Low triiodothyronine (T3) levels predict worse outcomes in autoimmune encephalitis-A meta-analysis of current literature.

INTRODUCTION: An unusual association between thyroid dysfunction and autoimmune encephalitis (AE) was noticed when patients presented with low free triiodothyronine (fT3) levels and antithyroid antibodies. We conducted a meta-analysis to investigate whether thyroid dysfunction, that is, lower fT3 levels are associated with worsening clinical manifestations and prognosis in patients with AE. METHODS: Literature search of five electronic databases was performed till April 5, 2023. Inclusion criteria were as follows: Observational studies reporting patients with all subtypes of AE and assessing thyroid dysfunction categorized as low fT3 and non-low fT3. Primary endpoints included modified Rankin scale (mRS) at admission, abnormal magnetic resonance imaging, length of stay, seizures, and consciousness declination. RESULTS: Comprehensive literature search resulted in 5127 studies. After duplicate removal and full-text screening, six observational studies were included in this analysis. Patients with low fT3 were 2.95 times more likely to experience consciousness declination (p = .0003), had higher mRS at admission (p < .00001), had 3.14 times increased chances of having a tumor (p = .003), were 3.88 times more likely to experience central hypoventilation, and were 2.36 times more likely to have positivity for antithyroid antibodies (p = .009) as compared to patients with non-low fT3. CONCLUSION: The findings of our study suggest that low fT3 levels might be related to a more severe disease state, implying the significance of thyroid hormones in AE pathogenesis. This finding is crucial in not only improving the early diagnosis of severe AE but also in the efficient management of the disease.

Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace. METHODS: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes. RESULTS: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo. CONCLUSION: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Transcatheter Edge-to-Edge Repair for Tricuspid Regurgitation-A Systematic Review and Meta-Analysis.

Transcatheter edge-to-edge repair (TEER) has emerged as a widely accepted procedure for tricuspid regurgitation (TR) as gauged by echocardiographic parameters and clinical outcomes. Our study aims to assess TR severity and other echocardiographic outcomes in patients undergoing TEER with TriClip, MitraClip, and PASCAL devices. A literature search of 5 databases was performed until 1st June 2023. Randomized controlled trials (RCTs) or observational studies with moderate to severe (grade III-V) TR patients undergoing isolated TEER were considered eligible. Echocardiographic, and quality of life determining outcomes such as improvement in TR severity grade ≥3, New York Heart Association (NYHA) class ≥3, procedural success, 6-minute walking distance (6MWD), and adverse outcomes were analyzed. Grade assessment was performed and studies were assessed for risk of bias and publication bias. We included 15 studies (14 observational and 1 RCT) in our paper. Analysis revealed a substantial reduction in TR volume (P < 0.00001), TR grading (P < 0.00001), tricuspid annular diameter (P < 0.00001), proximal isovelocity surface area radius (P < 0.00001), effective regurgitant orifice area (P < 0.00001), and improvement in NYHA class (P < 0.00001) at 30 days from baseline, postprocedurally. A significant increase in 6MWD at 1 year (P = 0.001) was also recorded. No significant differences in left ventricular ejection fraction (P = 0.87), fractional area change (P = 0.37), or tricuspid annular plane systolic excursion (P = 0.76) were observed. TEER procedural success was 97%. TEER produced a significant reduction in TR grade and volume, NYHA class, 6MWD, and showed prominent procedural success. Large scale RCTs comparing the TEER devices are needed to strengthen the present findings.

Valve-in-valve transcatheter mitral valve replacement versus redo-surgical mitral valve replacement for degenerated bioprosthetic mitral valves: A systematic review and meta-analysis.

Bioprosthetic mitral valve degeneration is traditionally treated with Redo-SMVR, but the latest ViV-TMVR procedure offers a less invasive and lower risk alternative. A systematic literature search was conducted on Cochrane Central, Scopus, and Medline (PubMed interface) electronic databases from inception till 15th April 2024. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes. We included a total of eleven studies with 11,931 patients in the final quantitative and qualitative analysis. When comparing ViV-TMVR with Redo-SMVR, no significant difference was found for 30-day mortality (P = 0.13) and 1-year mortality (P = 0.91), whereas patients in the ViV-TMVR showed significantly reduced incidence of stroke (P < 0.00001), In-hospital mortality (P), bleeding complications (P = 0.003), AKI (P = 0.0006), arrhythmias (P = 0.01), LVOT obstruction (P = 0.04), and PPI (P < 0.00001). Furthermore, no significant difference was observed between either group when comparing vascular complications (P = 0.97), 2-year mortality (P = 0.60) and 3-year mortality. ViV-TMVR was associated with a significant risk of paravalvular leakage (P = 0.008). Although, ViV-TMVR reduces the risk of complications associated with Redo-SMVR, larger studies are imperative to reach conclusive results.

