Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration.

Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.

Not Just Small Adults: Considerations for Pediatric Chronic Kidney Disease.

Chronic kidney disease (CKD), including pediatric CKD, is a global public health concern. Pediatric CKD has lasting effects into adulthood. In this review, we focus on the etiology of pediatric CKD and unique aspects that should be considered in treating a child with CKD, such as ensuring adequate nutrition and assessing growth hormone axis dysregulation.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Treatment of Anemia in Chronic Kidney Disease: Guidelines for South Asia.

This guideline addresses the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) in patients >18 years with chronic kidney disease (CKD) and anemia in South Asia (Bangladesh, Bhutan, Nepal, India, Pakistan, Sri Lanka). It also summarizes recommendations for anemia treatment for individual HIF-PHI molecules under two categories: dialysis-dependent and non-dialysis-dependent CKD patients. The recommendations do not apply to pediatric (≤12 years) and adolescent (12 to 18) patients or those with primary anemia or anemia secondary to other causes such as blood loss, cancer (any type), polycystic kidney disease and infectious diseases.

Safety and efficacy of a fitusiran antithrombin-based dose regimen in people with hemophilia A or B: the ATLAS-OLE study.

Fitusiran, a subcutaneous investigational siRNA therapeutic, lowers antithrombin (AT) to increase thrombin generation and rebalance hemostasis in people with hemophilia. This phase 3 open-label extension study (ATLAS‑OLE, NCT03754790) evaluated safety and efficacy of antithrombin-based dose regimen (AT-DR) in males ≥ 12 years with severe hemophilia A/B, with/without inhibitors. The original 80 mg monthly (QM) dose regimen (ODR) was optimized to AT-DR targeting AT activity levels 15-35% to mitigate thrombotic risk (starting dose 50 mg once every 2 months [Q2M], individually adjusted to 20 mg Q2M or 20/50/80 mg QM as needed).

Discrimination against patients from Bangladesh: striking at the heart of medical ethics.

We draw attention to the World Medical Association's (WMA) International Code of Medical Ethics [1] as the benchmark of medical ethics, in the face of inflammatory and discriminatory statements issued by some senior Indian doctors against Bangladeshi patients. These statements followed allegations that the Indian tricolor and Hindus had been insulted in Bangladesh. The Indian mainstream media carried these statements uncritically.

Pathways for India to Reduce Ambient Air Pollution Health Burden and Achieve the Sustainable Development Goal (SDG-3.4).

Sustainable Development Goal 3.4 (SDG-3.4) aims to reduce non-communicable disease (NCD) mortality by one-third by 2030, compared to 2015 levels.

Predictive factors of poor surgical outcome in thoracic ossified ligamentum flavum: A multivariate analysis.

Objective: Ossified ligamentum flavum (OLF) of the spine is a rare cause of compressive myelopathy. OLF is prevalent in Asian countries. Surgery is the only treatment option for symptomatic patients.

Impact of scaling up of kangaroo mother care on neonatal mortality among babies born with birth weight <2000 g in a district in southern India: a prospective cohort analysis.

Objective: To assess the impact of scaling up of kangaroo mother care (KMC) on neonatal mortality among babies born with birth weight <2000 g across an entire district in southern India.

Design Setting And Participants: Within an implementation research setting, analysis of a prospective birth cohort of babies with birth weight <2000 g born during March-December 2018 in Koppal district of Karnataka state, India, to estimate the incidence, risk and HRs of neonatal mortality associated with KMC.

Intervention: Initiation and maintenance of KMC.

Is Surgery for Congenital Heart Defects in Neonates, Infants, and Children More Challenging and Demanding Than Surgery for Acquired Heart Defects in Adults?

Pediatric cardiac surgery is a highly challenging medical subspecialty requiring technical precision, adaptability, and extensive multidisciplinary support. Unlike adult cardiac surgery, which often addresses standardized acquired conditions, surgery for congenital heart disease (CHD) in neonates, infants, and children involves unique anatomical and physiological complexities. These patients often need individualized surgical plans, and many benefit from staged interventions to accommodate growth.

Cytology Triage for HPV-Positive Postmenopausal Women in a Setting of Cervical Cancer Screening.

Background: Globally, cervical cytology continues to serve as the cornerstone of cervical cancer screening programs, but WHO 2021 guidelines advocate HPV DNA testing as the primary screening modality due to its heightened sensitivity. This method necessitates additional triage with cytology or colposcopy to detect precancerous lesions. Hormonal shifts and anatomical alterations in postmenopausal women may impact diagnostic outcomes in either modality.

CD34+ Hematopoietic Stem Cell Counts in Alzheimer's Disease: A Meta-Analysis.

Purpose: To assess the presence and quantity of CD34+ hematopoietic stem cells in patients with Alzheimer's disease (AD) through a meta-analysis.

Methods: A systematic search of the databases identified the observational and interventional studies reporting baseline CD34+ cell counts in AD patients. The data on mean counts and the measures of variation were extracted.

Responding to ethical dilemmas in pediatric nephrology: a framework for clinicians in varied practice settings.

