A randomised controlled trial to evaluate the effectiveness of a culture and disease-specific, patient-centric multi-component tobacco cessation intervention package for the patients attending non-communicable disease clinics in Punjab, India.

BACKGROUND: Developing an infrastructure to support tobacco cessation through existing systems and resources is crucial for ensuring the greatest possible access to cessation services. The present study aims to evaluate the effectiveness of a newly developed multi-component cessation among tobacco users in Non- Communicable Disease (NCD) clinics, functioning under the National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases, & Stroke (NPCDCS) of the Government of India. METHODS: The intervention package consisting of culture- and disease-specific four face-to-face counselling sessions, pamphlets, and short text messages (bilingual) with follow-ups at 3rd, 6th, and 9th months with an endline assessment at 12th months was delivered to the intervention arm of the two-arm- parallel group randomised controlled trial at two selected NCD clinics. Self-reported seven-day abstinence, frequency of use, expenditure in seven days at each follow-up, FTND score, stage of change and plasma cotinine values were assessed at baseline, follow-ups, and endline (using Liquid Chromatography -Mass Spectrometry), as applicable. RESULTS: The intervention arm reported a significantly more reduction in self-reported frequency of tobacco use at 6 months (mean: 13.6, 95% CI (7.8-19.4)), 9 months (mean: 20.3, 95% CI (12.2-28.4)) and 12 months (mean: 18.7, 95% CI (8.7-28.7)). The plasma cotinine concentration at endline in the intervention arm was statistically significantly lower than the baseline concentration. CONCLUSION: Strengthening existing health systems is crucial for offering cessation support in the resource-restraint setting of LMICs to assist in quitting sustainably.

Comprehensive Genomic Analysis Identifies a Diverse Landscape of Sideroblastic and Nonsideroblastic Iron-Related Anemias with Novel and Pathogenic Variants in an Iron-Deficient Endemic Setting.

Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings because of a lack of awareness or a methodical screening approach. Hence, we systematically evaluated anemia cases (2019 to 2021) based on clinical phenotype, normal screening tests (high-performance liquid chromatography, α gene sequencing, erythrocyte sedimentation rate, C-reactive protein, and tissue transglutaminase), and abnormal iron profile by targeted next-generation sequencing (26-gene panel) supplemented with whole-exome sequencing, multiplex ligation probe amplification/mitochondrial DNA sequencing, and chromosomal microarray. Novel variants in ALAS2, STEAP3, and HSPA9 genes were functionally validated. A total of 290 anemia cases were screened, and 41 (14%) enrolled for genomic testing as per inclusion criteria. Comprehensive genomic testing revealed pathogenic variants in 23 of 41 cases (56%). Congenital sideroblastic anemia was the most common diagnosis (14/23; 61%), with pathogenic variations in ALAS2 (n = 6), SLC25A38 (n = 3), HSPA9 (n = 2) and HSCB, SLC19A2, and mitochondrial DNA deletion (n = 1 each). Nonsideroblastic iron defects included STEAP3-related microcytic anemia (2/23; 8.7%) and hypotransferrenemia (1/23; 4.3%). A total of 6 of 22 cases (27%) revealed a non-iron metabolism gene defect on whole-exome sequencing. Eleven novel variants (including variants of uncertain significance) were noted in 13 cases. Genotype-phenotype correlation revealed a significant association of frameshift/nonsense/splice variants with lower presentation age (0.8 months versus 9 years; P < 0.01) compared with missense variants. The systematic evaluation helped uncover an inherited iron defect in 41% (17/41) of cases, suggesting the need for active screening and awareness for these rare diseases in an iron-deficient endemic population.

B12 Deficiency is the Commonest Cause of Anaemia During Pregnancy in Northern India: Study from a Tertiary Care Institute.

