Congenital Rubella: A Salient Cause of Congenital Heart Defects in Infants.

BACKGROUND: Structural congenital heart defects (CHD) take a huge toll of congenital defects in children in India. Limited information is available regarding modifiable risk factors for its causation. This study was planned with an aim to determine the prevalence of congenital rubella infection in Indian infants with structural CHD's. METHODOLOGY: This cross-sectional, observational study was conducted at a tertiary care hospital in Northern India over 1 year period (1 July 2016 to 30 June 2017). Infants <6 months with structural CHD were enrolled after taking informed consent from their mothers. Blood samples were collected from mother-child binomials and tested for rubella IgM and IgG antibodies. RESULTS: A total of 80 infants (M : F = 56 : 24), having mean age 69.4 (±56.5) days; were enrolled. In these infants, prevalence of congenital rubella infection (either infant's IgM rubella positive or infant's IgG rubella titers higher than mother's) was 8.75% (7/80). A total of 12.5% of studied mothers were seronegative for rubella IgG antibodies. Statistically significant association was found between the occurrence of congenital rubella and cataract (p = 0.0039), splenomegaly (p = 0.007) and microcephaly (p = 0.0084) in infants having structural CHD. CONCLUSIONS: Congenital rubella syndrome still remains an important modifiable cause for structural CHD in India. Sincere efforts for rubella elimination via further strengthening current vaccination strategy would help in decreasing burden of structural CHD in India.

Treatment of chronic non-healing ulcers using autologous platelet rich plasma: a case series.

BACKGROUND: Non-healing ulcers are a major health problem worldwide and have great impact at personal, professional and social levels, with high cost in terms of human and material resources. Recalcitrant non-healing ulcers are inevitable and detrimental to the lower limb and are a major cause of non-traumatic lower limb amputations. Application of autologous Platelet Rich Plasma (PRP) has been a major breakthrough for the treatment of non-healing and diabetic foot ulcers, as it is an easy and cost-effective method, and provides the necessary growth factors that enhance tissue healing. PRP is a conglomeration of thrombocytes, cytokines and various growth factors which are secreted by α-granules of platelets that augment the rate of natural healing process with decrease in time. The purpose of this case series was to evaluate the safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers on the lower extremity. METHODS: Autologous PRP was prepared from whole blood utilizing a rapid, intraoperative point-of-care system that works on the principle of density gradient centrifugation. Twenty Four (24) patients with non-healing ulcers of different etiologies, who met the inclusion criteria, were treated with single dose of subcutaneous PRP injections along with topical application of PRP gel under compassionate use. RESULTS: The mean age of the treated patients was 62.5 ± 13.53 years and they were followed-up for a period of 24 weeks. All the patients showed signs of wound healing with reduction in wound size, and the mean time duration to ulcer healing was 8.2 weeks. Also, an average five fold increase in the platelet concentrate was observed in the final PRP product obtained using the rapid point-of-care device, and the average platelet dose administered to the patients was 70.10 × 108. CONCLUSION: This case series has demonstrated the potential safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers. TRIAL REGISTRATION: NCT03026855 , Registered 4 January 2017 'Retrospectively'.

Glycaemic control and factors affecting it in type 1 diabetes in children: experience from a tertiary care centre in India.

INTRODUCTION: Optimal glycaemic control is essential for the prevention of future micro- and macrovascular complications in type 1 diabetes (T1D). The type of insulin, the type of insulin delivery device, the caregiver's knowledge, the patient's age, duration of diabetes, and self-monitoring of blood glucose affect glycaemic control in type 1 diabetes. In the present study, we analysed glycaemic control and factors affecting it at a tertiary care centre in northern India. MATERIAL AND METHODS: A retrospective review of records of patients registered between 2015 and 2018 was done. The data on demographic and disease-related factors were collected from the records. The different groups were compared with the t-test, one-way ANOVA, or Kruskal-Wallis test. RESULTS: The mean age at the time of evaluation was 10.43 ±4.04 years (2-21 years), and the mean disease duration was 46.61 ±28.49 months (16-141 months). Most of the patients were prepubertal and using a basal-bolus regimen. The mean glycated haemoglobin (HbA1c ) was 7.96 ±1.46%, but only 24% had HbA1c below the International Society of Paediatric and Adolescent Diabetes (ISPAD) recommended desirable level of below 7%. Forty-six patients suffered one or more micro-macrovascular complications, and dyslipidaemia was the most common complication. Children with a longer duration of disease (8.39 ±1.42% vs. 7.59 ±1.65%), an episode of DKA (diabetes ketoacidosis) within a year of evaluation (9.19 ±2.54% vs. 7.93 ±1.39%), lower maternal (8.22 ±1.37% vs. 7.56 ±1.45%) and paternal education (8.26 ±1.67% vs. 7.78 ±1.30%), and hyperthyroid state (9.43 ±2.28% vs. 7.91 ±1.45%) had higher HbA1c. CONCLUSIONS: Better diabetes education focusing on parents with lower education strata and children with longer disease duration and poor compliance can help improve glycaemic control in developing countries like India.

