Supplementation of High-Strength Oral Probiotics Improves Immune Regulation and Preserves Beta Cells among Children with New-Onset Type 1 Diabetes Mellitus: A Randomised, Double-Blind Placebo Control Trial.

OBJECTIVES: To investigate the mechanism of glycemic control in children with type 1 diabetes (T1D) following high-strength probiotics supplementation by assessing immune-regulatory markers. METHODS: In this single-centre randomised double-blinded placebo-controlled study, children with new-onset T1D on regular insulin therapy were randomised into probiotic or placebo groups with 30 children each. The probiotics group received oral powder of Vivomixx®, and the placebo group received corn starch for six months. The primary outcome parameters included induced T regulatory cells (i-Tregs) percentage, insulin autoantibodies (IAA), insulinoma associated 2 autoantibodies (IA2), glutamic acid decarboxylase autoantibodies (GAD 65) and plasma interleukin-10 (IL-10) levels. The secondary outcome variables were changes in plasma C-peptide levels and glycemic control parameters. RESULTS: Twenty-three children in the placebo group and 27 in the probiotic group completed the study. There was a significant increase in the percentage of iTregs (3.40 in the probiotic vs. 2.46 in the placebo group; p = 0.034). Median glycated hemoglobin (HbA1c) levels significantly decreased from 68 mmol/mol (8.35%) in the placebo group to 60 mmol/mol (7.55%) in the probiotic group (p = 0.017). Median C-peptide levels were significantly higher in probiotics (0.72 ng/ml) vs. placebo group (0.11 ng/ml) (p = 0.036). The plasma IL-10 levels significantly increased in the probiotic group after six months of treatment (p = 0.002). CONCLUSIONS: The high-strength probiotics improved the immunoregulatory milieu, thereby preserving the beta-cell function and better glycemic control.

Impact of short-term application of continuous glucose monitoring system(CGMS) on long-term glycemic profile in adolescents and adults with type 1 diabetes mellitus: An open-label randomized control cross over study.

AIMS: The use of Continuous Glucose Monitoring System (CGMS) improves glycemic parameters in Type 1 Diabetes Mellitus (T1D), but the cost is prohibitive. Here, we investigated the effect of short-term application of real-time and intermittently-scanned CGMS (rt and is-CGMS) in T1D individuals on change in HbA1c at the end of 3 months. METHODS: T1D individuals were randomized into three groups in a ratio of 1:1:2 - Group A (rt-CGMS for 2 weeks initially, followed by is-CGMS for 2 weeks at 3 months), Group B (is-CGMS for 2 weeks initially followed by rt-CGMS for 2 weeks at 3 months) and Group C (only self-monitoring of blood glucose), respectively. HbA1c at baseline, 3, and 6 months were compared. RESULTS: Out of a total 68 T1D patients, HbA1c decreased significantly in groups A and B at 6 months compared to the baseline, but not in group C. HbA1c was significantly lower in Group A compared to Group C at 3 and 6 months. Fructosamine levels significantly decreased in Group B before and after cross-over. Glycemic variability indices improved significantly after cross-over from is-CGMS to rt-CGMS. CONCLUSION: Intermittent application of CGMS for 2 weeks improves short- and long-term blood glucose control in T1D.

Efficacy, safety, and dose-response effects of calcifediol supplementation on 25-hydroxyvitamin D, parathyroid hormone, and 1,25-dihydroxyvitamin D levels in healthy adults: An open-label, interventional pilot study.