Iron deficiency anemia is considered the leading cause of anemia during pregnancy; however, there is a lack of comprehensive studies on the etiological factors of anemia in pregnant women. The objective of this study was to systematically investigate the causes of anemia in pregnancy. Five hundred women with hemoglobin levels < 11 g/dl between 6 and 40 weeks of pregnancy underwent a complete hemogram, iron studies, serum folate, serum B12, serum copper, and serum zinc level assessments using standard methods. The median age of the patients was 26 years (range 24-29 years). The majority of patients were in the third trimester (449/500, 89.8%). Among the patients, 325 (65%) had vitamin B12 deficiency, with 159 (31.8%) having isolated B12 deficiency and 142 (28.4%) having combined B12 and iron deficiency. Isolated iron deficiency anemia was present in 74 patients (14.8%). Additionally, 28 patients (5.6%) had beta-thalassemia minor, and anemia of chronic disease was found in 17.2% (86) of the patients. Vitamin B12 deficiency was the most common cause of anemia, followed by combined B12 and iron deficiency. Further studies in diverse populations are warranted as they have broader implications for nutrient supplementation during pregnancy. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01682-x.

Gut microbiota of preterm infants in the neonatal intensive care unit: a study from a tertiary care center in northern India.

Introduction: Disruptions of the gut microbiota of preterm infants admitted to the neonatal intensive care unit (NICU) during the first 2 weeks of life are of critical importance. These infants are prone to various complications, including necrotizing enterocolitis (NEC) and sepsis. Studying the gut microbiota will improve outcomes in preterm infants. In the present study, we examined the gut microbiota of preterm infants admitted to the NICU in the first month of life. Methods: Neonates admitted to the NICU were recruited, and stool samples were collected weekly from the seventh day of the infant's life until the 30th day of life. DNA was extracted using a DNeasy Powersoil DNA isolation kit. 16S rRNA gene sequencing targeting the V3-V4 region was performed using the MiSeq platform. Sequenced reads were processed on DADA2 pipeline to obtain an amplicon sequence variant (ASV) table. All bioinformatic and statistical analyses were performed using different packages in the R statistical framework. Results: Fourteen preterm infants were recruited, and 48 samples were collected. Alpha diversity metrics, observed ASV count, and Shannon index were found to have no differences in any clinical variables. Permutational multivariate analysis of variance (PERMANOVA) showed discrimination of neonates by gestational age and administration of probiotics. Differential abundance analysis showed a decreased abundance of Bifidobacterium Breve in extremely preterm infants (gestational age <28 weeks) compared to moderate preterm infants (gestational age 29-32 weeks). Supplementation with probiotics decreased Acinetobacter and increased Bifidobacterium in the gut of preterm neonates regardless of gestational age. Conclusion: Gestational age and probiotic supplementation alter the gut microbiota of preterm infants admitted to the NICU.

Genomics of iron refractory iron deficiency anemia phenotype reveals a spectrum of novel pathogenic biallelic and monoallelic TMPRSS6 variants and rare overlapping disorders.

The study highlights genomic findings in a series of 13 IRIDA phenotype cases. All had microcytic hypochromic anemia with suboptimal oral iron response to two different oral iron preparations at 4-6 weeks and low-normal ferritin, low transferrin saturation, and inappropriately high hepcidin. Targeted NGS on a 26-gene iron panel revealed pathogenic TMPRSS6 variants in 5/13 (38 %) cases. In addition, 2 (15 %) cases revealed rare SMAD4 and TBXAS1 gene variants that can present with refractory anemia but were consistent with diagnosis of hereditary hemorrhagic telangiectasia and Ghosal hematodiaphyseal dysplasia respectively.

Expanding the clinical and immunological phenotype of prolidase deficiency: A case report.

Prolidase deficiency (PD) is a rare autosomal recessive disorder associated with recurrent infections, immune dysregulation, and autoimmunity. PD is characterized by persistent dermatitis, skin fragility, and non-healing ulcerations on the lower limbs as its main dermatologic characteristics. Herein, we report a boy with PD due to a novel variant in PEPD who had abnormal facies, cognitive impairment, corneal opacity, recurrent infections, and persistent non-healing leg ulcers. Th17 lymphocyte counts and phosphorylated-STAT5 expression following IL-2 stimulation were reduced in our patient as compared to healthy control.

Methylmalonic aciduria as a biochemical marker for mitochondrial DNA depletion syndrome in patients with developmental delay and movement disorders: a case series.