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.

Indian Research in Gestational Diabetes Mellitus during the Past Three Decades: A Scientometric Analysis.

BACKGROUND: India plays an important role in global research on gestational diabetes mellitus (GDM), but a bibliometric assessment of this research is lacking. OBJECTIVE: To provide a comprehensive analysis of Indian GDM research during the last 30 years using select bibliometric indicators. METHODS: The Scopus international database was used to retrieve publication data, using a defined search strategy. The analysis focused on research output of Indian authors and organizations and their collaborations. The qualitative performance was assessed in terms of relative citation index and citations per paper (CPP). RESULTS: Overall, 100 countries participated in GDM research producing 13,193 publications during 1990-2019. India ranked ninth in global output (1182 publications, 3.1% share) and CPP of 18.6. Only 21.3% of publications had international collaboration and 9.4% were funded. Of the 235 organizations and 544 authors that participated in India's research on GDM, the top 50 organizations and authors contributed 53.8 and 36.4% to national publication share, respectively. The leading productive organizations were AIIMS, New Delhi, KEMH, Pune and PGIMER, Chandigarh, whereas the most productive authors were S. Kalra, V. Seshiah and C.S. Yajnik. Indian Journal of Endocrinology and Metabolism, Journal of Clinical and Diagnostic Research, Journal of Obstetrics and Gynecology of India and Diabetes Research and Clinical Practice were the most productive journals. CONCLUSIONS: Indian research on GDM is lagging behind other countries which have a similar disease burden. Increasing national and international collaborations, and active support of national and international funding agencies is urgently required to produce quality research on GDM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13224-021-01444-7.

Neonatal seizures: A mother's blessing in disguise.

Fetus and neonate are dependent maternal supply of calcium for maintaining the calcium profile in physiologic range. The disturbances in maternal calcium homeostasis leads to changes in the baby's calcium. Maternal investigations in neonatal hypocalcemia not only reveal the etiology in the baby but are sometime helpful in unmasking maternal disorder of calcium homeostasis.

Mauriac syndrome: A failure of parent or physician.

Mauriac syndrome is rare; we share our experience of nine patients who presented at a young age with malnutrition, short stature, abdominal distention and deranged liver function.

Ten-year use of recombinant parathyroid hormone for the treatment of hypoparathyroidism in a boy with partial Jacobsen syndrome.

Pediatric hypoparathyroidism (HPT) is caused by inherited or acquired defects involving the synthesis or secretion of PTH, resistance to PTH action, or inappropriate regulation of PTH. Several syndromes such as DiGeorge syndrome, HDR (hypoparathyroidism, sensorineural deafness and renal dysplasia) syndrome, HRD (hypoparathyroidism, retardation, and dysmorphism) syndrome, Kenny-Caffey syndrome etc. may have associated HPT. In the present communication, we describe, the hitherto unreported, occurrence of HPT in a child with partial Jacobsen syndrome. Chromosomal Microarray analysis showed a heterozygous deletion of 4.7 Mb at cytoband 11q24.3q25 encompassing approximately 20 genes including JAM3 and NTM genes. The child was treated with recombinant human parathyroid hormone (rhPTH1-34) for 10 years. Throughout follow up, he required several adjustments in dosages of rhPTH1-34 and oral calcium to maintain serum calcium concentrations in low normal ranges. The bone turnover markers remained normal and oral calcium supplements were completely taken off after 8 years. In conclusion, our single-case experience indicates that long-term therapy of chronic HPT with rhPTH1-34 is safe and reduces the need for additional therapies.

Recombinant parathyroid hormone for hypoparathyroidism in children: a narrative review.