Valve-in-Valve Transcatheter Aortic Valve Replacement Versus Redo-Surgical Aortic Valve Replacement in Patients With Aortic Stenosis: A Systematic Review and Meta-analysis.

Aortic stenosis is a common and significant valve condition requiring bioprosthetic heart valves with transcatheter aortic valve replacement (TAVR) being strongly recommended for high-risk patients or patients over 75 years. This meta-analysis aimed to pool existing data on postprocedural clinical as well as echocardiographic outcomes comparing valve-in-valve (ViV)-TAVR to redo-surgical aortic valve replacement to assess the short-term and medium-term outcomes for both treatment methods. A systematic literature search on Cochrane Central, Scopus, and Medline (PubMed interface) electronic databases from inception to August 2023. We used odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Twenty-four studies (25,216 patients) were pooled with a mean follow-up of 16.4 months. The analysis revealed that ViV-TAVR group showed a significant reduction in 30-day mortality (OR 0.50, 95% confidence interval [CI] 0.43 to 0.58, p <0.00001), new-onset atrial fibrillation (OR 0.34, 95% CI 0.17 to 0.67, p = 0.002), major bleeding event (OR 0.28, 95% CI 0.17 to 0.45, p <0.00001) and lower rate of device success (OR 0.25, 95% CI 0.12 to 0.53, p = 0.0003). There were no significant differences between either group when assessing 1-year mortality, stroke, myocardial infarction, postoperative left ventricular ejection fraction, and effective orifice area. ViV-TAVR cohort showed a significantly increased incidence of paravalvular leaks, aortic regurgitation, and increased mean aortic valve gradient. ViV-TAVR is a viable short-term option for older patients with high co-morbidities and operative risks, reducing perioperative complications and improving 30-day mortality with no significant cardiovascular adverse events. However, both treatment methods present similar results on short-term to medium-term complications assessment.

Genome-wide identification of NAC transcription factors and regulation of monoterpenoid indole alkaloid biosynthesis in Catharanthus roseus.

NAC transcription factors (TFs) are crucial to growth and defense responses in plants. Though NACs have been characterized for their role in several plants, comprehensive information regarding their role in Catharanthus roseus, a perennial ornamental plant, is lacking. Homology modelling was employed to identify and characterize NACs in C. roseus. In-vitro propagation of C. roseus plants was carried out using cell suspension and nodal culture and were elicited with two auxin-antagonists, 5-fluoro Indole Acetic Acid (5-F-IAA) and α-(phenyl ethyl-2-oxo)-Indole-Acetic-Acid (PEO-IAA) for the enhanced production of monoterpenoid indole alkaloids (MIAs) namely catharanthine, vindoline, and vinblastine. Analyses revealed the presence of 47 putative CrNAC genes in the C. roseus genome, primarily localized in the nucleus. Phylogenetic analysis categorized these CrNACs into eight clusters, demonstrating the highest synteny with corresponding genes in Camptotheca acuminata. Additionally, at least one defense or hormone-responsive cis-acting element was identified in the promoter region of all the putative CrNACs. Of the two elicitors, 5-F-IAA was effective at 200 µM to elicit a 3.07-fold increase in catharanthine, 2.76-fold in vindoline, and 2.4-fold in vinblastine production in nodal culture. While a relatively lower increase in MIAs was recorded in suspension culture. Validation of RNA-Seq by qRT-PCR showed upregulated expression of stress-related genes (CrNAC-07 and CrNAC-24), and downregulated expression of growth-related gene (CrNAC-25) in elicited nodal culture of C. roseus. Additionally, the expression of genes involved in the biosynthesis of MIAs was significantly upregulated upon elicitation. The current study provides the first report on the role of CrNACs in regulating the biosynthesis of MIAs.

Effect of methoxyverapamil, diltiazem, morphine and their combination on the formation of irreversibly sickled cells: an in vitro study

The effect of methoxyverapamil and diltiazem [calcium antagonists] and morphine [calcium antagonist activity] on the formation of irreversibly sickled cells [ISCs] was investigated. Methoxyverapamil at therapeutic concentration and 10 times that level resulted in a 12% and 21% reduction in the formation of ISCs respectively, which was statistically significant. Diltiazem also produced a significant reduction in ISCs but morphine produced no significant reduction. Combination of these drugs produced a net effect similar to their individual effects. These drugs might be useful in decreasing the intensity of sickling crises and vaso-occlusive events. Thus in vivo trials in patients with sickle-cell disease are suggested