Background: Mitochondrial DNA (mtDNA) depletion syndromes (MDDS) are genetically and clinically variable disorders resulting from a reduction in mtDNA content in the cells, tissues, and organ systems, leading to symptoms related to energy deficits. Deficiency of the mitochondrial succinyl-CoA ligase/synthetase enzyme secondary to pathogenic variations in the SUCLG1 and SUCLA2 genes is a subtype of MDDS that presents with neurological manifestations and a specific biochemical profile. Methods: This cross-sectional series describes five patients with MDDS secondary to pathogenic variations in the SUCLG1 and SUCLA2 genes from two tertiary care centers in Canada and India. Clinical data concerning the course, investigations, and outcome were gathered through chart reviews. Results: All subjects presented in early infancy with neurological manifestations, including movement disorder, psychomotor regression, developmental delay, hearing loss, behavioral issues, or a combination thereof. Elevated methylmalonic acid metabolites, an abnormal acylcarnitine profile, and lactic acidemia were noted in the biochemical profile of each patient (n = 5/5, 100%). Molecular genetic testing disclosed the presence of pathogenic homozygous mutations in four subjects and compound heterozygosity in one subject. Conclusion: MDDS associated with SUCLG1 and SUCLA2 genes can be detected biochemically by the presence of methylmalonic aciduria besides the elevation of lactate, C3, C4DC, and C5-OH acylcarnitine. Conducting metabolic workups including MMA and acylcarnitine profiles in patients with heterogeneity of clinical symptoms associated with the presence of this biochemical marker may potentially reduce the time to diagnosis and management.

The Spectrum of Inherited Gray Matter Degenerative Brain Disorders (DBD) in Children: A Single-Center Study.

Objectives: To study the clinical spectrum of inherited gray matter degenerative brain disorders (DBD) in children. Methods: This cross-sectional study evaluated children up to 12 y of age, diagnosed with an inherited gray matter DBD in a tertiary care pediatric hospital between July 2019 and December 2020. Results: A total of 314 children with progressive neuroregression were screened. Of these, 117 children with inherited gray matter DBD were included in the study. The clinic-based prevalence of DBD was 8.2%, and inherited gray matter DBD was 3.1%. The proportion of the inherited gray matter DBD was 37.3% among the overall DBD cases. Children were categorized into three groups based on the age at onset of disease: below 2 years (N = 57, 48.7%), between 2 and 5 years (N = 32, 27.3%), and between 6 and 12 years (N = 28, 23.9%). Based on the predominant cerebral structure involved, gray matter DBD were classified as cerebral gray matter disorders (53%), basal ganglia disorders (34.1%), and cerebellar disorders (12.8%). Overall, the most common disorders were Wilson disease (18%), neuronal ceroid lipofuscinosis (NCL) (17%), and neurodegeneration with brain iron accumulation (NBIA) (16%). The most common gray matter DBD in children <2 years of age were NBIA (n = 11), Rett syndrome (n = 11), and gangliosidoses (n = 10). NCL (n = 14) and ataxia telangiectasia (n = 6) were most common in the age group of 2-5 years. Wilson disease (n = 19) was the most common disorder in the age group of 6-12 years followed by NCL (n = 4) and NBIA (n = 3). Conclusion: Our study highlights the burden and spectrum of gray matter DBD in children. The clinic-based prevalence of DBD was 8.2%, and of inherited gray matter DBD was 3.1%. The proportion of inherited gray matter DBD was 37.3% among the overall DBD cases. Wilson disease, NCL, and NBIA are the most common gray matter DBD in children. Timely diagnosis is important for the prevention of recurrence in subsequent pregnancies.

Otolith microchemistry of freshwater indigenous minor carp (Bangana dero) as a biomonitoring tool to trace heavy metals in River Sutlej, Ropar Wetland (Ramsar site), Punjab, India.