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent across the globe. Cholecalciferol (Vitamin D3) fails to attain sufficient serum concentrations of 25-hydroxyvitamin D (25(OH)D) in a significant proportion of supplemented individuals. Calcifediol (25-hydroxyvitamin D3) is less studied in healthy adults and its effects on 25(OH)D, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25(OH)2D) at higher doses are not well known. MATERIALS AND METHODS: The study was an open-label, interventional trial recruiting consecutive participants with VDD who were allocated to receive either 2 capsules (50 µg-group) or 1 capsule (25 µg-group) daily doses of calcifediol. Baseline assessment included clinicodemographic parameters, dietary calcium, calcemic (calcium, inorganic phosphate, albumin, alkaline phosphatase, urine spot calcium/creatinine), and hormonal parameters (25(OH)D, PTH, and 1,25(OH)2D). Participants were followed up at 4 and 8 weeks with repeat assessments of calcemic and hormonal parameters. RESULTS: There were 64 participants, 35 (50 µg-group) and 29 (25 µg-group), without any significant difference in any of the baseline parameters. 97.1% participants in the 50 µg-group (at 4 and 8 weeks) and 93.1% (at 4 weeks) and 96.5% (at 8 weeks) in the 25 µg-group attained 25(OH)D sufficiency (≥30 ng/ml) with calcifediol. The mean serum 25(OH)D was 84.0 ± 27.7 ng/ml in the 50 µg-group and 58.0 ± 23.6 ng/ml in the 25 µg-group group at 4 weeks, which later rose to 94.3 ± 21.8 ng/ml and 76.0 ± 16.4 ng/ml, respectively, at 8 weeks. PTH levels decreased in both groups at both time points. 1,25(OH)2D rose significantly in both groups at 4 and 8 weeks but was not significantly different between both groups. There was no case of incident hypercalcemia or symptomatic nephrolithiasis. CONCLUSION: Calcifediol is a safe and efficacious alternative for oral Vitamin D supplementation in young adults. Increment in 25(OH)D levels is rapid and dose-dependent.

Normative Data on Dehydroepiandrosterone Sulphate (DHEAS) and its Attributes in Healthy Indian Children and Adolescents.

Dehydroepiandrosterone sulphate (DHEAS), the biochemical indicator of adrenarche and pubarche, is of paramount importance in the evaluation of puberty-related disorders. The reference range of DHEAS should be ethnicity, age, sex, pubarche and Tanner stage specific. Anthropometry, puberty assessment and hormonal parameters were estimated using electrochemiluminescence assay. Bone age was estimated using the BoneXpert software. Of 2191 healthy Indian children aged 5-18 y screened at Chandigarh, 1919 were included in the final analysis (994 boys). The median DHEAS levels at pubarche stage P2 were 82.10 (55.0-129.0) g/dl in girls and 132.50 (95.12-205.50) g/dl in boys. By ROC analysis, the level of DHEAS at pubarche was 63.7 g/dl (sensitivity 72.6%, specificity 64.4%) in girls and 82.2 g/dl (sensitivity 81.8%, specificity 68.8%) in boys. The median age at adrenarche was 9.5 y in both sexes. On multivariate regression analysis; bone age, body mass index (BMI), gonadal steroids, and insulin-like growth factor-1 (IGF-1) significantly correlated with serum DHEAS levels in either sex.

IL-17 A correlates with disease progression in papillary thyroid carcinoma.

BACKGROUND: Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics. METHODS: Cytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto's Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases. RESULTS: All the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression. CONCLUSIONS: Increased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.

Clinical Profile, Intensive Care Needs and Outcome of Children with Dilated Cardiomyopathy Associated with Vitamin D Deficiency: A 5-year PICU Experience.

Aim: To describe the clinical profile, treatment details, intensive care needs, and long-term outcome of children with dilated cardiomyopathy (DCM) associated with Vitamin D deficiency (VDD). Materials and methods: Case records of 14 children with DCM associated with VDD [25(OH)D3 levels <20 ng/mL] admitted to the pediatric intensive care unit (PICU) of a tertiary care teaching hospital between January 2017 and December 2021 were retrospectively analyzed for clinical features, echocardiographic findings, treatment details, intensive care needs, and outcomes. Results: The median (IQR) age was 6 (2-9) months and 71% (n=10) were males. The common modes of presentation included respiratory distress or failure (78.6%), congestive cardiac failure (71.4%), cardiogenic shock (37.5%), and seizures and encephalopathy (14.3% each). The median (IQR) serum calcium was 8.7 (7-9.5) mg%, ionized calcium 0.7 (0.7-1.1) mmol/L, alkaline phosphatase 343 (316-415) IU/L, phosphate 3.5 (2.6-4.5) mg%, PTH 115 (66-228) pg/mL, and 25(OH)D3 5 (3-7) ng/mL. The median (IQR) left ventricular ejection fraction (LVEF) at admission was 22 (17-25)%. The treatment included intravenous calcium infusion (35.7%), vitamin D supplementation in all (57.1% parenteral and 42.9% oral), mechanical ventilation (35.7%), and vasoactive drugs (57.1%). There was no mortality. The median (IQR) duration of PICU and hospital stay was 76 (31-98) hours and 6 (4.7-10) days, respectively. Out of 14 children, 10 (71.4%) were followed-up till median (IQR) of 10 (7-58) months. All were asymptomatic and had normal LEVF (except one had residual moderate mitral regurgitation). Conclusion: Vitamin D deficiency is a potentially treatable and reversible cause of DCM in children. How to cite this article: Kumar S, Randhawa MS, Angurana SK, Nallasamy K, Bansal A, Kumar MR, et al. Clinical Profile, Intensive Care Needs and Outcome of Children with Dilated Cardiomyopathy Associated with Vitamin D Deficiency: A 5-year PICU Experience. Indian J Crit Care Med 2023;27(7):510-514.

