Expanding the phenotypic and genotypic spectrum of DYT-TUBB4A with seven patients from India.

BACKGROUND: Variants in the TUBB4A gene are associated with dystonia (DYT-TUBB4A), Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC) and spastic paraplegia. Phenotypes intermediate to these three broad phenotypes are also observed. These are rare disorders, and data from diverse populations remains limited. We report seven Indian cases with dystonia phenotype related to TUBB4A mutation. CASES: Among these seven patients, age at onset ranged from 5 to 48 years. Five patients had cranio-cervical onset of dystonia. One patient had prominent parkinsonism with dystonia. Patients responded well to botulinum toxin injected for laryngeal, cervical and jaw dystonia. The patient with parkinsonism responded well to levodopa, albeit with development of dyskinesias. Apart from the common p.Arg2Gly variant in three patients with DYT-TUBB4A, other variants included p.Arg262Pro, p.Arg39Cys and p.Asp245Asn. CONCLUSIONS: We report the first collection of cases with TUBB4A mutation from India. We expand the phenotype to include levodopa-responsive parkinsonism. Indian patients, consistent with global literature, harbor prominent adductor dysphonia, cervical and jaw dystonia, which responds well to botulinum treatment.

Acute bilateral sensorineural hearing loss as presentation of leptomeningeal metastases.

We describe a rare occurrence of bilateral acute severe sensorineural hearing loss in a middle-aged man that heralded the diagnosis of metastatic gastric cancer.

Effectiveness of Yoga in Modulating Markers of Immunity and Inflammation: A Systematic Review and Meta-Analysis.

Chronic inflammation is central to the pathogenesis of many chronic inflammatory conditions. This review aims to analyze whether the practice of yoga, or yogic meditation and breathing, has any effect on the levels of inflammatory cytokines and other inflammatory markers in patients with various chronic inflammatory diseases such as rheumatoid arthritis, neoplastic disorders, and asthma, as well as in healthy subjects, compared to usual care or sham interventions. A comprehensive search of databases (PubMed, CENTRAL, Embase, and CINAHL) was performed. Randomized controlled trials (RCTs) that evaluated the effects of yoga as an intervention on inflammatory markers were analyzed. A total of 26 studies were included. Only two studies had a low risk of bias (RoB); 24 other studies had a high RoB. Most studies (n=24) reported a favorable outcome with yoga, irrespective of the type of yoga used, the condition studied, and the duration of the intervention. The commonly reported inflammatory markers included IL-6 (n=17), tumor necrosis factor-alpha (TNF-a) (n=13), and C-reactive protein (CRP) (n=10). Most studies showed a significant reduction in inflammatory markers in the yoga group (YG) compared to the control group (CG). Few studies also showed significant improvement in markers of cellular immunity (interferon gamma (IFN-g), IL-10, and transforming growth factor-beta (TGF-b); n=2 each) and improved mucosal defense (IgA, IL-6, and IL-2; n=2 each). A meta-analysis of IL-6, TNF-a, and CRP showed yoga had a favorable effect on the levels of these markers, but it was not statistically significant. Current evidence suggests that yoga can be a complementary intervention for various chronic inflammatory conditions. However, the quality of the evidence is poor, along with considerable heterogeneity. In the future, investigators should describe the intervention better, with a uniform assortment of outcome measures and treatment conditions, to generate high-quality evidence.

