Clinical Utility of Intravascular Ultrasound (IVUS) in Carotid Artery Interventions: A Systematic Review and Meta-analysis.

BACKGROUND: Carotid plaque morphology plays an important role in determining outcome of carotid artery stenting (CAS). Intravascular ultrasound (IVUS) and its extension VH (Virtual Histology)-IVUS evaluate plaque characteristics in real time and guide decision making during stenting. To date, there is no consensus about indications of IVUS and its validated methods. This systematic review and meta-analysis aims to evaluate the clinical utility of IVUS in carotid artery interventions (CAS) and develop a future consensus for research and practice parameters. METHODS: A systematic review and meta-analysis was performed of the English literature articles published till February 2021. Studies reporting on IVUS parameters and findings and also its performance compared with other imaging modalities were included in review. Pooled prevalence with 95% confidence intervals (CI) was calculated. The statistical analysis was conducted in R version 3.6.2. RESULTS: A total of 2015 patients from 29 studies were included. Proportional meta-analysis was performed on 1566 patients from 11 studies. In 9 studies, stroke/transient ischemic attack (TIA) had a pooled prevalence of 4% (95% CI 3%-5%) while asymptomatic stroke had a pooled prevalence of 46% (95% CI 31%-62%) in 4 studies following IVUS. Two studies reported that IVUS detected more plaque protrusion compared with angiography (n=33/396 vs 11/396). IVUS led to stent type or size change in 8 of 48 cases which were missed on angiography in 3 other studies. Concordance between VH-IVUS and true histology was good at 80% to 85% reported in 2 studies. CONCLUSIONS: This systematic review and meta-analysis showed, though IVUS fared better to computed tomography (CT)/magnetic resonance (MR) angiography for better stent selection during CAS, with low to moderate risk of bias in the studies included. However, large scale, preferably randomized controlled studies are needed to predict its role in determining clinical outcome.

Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review.

Bone marrow mononuclear cell (BM-MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM-MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM-MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta-analysis. We included non-randomized open-label, single-arm and non-randomized comparative studies or randomized controlled trials (RCTs) if BM-MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non-randomized comparative trials and four single-arm open-label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta-analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score ≤2) in six studies involving 122 subjects was 29% (95% CI 0.16-0.43) who were exposed to BM-MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM-MNCs was 20% (95% CI 0.12-0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM-MNC therapy is safe up to 1 year post-intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well-designed randomized controlled trials are required to provide more information on the efficacy of BM-MNC transplantation in patients with IS.

High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis.

Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings.

Association between beta-1 adrenergic receptor gene polymorphism and ischemic stroke in North Indian population: a case control study.

Stroke is a multi-factorial disease caused by a combination of genetic and environmental factors. The purpose of this case control study was to determine the relationship of beta-1 adrenergic receptor polymorphism with ischemic stroke in North Indian population. In this study, 224 patients and 224 age- and sex-matched controls were recruited from the outpatient department and neurology ward of All India Institute of Medical Sciences, New Delhi. Genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. PCR results were confirmed by DNA sequencing. Frequency distributions of genotypes and alleles were compared between cases and controls using logistic regression. Mean age of cases and controls was 53.9 ± 13.4 and 53.6 ± 12.9 years respectively. Multivariate logistic regression analysis showed an independent association between Ser49Gly polymorphism and ischemic stroke under a dominant model of inheritance (OR, 2.5; 95% CI, 1.2 to 5) and large vessel disease (LVD) under a recessive model of inheritance (OR, 6.5; 95% CI, 1.7 to 23; P=0.005). Independent association of Arg389Gly polymorphism with small vessel disease (SVD) (OR, 7.09; 95% CI, 1.9 to 25; P=0.003) under recessive model of inheritance. The findings of the present study Ser49Gly polymorphism of the ADRB1 gene confer higher risk of ischemic stroke in a North Indian population and especially in patients with LVD. Our findings also show that Arg389Gly polymorphism of ADRB1 confers higher risk of SVD in North Indian population.

Macro invertebrate community from Sonamarg streams of Kashmir Himalaya.