Comparing the Effectiveness of Propranolol versus Atenolol in Inducing Clinical Clearance in the Treatment of Infantile Haemangioma: A Randomised Controlled Trial.

Background: Despite the excellent clinical efficacy of oral propranolol in the management of infantile haemangiomas (IHs), there is a need to further evaluate other beta blockers that may be equally efficacious but result in lesser adverse effects. We compared the efficacy and short-term safety of atenolol, a hydrophilic cardio-selective beta blocker, with propranolol, in the treatment of IHs. Materials and Methods: Sixty patients with complicated and/or cosmetically significant IHs were randomised into two groups, oral propranolol group (2 mg/kg/day) and the oral atenolol (1 mg/kg/day) group, respectively, for 9 months. Patients were assessed clinically, by the use of Doppler ultrasonography (USG) and measurement of serum hypoxia-inducible factor 1 alpha (HIF-1α). Results: Twenty-two of 30 patients achieved complete clearance in the propranolol group (0.73; 95% CI = 0.54 to 0.87) compared with 13 of 25 patients in the atenolol group (0.52; 95% CI = 0.31 to 0.72). The mean time to achieve Physician Global Assessment Score 5 (PGA5) (25.00 ± 8.87 weeks) was significantly lesser in the propranolol group versus the atenolol group (31.69 ± 7.01 weeks; log-rank = 0.04). The two groups were comparable in terms of adverse effect profile, degree of volume reduction in USG and reduction in HIF-1α levels. Conclusions: Propranolol (2 mg/kg/day) is better than atenolol (1 mg/kg/day) in inducing complete clinical clearance of IH although the results need to be reproduced in larger studies.

Establishment and characterization of long-term human primary parathyroid tumor subclones derived from Indian PHPT.

The continuous cell line of epithelial human parathyroid cells has been proven difficult. Previously, PTH-C1 cell line was only established rat parathyroid tissue cell line known to express the parathyroid hormone-related peptide (Pthrp) gene. The paucity of continuous cell line of human parathyroid cells secreting parathyroid hormone (PTH) has imposed hurdle in in vitro assessment of the mechanisms involved in the control of parathyroid cell function and proliferation. The primary cell cultures of human parathyroid cells were derived from parathyroid adenoma tissue biopsy (n = 5). The cells were subsequently subcultured to maintained primary subclones. Karyotyping analysis was performed to analyze the genotypic identity of derived subclones. The expression of calcium-sensing receptor (CaSR) and intact parathyroid hormone (iPTH) were analyzed using immunocytochemistry and immunofluorescence. In the present study, we have used a defined condition medium to generate the continuous culture of human parathyroid cells derived from patients with parathyroid adenoma due to primary hyperparathyroidism. The subcultured primary subclones were maintained epithelial and polygonal morphology, doubling time of approximately 25 h, displaying a diploid chromosome number, and secretion of PTH. This cell line produces PTH and expresses the calcium-sensing receptor (CaSR) known to be involved in parathyroid function. Altogether these findings indicate the uniqueness of the human parathyroid cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology.