Definitions, etiologies and outcomes of acute on chronic liver failure: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a major public health concern. We aimed to assess the definitions, etiological spectrum, organ failure (OF), and outcomes of ACLF globally. METHODS: Three databases were searched for studies on ACLF from 1990 till September 2022. Information regarding definitions, acute precipitants, underlying chronic liver disease (CLD), OF, and mortality were extracted. Meta-analyses were performed for pooled prevalence rates (95% confidence interval, CI) using random effects model for each definition of ACLF. RESULTS: Of the 11,451 studies identified, 114 articles (142 cohorts encompassing 210,239 patients) met the eligibility criteria. Most studies (53.2%) used the European Association for the Study of the Liver (EASL) definition, followed by Asia-Pacific Association for the Study of the Liver (APASL) (33.3%). Systemic infection was the major acute precipitant and alcohol use was the major cause of CLD in EASL-defined studies while alcohol was both, the major acute precipitant and cause of CLD in APASL-defined studies. Liver failure was the major OF in APASL-based studies, while renal failure was predominant in EASL-based studies. Thirty-day mortality varied across definitions: APASL: 38.9% [95%CI 31.2-46.9], EASL: 47.9% [95%CI 42.2-53.5] and NACSELD: 52.2% [95%CI 51.9-52.5]. Diagnostic overlap between definitions ranged from 7.7% to 80.2%. Meta-regression suggested that the WHO region influenced 30-day mortality in studies using EASL definition. CONCLUSION: Heterogeneity in the definition of ACLF proposed by different expert societies and regional preferences in its use result in differences in clinical phenotype and outcomes. A uniform definition would enhance the comparability and interpretation of global data.

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome.

BACKGROUND: There is scant literature on hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS). AIM: To assess the magnitude, clinical characteristics, feasibility, and outcomes of treatment in BCS-HCC. METHODS: A total of 904 BCS patients from New Delhi, India and 1140 from Mumbai, India were included. The prevalence and incidence of HCC were determined, and among patients with BCS-HCC, the viability and outcomes of interventional therapy were evaluated. RESULTS: In the New Delhi cohort of 35 BCS-HCC patients, 18 had HCC at index presentation (prevalence 1.99%), and 17 developed HCC over a follow-up of 4601 person-years, [incidence 0.36 (0.22-0.57) per 100 person-years]. BCS-HCC patients were older when compared to patients with BCS alone (P = 0.001) and had a higher proportion of inferior vena cava block, cirrhosis, and long-segment vascular obstruction. The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up (13029 ng/mL vs 500 ng/mL, P = 0.01). Of the 35 BCS-HCC, 26 (74.3%) underwent radiological interventions for BCS, and 22 (62.8%) patients underwent treatment for HCC [transarterial chemoembolization in 18 (81.8%), oral tyrosine kinase inhibitor in 3 (13.6%), and transarterial radioembolization in 1 (4.5%)]. The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo (P = 0.0001). In contrast to the New Delhi cohort, the Mumbai cohort of BCS-HCC patients were predominantly males, presented with a more advanced HCC [Barcelona Clinic Liver Cancer C and D], and 2 patients underwent liver transplantation. CONCLUSION: HCC is not uncommon in patients with BCS. Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

Knowledge and Skills in Cardiopulmonary Resuscitation and Effect of Simulation Training on it among Healthcare Workers in a Tertiary Care Center in India.

Aim and background: High-quality cardiopulmonary resuscitation (CPR) is associated with improved patient outcomes, but healthcare workers (HCWs) may be frequently undertrained. This study aimed to assess baseline knowledge and skills among HCWs about basic and advanced life support and the effect of simulation-based training on it. Methods: It was a single-center prospective quasi-interventional study among resident doctors and nurses at a Tertiary Center in New Delhi, India. A questionnaire-based assessment was done to assess baseline knowledge. The participants then underwent simulation-based training followed by questionnaire-based knowledge assessment and skill assessment. A repeat questionnaire-based assessment was done 6 months post-training to assess knowledge retention. Results: A total of 82 HCWs (54 doctors and 28 nurses) were enrolled. The participants scored 22.28 ± 6.06 out of 35 (63.65%) in the pre-training knowledge assessment, with low scores in post-cardiac arrest care, advanced life support, and defibrillation. After the training, there was a significant rise in scores to 28.32 ± 4.08 out of 35 (80.9%) (p < 0.01). The retention of knowledge at 6 months was 68.87% (p < 0.01). The participants scored 92.61 ± 4.75% marks in skill assessment with lower scores in chest compressions and team leadership roles. There was a positive correlation (r = 0.35) between knowledge and skills scores (p < 0.01). Conclusion: There is a progressive decrease in baseline knowledge of HCWs with the further steps in the adult chain of survival. The simulation training program had a positive impact on the knowledge of HCWs. The training programs should focus on defibrillation, advanced life support, post-cardiac arrest care, and leadership roles. How to cite this article: Agarwal A, Baitha U, Ranjan P, Swarnkar NK, Singh GP, Baidya DK, et al. Knowledge and Skills in Cardiopulmonary Resuscitation and Effect of Simulation Training on it among Healthcare Workers in a Tertiary Care Center in India. Indian J Crit Care Med 2024;28(4):336-342.