This study analyses a macroinvertebrate community survey for River Sindh and its tributary including Baltal, Yashmarg, Sonamarg and Thajwas Grar considering the extreme hydrological conditions linked with the seasonal low-flow period typical for some streams in this area. This study attempts to provide an overview of the macro invertebrate assemblages and physico-chemical variables of the River Sindh and its important tributary. Four study sites were selected from the River Sindh and its tributary including Baltal, Yashmarg, Sonamarg and Thajwas Grar for studying the ecological distribution of Macroinvertebrate assemblages. Totally, 33 taxa of macroinvertebrates were recorded from the two streams belonging to Mollusca-3 (Gastropoda-2 and Bivalvia-1), Annelida-1 and Arthropoda-29 (Insecta-29). Among insects Ephemeroptera (7), Trichoptera (6) and Diptera (13) dominated. Except Yashmrag all sites were found devoid of annelids while as the mollusks were found absent at Sonamarg. Highest values of Shannon Weiner Index were found at Yashmarg (2.42) and lowest at Sonamarg (1.99) while as highest and lowest Sorensen's similarity coefficient were found between Baltal/Thajwas Grar (0.68) and Yashmarg/Thajwas Grar (0.39), respectively. A perusal of the data on physico-chemical characteristics showed that these streams were hard water type with high dissolved oxygen content. The ionic composition of the stream waters revealed the predominance of bicarbonate and calcium. Insecta dominated both qualitatively as well as quantitatively and the study revealed that the substrate compositions dominated by gravel, pebble and leaf litters are primary determinants of the invertebrate community structure recording maximum species diversity and abundance. Sample locations impacted by Amarnath yatris pilgrimage comparatively reflected slightly higher increase in nutrients than Thajwas Grar almost devoid of pilgrimage effect.

Acute pancreatitis: rare complication of chicken pox in an immunocompetent host.

Chicken pox is a highly contagious infection, caused by the varicella zoster virus. Although generally a benign, self-limited disease, varicella may be associated with serious complications especially in adults. We present acute pancreatitis- a rare complication, in otherwise healthy patients suffering from chicken pox. The presence of pancreatitis in association with chickenpox in immunocompetent patients can influence the outcome of the latter. This interesting case will hopefully increase awareness about this complication and its fatality in chicken pox.

mDYRK3 kinase is expressed selectively in late erythroid progenitor cells and attenuates colony-forming unit-erythroid development.

DYRKs are a new subfamily of dual-specificity kinases that was originally discovered on the basis of homology to Yak1, an inhibitor of cell cycle progression in yeast. At present, mDYRK-3 and mDYRK-2 have been cloned, and mDYRK-3 has been characterized with respect to kinase activity, expression among tissues and hematopoietic cells, and possible function during erythropoiesis. In sequence, mDYRK-3 diverges markedly in noncatalytic domains from mDYRK-2 and mDYRK-1a, but is 91.3% identical overall to hDYRK-3. Catalytically, mDYRK-3 readily phosphorylated myelin basic protein (but not histone 2B) and also appeared to autophosphorylate in vitro. Expression of mDYRK-1a, mDYRK-2, and mDYRK-3 was high in testes, but unlike mDYRK1a and mDYRK 2, mDYRK-3 was not expressed at appreciable levels in other tissues examined. Among hematopoietic cells, however, mDYRK-3 expression was selectively elevated in erythroid cell lines and primary pro-erythroid cells. In developmentally synchronized erythroid progenitor cells, expression peaked sharply following exposure to erythropoietin plus stem cell factor (SCF) (but not SCF alone), and in situ hybridizations of sectioned embryos revealed selective expression of mDYRK-3 in fetal liver. Interestingly, antisense oligonucleotides to mDYRK-3 were shown to significantly and specifically enhance colony-forming unit-erythroid colony formation. Thus, it is proposed that mDYRK-3 kinase functions as a lineage-restricted, stage-specific suppressor of red cell development. (Blood. 2001;97:901-910)

Signal transduction in the erythropoietin receptor system.

Events relayed via the single transmembrane receptor for erythropoietin (Epo) are essential for the development of committed erythroid progenitor cells beyond the colony-forming unit-erythroid stage, and this clearly involves Epo's inhibition of programmed cell death (PCD). Less well resolved, however, are issues regarding the precise nature of Epo-dependent antiapoptotic mechanisms, the extent to which Epo might also promote mitogenesis and/or terminal erythroid differentiation, and the essential vs modulatory nature of certain Epo receptor cytoplasmic subdomains, signal transducing factors, and downstream pathways. Accordingly, this review focuses on the following aspects of Epo signal transduction: (1) Epo receptor/Jak2 activation mechanisms; (2) the critical vs dispensable nature of (P)Y sites and SH2 domain-encoding effectors in survival, growth, and differentiation responses; (3) primary mechanisms by which Epo inhibits PCD; (4) the integration of signals relayed by coexpressed and possibly directly interacting cytokine receptors; and (5) predictions regarding effector function which are provided by the association of certain primary and familial polycythemias with mutated human Epo receptor forms.