Role of serum procalcitonin in the diagnosis and monitoring of treatment response in treatment-naïve subjects with chronic pulmonary aspergillosis.

Background: Interferon-gamma (IFN-γ) down-regulates plasma procalcitonin (PCT), marker of inflammation. Chronic pulmonary aspergillosis (CPA) is associated with low IFN-γ levels. Thus, plasma PCT may be elevated in CPA and could have a role in diagnosing and monitoring treatment response in CPA. Herein, we investigate the diagnostic performance of plasma PCT in CPA. Methods: We extracted the demographic, clinical, radiological, treatment outcomes, and plasma PCT levels of CPA subjects and controls (previously treated pulmonary tuberculosis with radiological abnormalities on CT chest [diseased controls] and treatment naïve active pulmonary tuberculosis [PTB]). We treated CPA subjects with six months of oral itraconazole. We took 0.25 ng/mL as a cut-off value for PCT. The study's primary objective was to ascertain the diagnostic performance of PCT in diagnosing CPA. The key secondary outcome was to study the change in the plasma PCT levels after itraconazole therapy. Results: We included 190 CPA cases and 40 controls (diseased controls [n = 20] and active PTB [n = 20]). PCT was elevated (≥0.25 ng/mL) in only 7 (3.7%) subjects with CPA. The sensitivity and specificity of PCT (≥0.25 ng/mL) were 3.7% (1.5-7.4%) and 100 (91.2-100%), respectively. The area under the curve for plasma PCT was 0.48 (95% confidence interval, 0.39-0.58). The plasma PCT values were available in 93 subjects at six months. There was a significant decline in the median plasma levels of PCT after treatment; however, the PCT levels either increased or remained the same in 45% of the subjects. Conclusion: Plasma procalcitonin has poor performance in diagnosing and following subjects with CPA.

Incidence and risk factors for dysglycaemia in Asian-Indians: a 10-year population-based prospective cohort study.

BACKGROUND: Diabetes prevalence estimates suggest an increasing trend in South-East Asia region, but studies on its incidence are limited. The current study aims to estimate the incidence of type 2 diabetes and pre-diabetes in a population-based cohort from India. METHODS: A subset of Chandigarh Urban Diabetes Study cohort (n=1878) with normoglycaemia or pre-diabetes at baseline was prospectively followed after a median of 11 (0.5-11) years. Diabetes and pre-diabetes were diagnosed as per WHO guidelines. The incidence with 95% CI was calculated in 1000 person-years and Cox proportional hazard model was used to find the association between the risk factors and progression to pre-diabetes and diabetes. RESULTS: The incidence of diabetes, pre-diabetes and dysglycaemia (either pre-diabetes or diabetes) was 21.6 (17.8-26.1), 18.8 (14.8-23.4) and 31.7 (26.5-37.6) per 1000 person-years, respectively. Age (HR 1.02, 95% CI 1.01 to 1.04), family history of diabetes (HR 1.56, 95% CI 1.09 to 2.25) and sedentary lifestyle (HR 1.51, 95% CI 1.05 to 2.17) predicted conversion from normoglycaemia to dysglycaemia, while obesity (HR 2.43, 95% CI 1.21 to 4.89) predicted conversion from pre-diabetes to diabetes. CONCLUSION: A high incidence of diabetes and pre-diabetes in Asian-Indians suggests a faster conversion rate to dysglycaemia, which is partly explained by sedentary lifestyle and consequent obesity in these individuals. The high incidence rates call for a pressing need for public health interventions targeting modifiable risk factors.

Impulse Control Disorders with Short-term Use of Cabergoline in Macroprolactinomas: A Prospective Study with a Brief Review of Literature.

