 0.21-0.49]; p < 0.00001), significantly reduced risk of cardiovascular mortality (RR = 0.56 [95 % CI, = 0.32-0.99]; p = 0.04), stent thrombosis (RR = 0.56 [95 % CI, 0.32-0.96]; p = 0.04), stent malapposition RR = 0.79 [95 % CI, 0.71-0.88]; p = < 0.0001) and major edge dissection (RR = 0.47 [95 % CI, 0.34-0.65]; p = <0.00001). However, no statistically significant difference was observed for all-cause mortality (RR = 0.71; p = 0.06), major adverse cardiovascular events (MACE) [RR = 0.80; p = 0.10], myocardial infarction (MI) [RR = 0.84; p = 0.16], target lesion revascularization (TLR) [RR = 0.94; p = 0.68], and target vessel revascularization (TVR) [RR = 0.91; p = 0.52]. Conclusion: OCT-guided PCI led to an increased MSA and decreased cardiovascular mortality, stent thrombosis, stent malapposition, and major edge dissection. The incidence of all-cause mortality, MACE, MI, TLR, and TVR remained comparable across the two groups.

Clinical Outcomes With Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Insulin-Naïve and Previously Insulin-Treated Individuals With Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials.

AIMS: The once-weekly insulin icodec, a new basal insulin analog, may positively support a reduction in injection frequency and improve adherence to therapy in type 2 diabetes (T2D). This study aimed to evaluate the safety and efficacy of insulin icodec compared with those of once-daily glargine U100. METHODS: A comprehensive literature search was conducted using PubMed/MEDLINE, Embase and the Cochrane Library from inception till September 2023. Data about clinical outcomes in both groups were extracted. Forest plots were generated using the random-effects model by pooling odds ratios (ORs) and mean differences (MDs). RESULTS: Five randomised controlled trials and 2019 individuals with T2DM were included. In the pooled analysis, time in range was significantly higher (MD = 4.35; 95% CI: 1.65 to 7.05; p = 0.002) in the icodec group than in the once-daily glargine group. The HbA1c levels were significantly reduced (MD = -0.13; 95% CI: -0.24 to -0.03; p = 0.02) in the weekly icodec group compared with those in the once-daily glargine group. The weight gain was significantly less in the glargine group than in the weekly icodec group (MD = 0.41; 95% CI: 0.04 to 0.78; p = 0.03); however, in the subgroup analysis, this change became statistically insignificant in both insulin-naïve and previously insulin-treated individuals. The results were comparable across two groups for fasting plasma glucose levels, hypoglycaemia alert (Level 1), clinically significant (Level 2) or severe hypoglycaemia (Level 3), and adverse events. CONCLUSION: Insulin icodec was associated with a reduction in glycated haemoglobin levels and higher time in range, with a similar safety profile as compared to insulin glargine U100. However, further evidence is still needed to reach a definitive conclusion.

Clinical Outcomes With Nurse-Coordinated Multidisciplinary Care in Patients With Heart Failure: A Systematic Review and Meta-analysis.

The American Heart Association (AHA) and the European Society of Cardiology (ESC) recommend nurse-inclusive multidisciplinary care for patients with heart failure (HF). However, there is no meta-analysis that focuses specifically on the impact of nurse-coordinated multidisciplinary care. Considering this literature gap, we conducted this review that seeks to systematically synthesize the current evidence available regarding the impact of nurse-coordinated multidisciplinary care on clinical outcomes in patients with HF. A comprehensive search was done using PubMed/Medline, Cochrane Library, and EMBASE from inception till July 2023 for randomized controlled trials (RCTs) comparing nurse-coordinated multidisciplinary care with usual care in adult patients (>18 years) with acute or chronic HF. Data about all-cause mortality, HF-related hospitalizations, and all-cause hospitalizations was extracted, pooled, and analyzed. Forrest plots were generated using the random effects model. A total of 30 RCTs were included in the analysis with a total of 7950 HF patients. Our pooled analysis demonstrated a significant reduction in all-cause mortality in HF patients who received nurse-coordinated multidisciplinary care (RR = 0.80, 95% CI: 0.72-0.88, P = 0.0001). Similarly, there was a significantly lesser risk of HF-related hospitalizations (RR = 0.56, 95% CI: 0.45-0.71, P = 0.00001) and all-cause hospitalizations (RR = 0.78, 95% CI: 0.70-0.87, P = 0.0001) among HF patients with nurse-coordinated multidisciplinary care as compared to the usual care. Nurse-coordinated multidisciplinary care significantly reduces the risk of all-cause mortality, HF-related hospitalizations, and all-cause hospitalizations in HF patients' posthospital discharge.

