Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). METHODS: All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. RESULTS: Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. CONCLUSION: TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.

Transpyloric Feed in Reflux-Associated Apnea in Preterm Newborns: A Prospective Study.

Background: The etiological correlation between gastroesophageal reflux (GER) and apnea is controversial. We conducted a prospective interventional study designed to address the controversy. Methods: Preterm neonates with apnea at a tertiary care center, who had clinical features of GER without any other comorbidities likely to cause apnea, were included in the study. The enrolled neonates underwent continuous transpyloric tube feeding for 72 hours. The primary outcome measure was the difference in the number of apneic episodes pre- and post-initiation of nasoduodenal (ND) feeding. Secondary outcome measures included the incidence of necrotizing enterocolitis, other gastrointestinal disturbances, and mortality. Results: Sixteen preterm neonates were included in the study. A substantial proportion (n =11, 68.8%) of the included neonates had a reduction in the number of apneic episodes. There was a significant decrease in the mean number of apneic episodes from 1.75 (±0.837) to 0.969 (±0.957) (P=.007). The median number of apneas was 1.5 (IQR 0.875) before and 0.5 (IQR 0.875) after ND feeds. There were no serious adverse events observed that were attributable to transpyloric feeding. Conclusion: This prospective study suggests that in a selected group of preterm neonates with reflux- associated apnea, transpyloric feeding can be an effective therapeutic modality.

Congenital myasthenic syndrome: a tale of two siblings.

Congenital myasthenic syndromes are a group of rare neuromuscular junction disorders. Traditional anticholinesterase inhibitors may not help in congenital myasthenic syndromes and in some variants may actually cause deterioration of symptoms. In this report, we describe a rare case of congenital myasthenic syndrome with heterozygous mutations in CHRNE gene (c.128A > T; heterozygous; exon 11) and COLQ gene (c.1201T > A; heterozygous; exon 16), which did not show improvement on neostigmine test but responded to treatment with oral salbutamol.

Charcot-Marie-Tooth disease type 4J with spastic quadriplegia, epilepsy and global developmental delay: a tale of three siblings.

Charcot-Marie-Tooth (CMT) disease is mainly a disease of peripheral nervous system and patients typically present with features of demyelinating neuropathy or axonal neuropathy or both. Rarely patients present with features of central nervous system involvement. Parkinsonism, aphemia and familial epilepsy syndrome have previously come up as case reports in association with CMT type 4 J.We hereby describe a family with 3 siblings affected with CMT4J with homozygous FIG4 mutation who presented with global developmental delay, epilepsy and spastic quadriparesis.

Correlation of ATP7B gene mutations with clinical phenotype and radiological features in Indian Wilson disease patients.

INTRODUCTION: Wilson disease (WD) is characterized by a wide variety of clinical manifestations. Our study aimed to correlate genotype with clinical and radiological features in Indian WD patients. METHODS: We conducted a descriptive observational study in a tertiary care neurology referral center of eastern India over a period of 2 years. Demographic data collection, clinical examination and relevant investigations were done for all WD patients meeting the inclusion criteria. Based on previous reports of mutation hotspots for WD in Eastern India, we performed PCR-Sanger sequencing of selected exons of ATP7B gene. To understand the role of each of these covariates on the occurrence of common mutation, we applied a logistic regression as well as random forest in a supervised learning framework. RESULTS: Fifty-two WD patients were included in the study. c.813C > A (p.C271X) was the commonest identified mutation. The statistical methods applied to our data-set reveal the most important features for predicting common mutation or its absence. We also found that the state-of-the-art classification algorithms are good at predicting the absence of common mutation (with true positive rates being 0.7647 and 0.8823 for logistic classifier and random forest, respectively), but predicting the occurrence remains a harder modeling challenge. CONCLUSIONS: WD patients in eastern India have significant genotypic and phenotypic diversity. Statistical methods for binary classification show some early promise of detecting common mutations and suggest important covariates, but further studies with larger samples and screening of remaining exons are warranted for understanding the full genetic landscape of Wilson disease.

Spectrum of anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases: an Indian perspective.