Impulse control disorders (ICDs) are less-emphasized adverse effects of dopamine agonists. Evidence on prevalence and predictors of ICDs in patients with prolactinomas is limited and confined chiefly to cross-sectional studies. This was a prospective study performed to investigate ICDs in treatment-naïve patients with macroprolactinomas (n = 15) using cabergoline (Group I), compared to consecutive patients of nonfunctioning pituitary macroadenomas (n = 15) (Group II). Clinical, biochemical, radiological parameters and psychiatric comorbidities were evaluated at baseline. ICD was assessed by Minnesota impulsive disorder interview, modified hypersexuality and punding questionnaires, South Oaks gambling scale, kleptomania symptom assessment scale, Barratt impulsive scale (BIS), and internet addiction scores (IAS) at baseline and 12 weeks. Group I had a significantly lower mean age (28.5 vs. 42.2 years) with a female predominance (60%) compared to group II. Median tumor volume was lower in group I (4.92 vs. 14 cm3) despite significantly longer symptom duration (2.13 vs. 0.80 years) than in group II. Serum prolactin decreased by 86% (P = 0.006) and tumor volume decreased by 56% (P = 0.004) at 12 weeks in group I, with a mean weekly cabergoline dose of 0.40 ± 0.13 mg. There was no difference between both groups in hypersexuality, gambling, punding, and kleptomania symptom assessment scale scores at baseline and 12 weeks. Mean BIS showed a more remarkable change in group I (16.2% vs. 8.4%, P = 0.051), and 38.5% of patients transitioned from average to above-average IAS in group I. The current study found no increased risk of ICD with short-term use of cabergoline in patients with macroprolactinomas. The use of age-appropriate scores (such as IAS in younger individuals) may help diagnose subtle alterations in impulsivity.

Incidence and predictors of metabolic syndrome in Asian-Indians: a 10-year population-based prospective cohort study.

Background: Metabolic syndrome represents aggregation of risk factors associated with an increased risk of developing type 2 diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). Assessing its incidence is an effective way for estimating the future burden of DM and ASCVD and understanding their secular trends and effect of public health measures on halting the evolution of risk factors. The present study aimed to estimate the incidence of metabolic syndrome and its predictors using a population-based cohort. Methods: A subset of Chandigarh Urban Diabetes Study cohort (n = 1023) without diabetes or metabolic syndrome was prospectively evaluated after a mean of 10.7 years. Metabolic syndrome was defined as per International Diabetes Federation criteria and diabetes as per American Diabetes Association standards. The incidence was calculated in 1000 person years, and multivariate logistic regression was used to estimate the strength of association between incident metabolic syndrome and risk factors. Results: In the followed-up individuals (n = 303), incidence of metabolic syndrome was 32.1 per 1000 person years (95% CI 26.3-38.7 per 1000 person years). Amongst those developing metabolic syndrome, ≥4 components were present in 52% individuals, with low HDL-C being the most common abnormality. Those with metabolic syndrome had a five-time higher risk of diabetes (OR: 4.94; 95% CI: 2.27-9.96; p < 0.001) and a threefold higher risk of hypertension (OR: 2.67; 95% CI: 1.30-5.48; p = 0.006). Conclusion: Asian-Indians have a high incidence rate of metabolic syndrome, which is associated with sedentary lifestyle and consequent central obesity.

Clinical and metabolic characteristics of males with early-onset androgenetic alopecia.

Background Men with early-onset androgenetic alopecia (AGA) often have an abnormal hormonal milieu. Objective To ascertain the clinico-phenotypic characteristics and the prevalence of hormonal and metabolic changes in men with early-onset AGA. Methods Consecutive male patients less than 30 years of age with a Norwood-Hamilton grade ≥3 AGA were recruited in this comparative cross-sectional study. After endocrine evaluation they were classified into two groups, that is, Group A consisting of subjects with an altered hormonal profile and Group B with normal hormonal profiles. The groups were assessed for differences in disease phenotype and severity (Norwood-Hamilton grade), insulin resistance and parameters of metabolic syndrome (ATP III guidelines). Results Altered hormonal profiles were seen in 34 of the 100 subjects with AGA, while insulin resistance and metabolic syndrome were noted in 44 and 26 respectively. Altered hormonal profiles were significantly associated with insulin resistance and severe alopecia (grade 4 and above Hamilton-Norwood Scale). Insulin resistant Group A patients had a significantly higher prevalence of severe alopecia (>grade 4) (P = 0.0036). The prevalence of metabolic syndrome was similar in both groups. Limitation The cross sectional study design was a drawback of this study. Further, a control arm without AGA was not included and the sample size of 100 was selected arbitrarily. Conclusion An altered hormonal profile and insulin resistance was noted in a third of the males with early-onset AGA. Subjects with altered hormonal profiles had a higher prevalence of insulin resistance and were likely to have severe grades of AGA.