The elemental composition of the fish otolith may represent a permanent record of the environmental condition the fish inhabited. Fish otolith grows incrementally from the core to a marginal region that acts as a repository of trace metal signatures. The present study explores the potential application of otolith microchemistry of the benthopelagic indigenous minor carp Bangana dero sampled from the Ropar wetland on River Sutlej, Punjab. The concentration of sixteen metals was evaluated in the otolith (n = 42) and water (n = 48) for the post-monsoon and pre-monsoon season from 2020 to 2022 using inductively coupled plasma mass spectrometry (ICP-MS) followed by element detection in the core and marginal region of whole otolith, using energy-dispersive mass spectroscopy (EDS). All the heavy metals exhibited an increase in metal concentrations in fish otolith than water during the post-monsoon season. By indices approach, the otolith was found to have a high bioaccumulation factor for Se in the post-monsoon and Hg in the pre-monsoon. Certain trace metals like As and Hg exhibited fluctuations in their core and marginal region. Thus, trace metal patterns in the otolith could act as a potential tool for monitoring the seasonal changes of metals in water bodies. The EFHg, EFSe and EFAs in the fish otolith predicted its anthropogenic source, while the remaining studied elements showed ambient water origin. Thus, using the otoliths of Bangana dero as a long-term monitoring tool in the future may be helpful for environmental assessments and the reconstruction of historical exposure for safeguarding of water bodies.

Dysregulated Genes and Signaling Pathways in the Formation and Rupture of Intracranial Aneurysm.

Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture.

Knowledge and experiences of healthcare workers in managing children with neurometabolic disorders in a developing country: a cross-sectional study.

OBJECTIVE: To evaluate the knowledge and experiences of healthcare workers in the management of neurometabolic disorders. METHODS: A cross-sectional study was carried out among the 132 participants of a continued medical education program conducted in the Department of Pediatrics at a tertiary-care teaching hospital. A questionnaire-based feedback form was circulated among the participants, and their responses were analyzed. RESULTS: Ninety-three responses were analyzed. The most common pediatric illnesses identified were infections (91%), nutritional (91%), birth-related injuries (44.4%) and metabolic disorders (44.4%). Consanguinity (81.5%) and genetic heterogeneity (42.4%) were recognized as most important causes of neurometabolic disorders. Important steps identified for prevention were prenatal testing (65.6%) and newborn screening at birth (61%); while for improving the diagnosis were routine availability of metabolic investigations (65.3%) and screening at birth (46.6%). Most respondents (58.7%) expressed discomfort in managing a case with inherited metabolic defect due to a lack of knowledge (46.8%) and diagnostic facilities (44.6%). Despite access to testing in the majority, a high cost of testing was noticed for biochemical and genetic investigations. The majority of participants (73%) considered some of the inherited metabolic disorders as treatable. Dietary substitution (89.3%), enzyme replacement (69%), cofactor replacement (53.6%), gene therapy (35.7%) and regular dialysis (16.7%) were considered the treatment options. CONCLUSION: In spite of growing awareness of inherited metabolic disorders, there are still gaps in knowledge among healthcare workers. It is challenging to diagnose and manage these disorders. Cost-reduction of diagnostic tests, routine newborn screening and increased educational activities are key challenges to be addressed.

Rat BM-MSCs secretome alone and in combination with stiripentol and ISRIB, ameliorated microglial activation and apoptosis in experimental stroke.

BACKGROUND: Stroke, a devastating neurological emergency, is the leading cause of worldwide mortality and functional disability. Combining novel neuroprotective drugs offers a way to improve the stroke intervention outcomes. In the present era, the combination therapy has been proposed as a plausible strategy to target multiple mechanisms and enhance the treatment efficacy to rescue stroke induced behavioral abnormalities and neuropathological damage. In the current study, we have investigated the neuroprotective effect of stiripentol (STP) and trans integrated stress response inhibitor (ISRIB) alone and in combination with rat bone marrow derived mesenchymal stem cells (BM-MSCs) secretome in an experimental model of stroke. MATERIALS & METHODS: Stroke was induced in male Wistar rats (n = 92) by temporary middle cerebral artery occlusion (MCAO). Three investigational agents were selected including STP (350 mg/kg; i.p.), trans ISRIB (2.5 mg/kg; i.p.) and rat BM-MSCs secretome (100 µg/kg; i.v). Treatment was administered at 3 hrs post MCAO, in four doses with a 12 hrs inter-dose interval. Post MCAO, neurological deficits, brain infarct, brain edema, BBB permeability, motor functional and memory deficits were assessed. Molecular parameters: oxidative stress, pro inflammatory cytokines, synaptic protein markers, apoptotic protein markers and histopathological damage were assessed. RESULTS: STP and trans ISRIB, alone and in combination with rat BM-MSCs secretome, significantly improved neurological, motor function and memory deficits along with significant reduction in pyknotic neurons in the brain of post MCAO rats. These results were correlating with significant reduction in pro-inflammatory cytokines, microglial activation and apoptotic markers in the brain of drug treated post MCAO rats. CONCLUSION: STP and trans ISRIB, alone and in combination with rat BM-MSCs secretome, might be considered as potential neuroprotective agents in the acute ischemic stroke (AIS) management.