Around the world, pediatric nephrologists encounter challenging clinical situations when decision-making is difficult. Ethical dilemmas occur when the best treatment choice is uncertain or when the nephrologist is constrained from providing a clearly superior treatment option due to conflict or a scarcity of resources. These include decision-making regarding burdensome treatments, disagreements between the nephrologist and parents or other healthcare providers, and inequities in access to therapies.

Unveiling the qualities of a 'good doctor': family carers' and healthcare professionals' perspective on dementia healthcare in India.

Background: The escalating prevalence of dementia in India highlights the need for effective dementia care, particularly in a context marked by limited specialized services and resources. In response to this growing challenge, we sought to contribute to the understanding of societal expectations of multidisciplinary dementia care by exploring the qualities that family carers and healthcare professionals value in dementia care professionals within a multidisciplinary team in India.

Methods: The aim of the study was to describe the perspectives of carers and healthcare professionals regarding the attributes of a 'good doctor' in the context of accessing care for individuals with dementia in India.

Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia.

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012.

Microbiological Investigations for Chikungunya Virus in Children With Acute Encephalitis Syndrome in a Non-Outbreak Setting in Southern India.

Chikungunya virus (CHIKV) is an emerging cause of acute encephalitis syndrome (AES) in India, with limited data on its role in childhood AES in southern India. We systematically evaluated children with AES in southern India during a non-epidemic period for CHIKV. Serum and cerebrospinal fluid (CSF) samples were tested for CHIKV using IgM ELISA and real-time reverse transcriptase PCR.

Predictive Factors for Esophageal Stricture Following Definitive Chemoradiotherapy in Esophageal Carcinoma.

Purpose: Concurrent Chemo-radiotherapy (CRT) offers attractive approaches providing the opportunity of cure, as well as organ preservation for patients with esophageal cancer and has now become the standard treatment for locally advanced unresectable esophageal cancers. However, one of the major concerns associated with CRT is the potential for treatment-related side effects, including strictures and fistula formation. This study aims to identify the predictors of stricture formation following definitive CRT in esophageal carcinoma.

Oculodentodigital Dysplasia Presenting as Spastic Ataxic Syndrome in an Indian Patient.

Spastic ataxic syndrome is a combination of cerebellar ataxia with spasticity and other pyramidal features. Common causes of spastic ataxic syndrome include spinocerebellar ataxia (SCA) 1, SCA2, autosomal recessive ataxia of Charlevoix-Saguenay, Friedreich ataxia, and hereditary spastic paraplegia type-7. We report a 32-year-old female who presented with unsteadiness of gait, incoordination, and tremulousness of both hands for 10 years with microphthalmia, microdontia, dental caries, and syndactyly.

Partial molar pregnancy as ruptured tubal ectopic.

Tubal molar pregnancy is extremely rare, and less than 200 cases have been reported in the literature. The incidence is approximated at 1.5 per 1 000 000 pregnancies.

Awareness & perceptions about organ donation among patient attendants in a tertiary-care hospital in South India: An observational study.

Background & objectives Numerous barriers like lack of awareness, fear of misuse and sociocultural beliefs contribute towards low rates of organ donation. In 2019, India had a donation rate of only 0.52 per million.

Secondary Prevention Medications in 17 Countries Grouped by Income Level (PURE): A Prospective Cohort Study.

Background: It is unclear whether global use of medications for secondary cardiovascular (CVD) prevention is improving over time.

Objectives: This study across 17 high-, middle- and low-income countries described variations in secondary CVD prevention medication use over a median follow-up of 12 years.

Methods: In the multinational PURE (Prospective Urban Rural Epidemiology) cohort study, we conducted a repeated cross-sectional analysis to examine temporal variations in the use of secondary prevention medications in participants with CVD.

Meeting clean air targets could reduce the burden of hypertension among women of reproductive age in India.

Background: Air pollution is one of the leading risk factors for hypertension globally. However, limited epidemiological evidence exists in developing countries, specifically with indigenous health data and for fine particulate matter (PM2.5) composition.

Adeno-associated virus-based gene therapy for hemophilia-addressing the gaps.

Adeno-associated virus-based gene therapy for hemophilia has emerged as a revolutionary treatment option, offering potential correction of clotting factor deficiency through a single intravenous infusion of functional genes directed to hepatocytes. With 3 gene therapies recently approved, this approach shows promise in transforming the lives of individuals with hemophilia. However, the complexity of gene therapy and the lack of standardization of methods in different components of this therapy can lead to unique challenges for clinical implementation.

Renal Histopathological Changes in Children With Congenital Ureteropelvic Junction Obstruction.

Renal histologic changes in congenital ureteropelvic junction obstruction (UPJO), although well documented, are sparsely studied in children. This study aims to establish a histological grading depending on the glomerular and tubulo-interstitial changes in hydronephrotic kidneys and determine correlation with age at surgery and impact on function post-pyeloplasty. A renal cortical wedge biopsy was obtained after pyeloplasty and histological changes were graded from 1 to 4.