The conventional management of hypoparathyroidism in children involves the use of calcium and vitamin D analogs. This therapy effec-tively increases the serum calcium levels but worsens hypercalciuria and its consequences such as nephrocalcinosis and renal insuffi-ciency. Although replacement with the missing parathyroid hormone (PTH) is ideal and available for more than 2 decades, the reported concerns of osteosarcoma prohibited its use in children with open epiphyses. Nevertheless, the data accumulated over the past several years suggests that the fears of bone malignancies were probably overstated. With an aim to review the available data on recombinant PTH (rhPTH) use, we performed a literature search using international databases and identified 15 studies involving approximately 70 children with hypoparathyroidism due to various etiologies who received rhPTH1-34 for durations between 1 day and 13.5 years. All the studies appear to indicate that rhPTH1-34 therapy is an effective short and long-term strategy for treatment of hypoparathyroidism with better metabolic control, lesser effects on renal function and improved quality of life as compared to conventional therapy. A more significant conclusion is the safety of long-term use of rhPTH1-34 with no observed adverse skeletal effects so far. However, all studies mention the importance of a continued surveillance for adverse effects in the treated patients. This narrative review discusses the experi-ence of rhPTH1-34 use exclusively in children.

Multiple Opportunistic Infections in an 8-month-old Infant: Is it Seronegative HIV Infection?

We describe an 8-mo-old boy who presented with acute respiratory failure following a prolonged febrile respiratory illness with features suggesting immunodeficiency.

Safety and Effectiveness of Bone Marrow Cell Concentrate in the Treatment of Chronic Critical Limb Ischemia Utilizing a Rapid Point-of-Care System.

Critical limb ischemia (CLI) is the end stage of lower extremity peripheral vascular disease (PVD) in which severe obstruction of blood flow results in ischemic rest pain, ulcers and/or gangrene, and a significant risk of limb loss. This open-label, single-arm feasibility study evaluated the safety and therapeutic effectiveness of autologous bone marrow cell (aBMC) concentrate in revascularization of CLI patients utilizing a rapid point-of-care device. Seventeen (17) no-option CLI patients with ischemic rest pain were enrolled in the study. Single dose of aBMC, prepared utilizing an intraoperative point-of-care device, the Res-Q™ 60 BMC system, was injected intramuscularly into the afflicted limb and patients were followed up at regular intervals for 12 months. A statistically significant improvement in Ankle Brachial Index (ABI), Transcutaneous Oxygen Pressure (TcPO2), mean rest pain and intermittent claudication pain scores, wound/ ulcer healing, and 6-minute walking distance was observed following aBMC treatment. Major amputation-free survival (mAFS) rate and amputation-free rates (AFR) at 12 months were 70.6% and 82.3%, respectively. In conclusion, aBMC injections were well tolerated with improved tissue perfusion, confirming the safety, feasibility, and preliminary effectiveness of aBMC treatment in CLI patients.

αV ß5 and CD44 are oxygen-regulated human embryonic stem cell attachment factors.

Human embryonic stem cells (hESCs) have great potential for clinical therapeutic use. However, relatively little is known of the mechanisms which dictate their specificity of adhesion to substrates through adhesion proteins including integrins. Previous observations demonstrated enhanced clonogenicity in reduced oxygen culture systems. Here, we demonstrated via antibody blocking experiments that αV ß5 and α 6 significantly promoted hESC attachment in 2% O2 only, whereas blockage of CD44 inhibited cell attachment in 21% O2 alone. Immunofluorescence confirmed expression of αV ß5 and CD44 in both 2% O2 and 21% O2 cultured hESCs while flow cytometry revealed significantly higher αV ß5 expression in 2% O2 versus 21% O2 cultured hESCs and higher CD44 expression in 21% O2 versus 2% O2 cultured hESCs. Adhered hESCs following blockage of αV ß5 in 2% O2 displayed a reduction in nuclear colocalisation of Oct-4 and Nanog with little effect observed in 21% O2. Blockage of CD44 had the converse effect with dramatic reductions in nuclear colocalisation of Oct-4 and Nanog in 21% O2 cultured hESC which retained adherence, but not in 2% O2 cultured cells. Identification of oxygen-dependent substrate attachment mechanisms in hESCs has the potential to play a role in the development of novel substrates to improve hESC attachment and culture.