Association of Micronutrients with Tuberculosis Development in HIV Infected Patients.

Human immunodeficiency virus (HIV) infection associated with weakened immune system due to decreased CD4 T cell count favors development of tuberculosis. Effector immune responses are also associated with micronutrient status due to their prominent role in maintaining immune functions. Micronutrient deficiencies are quite common among HIV patients that further result into compromised immunity thus making the conditions even more favorable for mycobacteria to establish disease. So, current study was designed to assess association of different micronutrients with development of TB in HIV patients. Micronutrient levels were measured in asymptomatic HIV patients who were monitored for the development of TB during follow up period (incident TB) within one month to one year and also in symptomatic microbiologically confirmed HIV-TB patients. Among various micronutrients assessed, levels of ferritin were found to be significantly increased (p < 0.05) with significant decreased zinc (p < 0.05) and selenium (p < 0.05) levels in incident TB group as well as in HIV-TB subjects compared to asymptomatic HIV patients who did not develop TB in the follow up period. Importantly, increased levels of ferritin and decreased levels of selenium were significantly associated with development of tuberculosis in HIV patients.

The Challenge of Severe Acute Malnutrition in Inborn Errors of Metabolism: Does Medical Food Alone Suffice?

Glutaric aciduria type 1 (GA-1) is a treatable inborn error of metabolism caused by glutaryl-CoA dehydrogenase deficiency. This enzyme deficiency leads to accumulation of glutaric acid, 3-hydroxy glutaric acid, and glutaconic acid which are potentially neurotoxic. Patients with GA-1 have characteristic clinical and neuroimaging features that help us to clinch the diagnosis. Early diagnosis by newborn screening helps us to prevent the motor problems such as dystonia and spasticity. Treatment includes low-protein diet along with carnitine supplementation which may lead to deficiency of essential amino acids and hence malnutrition. Managing malnutrition in a child with inborn errors of metabolism (IEM) is challenging. Here, we describe a patient, a case of GA-1 on medical food, presenting with severe acute malnutrition, who improved with a combination of medical and home-made foods along with lysine-free, tryptophan-reduced amino acid supplements.

Novel device for automating exchange transfusions through umbilical venous route in neonates.

Manually performed double-volume exchange transfusion (DVET) is tedious, error-prone, and may incur the risk of embolism. We aimed to develop a device that automates the DVET procedure performed through the umbilical venous route. We evaluated changes in blood passing through the device during DVET. We developed an electro-mechanical device with accessories (tubing and valve assembly) to perform a complete DVET. It comprises two syringes driven by a common pump that moves back and forth to withdraw aliquots of the patient's blood and infuse equal volumes of donor blood. In tandem, it draws donor blood from a blood bank bag and pushes the patient blood drawn from the previous cycle into a waste bag, respectively. One-way duckbill valves and a two-way pinch valve ensure the separation of the donor and patient blood. A sensor detects bubbles and clots. A dashboard displays set and measured parameters. We tested the accuracy of the delivered flow rate and volume, electrical safety, embolus detection, and changes in hematological and biochemical values. The delivered flow and volume were within 5% of the set parameters. All electrical safety parameters were within normal limits. The sensor consistently detected microbubbles and clots. There were no clinically significant differences in laboratory parameters between samples drawn directly from the blood bank bag and drawn from the exit port at 80, 100, 120, and 160 s with a fixed aliquot volume. CONCLUSIONS: Our prototype of a novel device can safely automate a DVET. Further trials of this device are warranted. WHAT IS KNOWN: • Double volume exchange transfusion is often performed manually, but this is time-consuming and error-prone. • Previous attempts at automation were not widely adopted because they involved inserting two catheters and did not have mechanisms to prevent embolism. WHAT IS NEW: • This novel device fully automates double volume exchange transfusions through a single-lumen umbilical venous catheter. • It prevents air and clot embolism and has a screen for input and output parameters and alarms.