Bridging the gap between statistical significance and clinical relevance: A systematic review of minimum clinically important difference (MCID) thresholds of scales reported in movement disorders research.

Background: Minimum clinically important difference (MCID) is the smallest change in an outcome measure that is considered clinically meaningful. Using validated MCID thresholds for outcomes powers trials adequately to detect meaningful treatment effects, aids in their interpretation and guides development of new outcome measures. Objectives: To provide a comprehensive summary of MCID thresholds of various symptom severity scales reported in movement disorder. Methods: We conducted systematic review of the literature and included studies of one or more movement disorders, and reporting MCID scales. Results: 2763 reports were screened. Final review included 32 studies. Risk of bias (RoB) assessment showed most studies were of good quality. Most commonly evaluated scale was Unified Parkinson's Disease Rating Scale (UPDRS) (11 out of 32). Four studies assessing MDS-UPDRS had assessed its different sub-parts, reporting a change of 2.64,3.05,3.25 and 0.9 points to detect clinically meaningful improvement and 2.45,2.51,4.63 and 0.8 points to detect clinically meaningful worsening, for the Part I, II, III and IV, respectively. For Parts II + III, I + II + III and I + II + III + IV, MCID thresholds reported for clinically meaningful improvement were 5.73, 4.9, 6.7 and 7.1 points respectively; while those for clinically meaningful worsening were 4.7, 4.2, 5.2 and 6.3 points, respectively. MCID thresholds reported for other scales included Abnormal Involuntary Movement Scale (AIMS), Toronto Western Spasmodic Torticollis Rating Scale (TWSRS), and Burke-Fahn-Marsden Dystonia Scale (BFMD). Conclusion: This review summarizes all the MCID thresholds currently reported in Movement disorders research and provides a comprehensive resource for future trials, highlighting the need for standardized and validated MCID scales in movement disorder research.

The Pitfalls of NIHSS: Time for a New Clinical Acute Stroke Severity Scoring System in the Emergency?

Stroke is the second leading cause of death and a major cause of disability worldwide. Stroke severity scales serve as reliable means to track a patient's neurological deficit, predict outcome, and guide treatment decisions in clinical practice. The National Institute of Health Stroke Scale (NIHSS) was introduced over 30 years ago, marking a significant milestone in the field of stroke. Over the years, there have been notable advancements in acute stroke care. Despite several modifications made to NIHSS, none has yet succeeded in effectively capturing all the complex effects of a stroke. This review focuses on the pitfalls of NIHSS and emphasizes the need for a quick and comprehensive clinical and upgraded version of the stroke severity rating scale.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Minimal Clinically Important Difference of Scales Reported in Stroke Trials: A Review.

There is a growing awareness of the significance of using minimum clinically important differences (MCIDs) in stroke research. An MCID is the smallest change in an outcome measure that is considered clinically meaningful. This review is the first to provide a comprehensive summary of various scales and patient-reported outcome measures (PROMs) used in stroke research and their MCID values reported in the literature, including a concise overview of the concept of and methods for determining MCIDs in stroke research. Despite the controversies and limitations surrounding the estimation of MCIDs, their importance in modern clinical trials cannot be overstated. Anchor-based and distribution-based methods are recommended for estimating MCIDs, with patient self-evaluation being a crucial component in capturing the patient's perspective on their health. A combination of methods can provide a more comprehensive understanding of the clinical relevance of treatment effects, and incorporating the patient's perspective can enhance the care of stroke patients.