Radioactive Iodine Uptake in Postoperative Seroma: A Cause for False Positivity.

Besides the known physiologic uptake of 131I, the literature describes various false-positive findings on 131I scans in benign lesions, inflammation, traumatic sites, and postsurgical sites, to name a few. However, to the best of our knowledge, no study has shown false-positive uptake of 131I in a postoperative seroma at the postsurgical site. We describe such a case here.

Correlation of plasma levels of itraconazole with treatment response at 4 weeks in chronic dermatophytosis: Results of a randomised controlled trial.

BACKGROUND: Itraconazole in varying doses and duration is being frequently used for the management of dermatophytosis. There is a scarcity of studies on the bioavailability of various itraconazole brands available in the market. AIMS AND OBJECTIVES: The aim of this study was to determine the plasma concentration of itraconazole of various brands and its correlation with clinical efficacy in chronic dermatophytosis. MATERIALS AND METHODS: One hundred patients with chronic dermatophytosis with age >18 years were studied at the outpatient clinic of our tertiary care hospital. Plasma itraconazole level was estimated on Week 2 and Week 4 after randomly dividing the patients into Groups A, B and C who received cap itraconazole 100 mg twice a day of innovator, multinational and local generic brands, respectively, for 4 weeks. Both efficacy (cure, partial cure or no cure), safety and recurrence were compared between the three groups. RESULTS: At 4 weeks, number of patients classified as 'cured' were 10/26 (38.4%) in Group A, 5/22 in Group B (22.7%) and 3/21 (14.2%) in Group C (p = .002). Mycological cure rates at Week 4 in Groups A, B and C were 21 (80.8%), 17 (81.0%) and 5 (26.3%), respectively (p = .006). Plasma levels of itraconazole were comparable between the three groups at Week 2 and Week 4. No statistically significant correlation was found between itraconazole levels and treatment response in any of the groups at 4 weeks. Incidence of adverse effects and recurrence rates was also similar among the three groups. CONCLUSION: Cure rates for chronic dermatophytosis were poor with all three itraconazole brands at 4 weeks of treatment. Higher cure rates were obtained with innovator drug as compared to multinational and local generic brands at 4 weeks. Plasma levels of the three drugs were however similar, indicating that factors other than serum bioavailability are at play in determining response of chronic dermatophyte infections to oral itraconazole.

Differences among Indian and European pemphigus patients based on demographics, clinical parameters and propensity for relapse: results of a prospective bicontinental cohort study.

Limited studies have explored pemphigus variations among different ethnic groups residing in their respective geographical locations. This bicontinental study aimed to compare clinical and immunological parameters in Indian and European pemphigus patients in complete remission, off therapy, or on minimal therapy. 105 patients (India, n= 75; Bulgaria, n=15; Greece, n=15) with pemphigus vulgaris (PV) or pemphigus foliaceous (PF) in complete remission on minimal therapy (n=64) or complete remission off therapy (n=41) were recruited. Demographic, clinical, and immunological parameters were compared. Indian patients were significantly younger, the maximal disease severity during the preceding active disease phase was significantly lower, and treatment duration until complete remission was significantly shorter, compared to European patients. European patients had significantly higher anti-Dsg3 serum levels and higher IgG positivity rate based on direct immunofluorescence microscopy at baseline. Furthermore, European patients revealed higher CD19, CD19+ CD27+ cell counts, compared with patients from India. Of note, none of the European patients (n=30) relapsed within the study period, in contrast to 29/75 (38.6%) Indian patients. Treatment strategies differed significantly between the two cohorts, with more frequent utilization of rituximab to achieve remission in the Indian cohort, while prednisolone was more widely used for maintaining remission in the European cohort. The observed heterogeneity of pemphigus among patients of different ethnicities in terms of demographics, clinical parameters, and propensity for relapse may be due to genetic background or different treatment strategies.

Role of cytotoxic T cells and PD-1 immune checkpoint pathway in papillary thyroid carcinoma.