Estimation of iron overload with T2*MRI in children treated for hematological malignancies.

Iron overload may contribute to long-term complications in childhood cancer survivors. There are limited reports of assessment of tissue iron overload in childhood leukemia by magnetic resonance imaging (MRI). A cross-sectional, observational study in children treated for hematological malignancy was undertaken. Patients ≥6 months from the end of therapy who had received ≥5 red-cell transfusions were included. Iron overload was estimated by serum ferritin (SF) and T2*MRI. Forty-five survivors were enrolled among 431 treated for hematological malignancies. The median age at diagnosis was 7-years. A median of 8 red-cell units was transfused. The median duration from the end of treatment was 15 months. An elevated SF (>1,000 ng/ml), elevated liver iron concentration (LIC) and myocardial iron concentration (MIC) were observed in 5 (11.1%), 20 (45.4%), and 2 (4.5%) patients, respectively. All survivors with SF >1,000 ng/ml had elevated LIC. The LIC correlated with SF (p < 0.001). MIC lacked correlation with SF or LIC. Factors including the number of red-cell units transfused and duration from the last transfusion were associated with elevated SF (p = 0.001, 0.002) and elevated LIC (p = 0.012, 0.005) in multiple linear regression. SF >595 ng/ml predicted elevated LIC with a sensitivity of 85% and specificity of 91.6% (AUC 91.2%). A cutoff >9 units of red cell transfusions had poor sensitivity and specificity of 70% and 75% (AUC 76.6%) to predict abnormal LIC. SF >600 ng/ml is a robust tool to predict iron overload, and T2*MRI should be considered in childhood cancer survivors with SF exceeding 600 ng/ml.

Serum Periostin Level in Children with Asthma.

OBJECTIVES: To determine the average serum periostin level in children with asthma between 6 and 16 y of age, and to find out if the levels correlated with markers of eosinophilic inflammation, asthma control, and severity. METHODS: Children under follow-up at a tertiary care centre were enrolled. Children with conditions causing elevated serum periostin other than asthma, or history of systemic steroid use in the past 6 mo were excluded. Serum total IgE and periostin were estimated by ELISA. RESULTS: The median (IQR) serum periostin level was 52.6 (45.4, 58.3) ng/mL. Levels did not vary with age, gender, duration of symptoms, positive family history, or history of exacerbations in the last 6 mo. There was no significant correlation with anthropometric parameters or their z scores, or markers of eosinophilic inflammation in blood including serum total IgE, eosinophil percentage or absolute eosinophil count. There was no difference in median periostin levels of children with different asthma symptom control or asthma severity. CONCLUSIONS: In a group of 26 Indian children with physician-diagnosed asthma, serum periostin showed no significant correlation to markers of eosinophilic inflammation.

Combination therapy with lansoprazole and cholecalciferol is associated with a slower decline in residual beta-cell function and lower insulin requirements in children with recent onset type 1 diabetes: results of a pilot study.

OBJECTIVE: To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual ß-cell function and glycemic control in children with new-onset type 1 diabetes. METHODS: Children aged 6-12 years with type 1 diabetes were allocated to receive cholecalciferol and lansoprazole (Group 1) or no treatment (Group 2). Children were maintained on their respective insulin regimens and kept records of blood sugar and insulin doses taken. Children were followed at three-month intervals for six months. Changes in mean fasting C-peptide and HbA1c levels, daily insulin doses, fasting blood glucose and mean blood glucose levels from baseline to end of the study were analyzed. RESULTS: Twenty-eight children (14 per group) met the eligibility criteria. Fasting C-peptide levels decreased significantly from baseline to study end in both groups (mean decrease -0.19±0.09ng/mL and -0.28±0.08ng/mL, p=0.04 and p=0.001; Group 1 and Group 2 respectively). However, fasting C-peptide level drop was significantly smaller in Group 1 compared to Group 2 (30.6% and 47.5% respectively; p=0.001). Likewise, daily insulin doses decreased significantly in both groups (-0.59±0.14units/kg and -0.37±0.24units/kg respectively; p=0.001). All patients recruited completed the study. No adverse events were reported. CONCLUSION: Combined therapy with cholecalciferol and lansoprazole for six months was associated with smaller decline in residual ß-cell function and lower insulin requirements in children with new-onset type 1 diabetes. Preliminary findings of this small-scale study need to be confirmed by larger studies. REGISTRY OF CLINICAL TRIALS: (www.ctri.nic.in) under number REF/2021/03/041415 N.