Myelin oligodendrocyte glycoprotein antibody (MOG-Ab) is involved in the pathogenesis of central nervous system (CNS) demyelination disorders. We aimed to explore the spectrum of MOG-Ab-associated diseases in eastern India. A single-center, prospective observational study was done over a period of 2 years in a tertiary care hospital of eastern India. Patients with CNS demyelination disorders who tested positive for MOG-Ab using live cell-based assay were included in the study; while, those with age less than 1 year, documented preexisting CNS structural lesions, developmental delays or diagnosed multiple sclerosis were excluded. Demographic profile, clinical spectrum, disease course, radiological features as well as response to treatment were analyzed among included patients. Twenty MOG-Ab-positive patients were included (M:F 1:1.85). The median age of symptom onset was 10.5 years. The median follow-up of patients was 13 months. Acute disseminated encephalomyelitis (ADEM) was the commonest presentation at first attack (55%), followed by optic neuritis (ON) (45%). Patients with ADEM had a significantly lower age at first attack (p = 0.025). Monophasic and relapsing disease courses were seen in 45% and 55% patients, respectively. While all patients with only ADEM had a monophasic course, 77.8% with ON had a relapsing course. Among patients who presented with isolated transverse myelitis, 75% had a monophasic course and all had disease confined to the spinal cord. Good response to corticosteroids was seen in majority of participants. Second-line drugs were needed in 55% patients, rituximab being the commonest second-line agent used. 35% patients had significant disability (EDSS > 4) at last follow-up. MOG-Ab-associated diseases have diverse clinical phenotypes characterized by age-dependent pattern-specific courses.

Hotspots of H1N1 influenza in India: analysis of reported cases and deaths (2010-2017).

Influenza A (H1N1) caused significant mortality and morbidity globally. We identified the hotspots for H1N1 influenza in India using cases and deaths reported in the Integrated Disease Surveillance Program between 2010 and 2017. A total of 114,667 cases and 8543 deaths were reported from across India, at an overall case fatality rate of 7.5%. While Maharashtra accounted for 21% of cases and 31% of deaths, Delhi and Gujarat were ranked the highest based on the population-adjusted ranks for morbidity and mortality, respectively. The current analysis identified states and union territories in western India (Delhi, Punjab, Rajasthan, Gujarat and Maharashtra) to be especially vulnerable.

Musculoskeletal manifestations in pediatric patients infected with human immunodeficiency virus: Developing country perspective.

OBJECTIVE: Musculoskeletal manifestations in children infected with human immunodeficiency virus (HIV) are responsible for increased morbidity and decreased quality of life. Even in this era of highly active anti-retroviral therapy (HAART), there are limited studies on different rheumatological manifestations in pediatric patients with HIV, and the spectrum of musculoskeletal manifestation in pediatric HIV is yet to be established. METHODS: A single-center, prospective, observational study was carried out from October 2014 to September 2016 in a tertiary care hospital of Eastern India with 517 children infected with HIV aged between 3 and 19 years. Particulars of musculoskeletal involvement were at first screened with pediatric gait, arm, leg, spine (pGALS) screening protocol, followed by detailed examination in patients identified through screening. All the participants were re-examined at three and six months of follow-up. RESULTS: Musculoskeletal manifestations were found in 11.2% of the study population. The most common non-infective manifestation found in the study population was arthralgia (5.22%), followed by myalgia (3.29%). The prevalence of definite arthritis was found to be 6/1000 children, whereas infective manifestations (including arthritis, myositis, and osteomyelitis) were found in 2.12% of study population. Musculoskeletal manifestations were commonly found in children infected with HIV who were on anti-retroviral drugs. These manifestations were found commonly in the children in the second decade of their lives. Malnutrition, advanced stage of HIV infection (WHO clinical stage 4), lower CD4 count at the time of evaluation, and longer duration of disease were associated with increased frequency of musculoskeletal manifestations. CONCLUSION: Musculoskeletal manifestations are frequent in pediatric population infected with HIV. But for better delineation, further multicentric studies are warranted in future in children infected with HIV.

Neurological manifestations in children with dengue fever: an Indian perspective.

Ours was a descriptive observational cross-sectional study carried out in a tertiary care hospital in eastern India over a period of one year to study the profile of neurological involvement in paediatric dengue patients. Of 71 laboratory-confirmed cases, 20 (28.17%) had neurological involvement. Common forms observed were acute encephalopathy (40%), encephalitis (30%), pure motor weakness (15%), transverse myelitis (5%), acute disseminated encephalomyelitis (5%) and Guillain-Barré syndrome (5%). The dengue IgM antibody could be detected in the cerebrospinal fluid of only two patients with encephalitis. Neurological involvement was present in all four patients who died during the study period (two-tailed P value = 0.005).