Background: Lymphocytic thyroiditis (LT) is frequently seen in the tumor microenvironment (TME) of papillary thyroid carcinomas (PTCs). However, the characteristic of these tumor-infiltrating lymphocytes (TILs) is not well understood. Objective: We aim to define the TME of PTC cases by characterizing the TILs. Design: This is a cross-sectional observational study. Patients: We enrolled 29 PTC (23 having concurrent LT), 14 LT, and 13 hyperplastic nodules with LT (HN) patients from January 2016 to December 2020. Measurements: Immunohistochemical (IHC) expression of CD8, FoxP3, PD-1, and PD-L1 was studied in PTC with LT and compared with HN. PD-1 and PD-L1 expression was correlated at the mRNA level by quantitative real-time PCR. Immunophenotyping of TILs was done in FNAC samples of PTC and LT by flow cytometry. Results: IHC revealed the presence of CD8+ cytotoxic T lymphocytes (CTLs) and FoxP3+ T regulatory cells (Tregs) in 83% and 52% of PTC with LT cases, respectively. Flow cytometric analysis of the PTC samples revealed a significant abundance of CTL compared with Treg and a higher CTL with lower Treg counts compared with LT. On IHC, PD-1 positivity was noted in 56.5% of PTC with LT cases, while intermediate PD-L1 positivity was found in 70% of the cases. There was a significant upregulation of PD-1 mRNA in PTC with LT. A significant correlation was noted with PD-L1 expression with lymph node metastasis and presence of Treg cells. Conclusions: Increased expression of PD-1 and PD-L1 in the TME of PTC may provide a potential molecular mechanism for tumor survival despite the predominance of CTLs, possibly through their inactivation or exhaustion.

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.

Effect of breathing intervention in patients with COVID and healthcare workers.

Background: Regulated breathing facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on patients with COVID remains unclear. We aimed to evaluate the efficacy of two breathing protocols, i.e., short breathing technique (SBT) and long duration breathing technique (LBDT). Methods: Three groups including COVID-positive patients, COVID-recovered patients, and healthcare workers (HCWs) were included in the study and segregated into Yoga and control groups. SBT was administered to COVID-positive patients. Both SBT and LBDT were administered to COVID-recovered patients and HCWs. A total of 18 biochemical parameters, a 6-min walk test (6MWT), and a 1-min sit-stand test (1MSST) were assessed on 0th, 7th, and 15th days, where biochemical parameters were the primary outcome. Pre-post estimation of neuropsychological parameters (nine questionnaires) and heart rate variability (HRV) were carried out. The paired t-test or Wilcoxon rank test was applied for pre-post comparison and the Student's t-test or Mann-Whitney U test was used for group comparison. Repeated measures test was applied for data recorded at three time points. Results: A significant elevation in white blood cell (WBC) count was observed in COVID-positive intervention (p < 0.001) and control groups (p = 0.003), indicating no role of intervention on change in WBC number. WBC count (p = 0.002) and D-dimer (p = 0.002) significantly decreased in the COVID-recovered intervention group. D-dimer was also reduced in HCWs practicing Yogic breathing as compared to controls (p = 0.01). D-dimer was the primary outcome, which remained below 0.50 µg/ml (a cutoff value to define severity) in the COVID-positive yoga group (CYG) and decreased in the COVID-recovered yoga group (RYG) and the HCW yoga group (HYG) after intervention. A 6-min walk test (6MWT) showed an increase in distance covered among the COVID-positive patients (p = 0.01) and HCWs (p = 0.002) after intervention. The high-frequency power (p = 0.01) was found to be reduced in the COVID-positive intervention group. No significant change in neuropsychological parameters was observed. Conclusion: Yogic breathing lowered D-dimer, which is helpful in reducing thrombosis and venous thromboembolism in patients with COVID-19 besides lowering the chances of vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. The breathing intervention improved exercise capacity in mild to moderate cases of COVID-19. Further studies can show if such breathing techniques can influence immunity-related genes, as reported recently in a study. We suggest that Yogic breathing may be considered an integrative approach for the management of patients with COVID. Trial registration: http://ctri.nic.in/Clinicaltrials/login.php, identifier: CTRI/2020/10/028195.