A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation.

SETD2-dependent H3 Lysine-36 trimethylation (H3K36me3) has been recently linked to the deposition of de-novo DNA methylation. SETD2 is frequently mutated in cancer, however, the functional impact of SETD2 loss and depletion on DNA methylation across cancer types and tumorigenesis is currently unknown. Here, we perform a pan-cancer analysis and show that both SETD2 mutation and reduced expression are associated with DNA methylation dysregulation across 21 out of the 24 cancer types tested. In renal cancer, these DNA methylation changes are associated with altered gene expression of oncogenes, tumour suppressors, and genes involved in neoplasm invasiveness, including TP53, FOXO1, and CDK4. This suggests a new role for SETD2 loss in tumorigenesis and cancer aggressiveness through DNA methylation dysregulation. Moreover, using a robust machine learning methodology, we develop and validate a 3-CpG methylation signature which is sufficient to predict SETD2 mutation status with high accuracy and correlates with patient prognosis.

Clinical Outcomes With Furosemide Versus Torsemide in Patients With Heart Failure: An Updated Systematic Review and Meta-Analysis.

Despite potential advantages of torsemide over furosemide, <10% of the patients with heart failure (HF) are on torsemide in clinical practice. Prior studies comparing furosemide to torsemide in patients with HF have shown conflicting findings, regarding hospitalizations and mortality. We aimed to pool all the studies conducted to date and provide the most updated and comprehensive evidence, regarding the effect of furosemide vs torsemide in reducing mortality and hospitalizations in patients with HF. We conducted a comprehensive literature search of the PubMed/Medline, Cochrane Library and Scopus from inception till June 2023, for randomized and nonrandomized studies comparing furosemide to torsemide in adult patients (>18 years) with acute or chronic HF. Data about all-cause mortality, HF-related hospitalizations and all-cause hospitalizations was extracted, pooled, and analyzed. Forest plots were created based on the random effects model. A total of 17 studies (n = 11,996 patients) were included in our analysis with a median follow-up time of 8 months. Our pooled analysis demonstrated no difference in all-cause mortality between furosemide and torsemide groups in HF patients (OR = 0.98, 95% CI: 0.75-1.29, P = 0.89). However, torsemide was associated with a significantly lesser incidence of HF-related hospitalizations (OR = 0.73, 95% CI: 0.54-0.99, P = 0.04), and all-cause hospitalizations (OR = 0.84, 95% CI: 0.73-0.98, P = 0.03), as compared to furosemide. Torsemide significantly reduces HF-related and all-cause hospitalizations as compared to furosemide, with no difference in mortality. We recommend transitioning from furosemide to torsemide in HF patients who are not attaining symptomatic control.

Structural and Functional Analysis of Pullulanase Type 1 (PulA) from Geobacillus thermopakistaniensis.

Pullulanase type I (PulA) is a debranching enzyme that specifically cleaves α-1,6-glycosidic linkages in pullulan. Pullulan has not only diverse applications in food industry but also has immune-stimulatory effects on B and T cells, and found to enhance the production of various anti-inflammatory cytokines in human. Moreover, pullulan has been suggested as a possible anti-cancer drug delivery agent without adjuvant due to its unique structure. The process of pullulan degradation is unresolved due to imprecise pullulanase structural characteristics. Therefore, the present study aimed to understand the structural and functional characteristics of pullulanase enzyme from Geobacillus thermopakistaniensis MAS1 strain using various computational approaches. The physio-chemical topographies and secondary structure of GT_PulA were explored using ProPram, InterPro and SMART. Various tools like I-TASSER, ModRefiner, RAMPAGE, PROCHECK and MOE 2009.10 were used to construct and verify the 3D structural model. The structural elucidation confirmed the significant domains, i.e., CBM48, CBM2, and TIM barrel having catalytically active residues, and conserved region YNGWDP. CBM2 domain along with TIM barrel has a capacity to bind different ligands and proved favorable for multiple substrate catalyses. These structural properties can have a potential effect on enhancing enzymatic activity of GT_PulA enzyme.