Peripheral Neuropathy in Children With Chronic Kidney Disease: Are We Looking Enough?

Background: Peripheral neuropathy in chronic kidney disease (CKD) is the most common neurological complication. We aimed to look at the prevalence and patterns of neuropathy in children with CKD. Methods: This cross-sectional study was conducted over 1 year in children with CKD, stage III and above. Nerve conduction studies (NCS) were performed as per standard protocols using surface electrodes on the muscles and by supramaximal stimulation of the corresponding nerves. Presence of electrophysiological abnormalities in the absence of clinical symptoms or signs was considered as subclinical neuropathy. Results: Nearly 45 children were evaluated. The majority were males (n = 39, 86.7%). The mean age was 7.9 ± 3 years (range 2-14). The mean estimated glomerular filtration rate (GFR) at enrolment was 23.3 ± 14.6 mL/min/1.73 m2 (range 5-67). The majority of children were in stage III (n = 19, 42%), followed by stages V (n = 15, 33%) and IV (n = 11, 25%). There was no evidence of clinical neuropathy; 13 children (29%) showed subclinical neuropathy. All the nerves had an axonal pattern of involvement. Motor polyneuropathy was most common type of peripheral neuropathy. The commonest nerves involved were tibial and common peroneal nerves. There were no biochemical or clinical predictors of neuropathy in our cohort. Conclusion: The prevalence of subclinical neuropathy is high in children with CKD, stage III and above. Axonal motor polyneuropathy is the predominant pattern. Electrophysiological assessment of nerve function should be routinely done in children with advanced stages of CKD to prevent chronic complications.

Comprehensive assessment of cardiovascular disease risk in children with short stature due to isolated growth hormone deficiency: a case-control study.

OBJECTIVES: Growth hormone deficiency (GHD) in adults is associated with an increased risk of cardiovascular morbidity and mortality. Although children with GHD are also believed to have a similar cardiovascular disease (CVD) risk beginning at an early age, the available data in children is scarce. We aimed to determine the various CVD risk parameters in children with isolated GHD (IGHD). METHODS: A cross-sectional case-control study was conducted at a tertiary care centre in North India comparing various auxological, biochemical, and echocardiographic parameters between 20 IGHD children aged 5-15 years and their age and sex-matched healthy controls. RESULTS: The mean age of children with IGHD and controls was similar (10.5 ± 2.6 yr vs. 9.9 ± 2.7 yr, p=0.48). Children with IGHD had significantly higher waist-hip-ratio (p=0.01), total cholesterol (p=0.02), non-high-density lipoprotein-cholesterol (p=0.02), serum homocysteine (p<0.001), C-reactive protein (CRP) (p=0.01) and pro-brain natriuretic peptide (pro-BNP) (p=0.04) levels as compared to healthy controls. Left ventricular mass (LVM) and interventricular septal thickness were significantly lower (p=0.04; p=0.02) in IGHD children. Correlation analysis showed that pro-BNP and CRP levels had negative correlation (p<0.001, r=-0.70; and p=0.04, r=-0.44, respectively) and LVM had a positive correlation (p=0.02, r=0.53) with height SDS among IGHD children. CONCLUSIONS: Children with IGHD showed abnormalities in several biochemical and cardiac parameters that may be associated with an increased CVD risk in later life. More extensive studies, including younger children with IGHD, are needed to determine the lower ages at which the CVD risk is detectable.