Evaluation of malnutrition as a predictor of adverse outcomes in febrile neutropenia associated with paediatric haematological malignancies.

AIM: Malnutrition has been reported in the literature to be adversely associated with outcomes in paediatric malignancies. Our objective in this paper was to evaluate malnutrition as a potential predictor for adverse outcomes in febrile neutropenia associated with haematological malignancies. METHODS: A prospective observational study was performed in a tertiary care teaching hospital of Kolkata, India. Forty-eight participants, suffering from haematological malignancy, were included. Participants were included if they experienced at least one episode of febrile neutropenia. For children aged <5 years, weight for height, height for age and weight for age were used as criteria for defining malnutrition, while body mass index for age was used in children ≥5 years. A total of 162 episodes of febrile neutropenia were studied. RESULTS: Thirty patients (30/48, 62.5%) included in the study had malnutrition. In bivariate analyses at patient level, there is a strong association between malnutrition and death (odds ratio (OR) 7.286, 95% confidence interval (CI) 0.838-63.345, one-tailed P = 0.044), and life-threatening complications show a moderate trend towards significance (OR 3.333, 95% CI 0.791-14.052, one-tailed P = 0.084). Survival functions were significantly different between malnourished and non-malnourished children (log rank test χ(2) = 4.609, degree of freedom = 1, P = 0.032). Wasting was associated with life-threatening complications in children aged <5 years (OR 14, 95% CI 1.135-172.642, one-tailed P = 0.036). Logistic regression analyses at episode level revealed that phase of treatment and respiratory system involvement were significant predictors of death, while malnutrition was not. CONCLUSION: Malnutrition may be a potential predictor of mortality in febrile neutropenia.

Daniel Alcides Carrion (1857-1885) and a history of medical martyrdom.

Daniel Carrion, a sixth-year medical student, died while investigating the effects of self-inoculation of the causative organism of Oroya Fever and Bartonellosis and thereby contributed to understanding of the disease before the organisms had been identified.

Genetic defects in Indian Wilson disease patients and genotype-phenotype correlation.

Wilson disease (WD) is caused by defects in ATP7B gene due to impairment of normal function of the copper transporting P-type ATPase. This study describes a comprehensive genetic analysis of 199 Indian WD patients including mutations detected in our previous studies, undertakes functional assessment of the nucleotide variants in ATP7B promoter and correlates genotype with disease phenotype. The patient cohort harbors a total of 10 common and 48 rare mutations in the coding region of ATP7B including 21 novel changes. The common mutations represent 74% of characterized coding mutant alleles with p.C271X (63/260) and p.G1101R (7/31) being the most prevalent in eastern and western Indian patients, respectively. The mutation spectrum between east and west is mostly different with only three mutations (p.G1061E, p.N1270S and p.A1049A-fs) being shared between both the groups. Eight novel and 10 reported variants have been detected in the promoter and non-coding regions (5' and 3'UTRs) of ATP7B. Promoter reporter assay demonstrated that 3 novel variants and 5 reported polymorphisms alter the gene expression to a considerable extent; hence might play important role in ATP7B gene regulation. We devised the neurological involvement score to capture the spectrum of neurological involvement in WD patients. By utilizing the age at onset, neurological involvement score and ATP7B mutation background, we generated a genotype-phenotype matrix that could be effectively used to depict the phenotypic spectra of WD affected individuals and serve as a platform to identify prospective "outliers" to be investigated for their remarkable phenotypic divergence.

From the editors of a student journal.

Formal training in research is lacking most of the medical training programs of the world. Research can be of great help in producing more physician scientists. Students' journals can encourage research amongst medical students. But student journals face a lot of problems. The editors are students who are busy with their curricula. Moreover, there is no compensation. Additionally, since, not many student journals are visible, students doing research try and submit to prestigious journals and when face rejection, get de-motivated. There is no single solution to all the problems faced by a student journal. However, it needs to be appreciated that they are a necessity, hence, they should be encouraged actively. Collaboration between the multiple stakeholders involved (funding agencies, institutions, experts on biomedical ethics, student researchers and their faculty mentors) is the need of the hour to further expand and empower the existing student journals and set up new ones.