A double-blinded randomised control study to compare the effectiveness and safety of intralesional vitamin D3 with intralesional triamcinolone and its correlation with tissue expression of vitamin D receptors in patients with keloid.

Intralesional steroids commonly used for keloid treatment have adverse effects like cutaneous atrophy and telangiectasias. Safer and more effective therapies are needed. Preliminary studies suggest intralesional vitamin D as a potential alternative treatment. The aim of this study was to compare efficacy and safety of intralesional vitamin D with triamcinolone for keloids, and correlate tissue expression of vitamin D receptors (VDRs) with treatment outcomes. Sixty patients were randomly assigned to two groups: Group A (intralesional vitamin D) and Group B (intralesional triamcinolone). Four injections were given at 4-week intervals, with an 8-week follow-up. Biopsies were taken pre- and post-treatment to examine VDR expression levels and treatment response correlation. The primary outcome of interest was the proportion of patients achieving a 50% reduction in Vancouver Scar Scale (VSS). Secondary outcomes included incidence of adverse effects, and changes in VDR expression before and after treatment. Baseline VSS scores were 9.73 ± 1.01 (vitamin D group) and 10.13 ± 1.07 (triamcinolone group). After treatment, mean VSS decreased to 5.17 ± 0.59 (vitamin D group, p < 0.001) and 4.77 ± 0.77 (triamcinolone group, p < 0.001), with significantly better response in latter (p = 0.03). More than 50% reduction in VSS score was higher in the triamcinolone group (76.7% vs. 50%, p = 0.032). No recurrences were noted during the 8-week follow-up. Hypopigmentation (80% vs. 36.7%, p < 0.001) and atrophy (73.3% vs. 40%, p = 0.009) were more common in the triamcinolone group. No significant difference in pre- and post-treatment VDR receptor expression was observed in either group. Both triamcinolone acetonide and vitamin D were effective for keloids. Triamcinolone was more efficacious, whereas vitamin D was safer, suggesting it as a viable alternative for keloid management.

Effect of Combined Low Dose Human Gonadotropic Hormone, Follicle Stimulating Hormone, and Testosterone Therapy (LFT Regimen) Versus Conventional High Dose Human Gonadotropic Hormone and Follicle Stimulating Hormone on Spermatogenesis and Biomarkers in Men With Hypogonadotropic Hypogonadism.

OBJECTIVE: In male congenital hypogonadotropic hypogonadism (CHH), it was observed that lower dose human gonadotropic hormone (hCG) can maintain normal intratesticular testosterone levels. We propose this study to compare the low-dose hCG, follicle stimulating hormone (FSH), and Testosterone (T) [LFT Regimen] to conventional treatment to induce virilization and fertility. DESIGN: This open-label randomized pilot study was conducted from June 2020 to December 2021. SUBJECTS AND OUTCOME MEASURES: CHH were randomly assigned to either the LFT regimen (Group A)-low-dose hCG (500U thrice per week), FSH (150U thrice per week), and T(100 mg biweekly) or conventional therapy(GroupB) with high hCG dose(2000U thrice per week) and the same FSH dose. The hCG dosage was titrated to reduce anti-mullerian hormone (AMH) by 50% and normalization of plasma T in groups A and B, respectively. The primary objective was to compare the percentage of individuals who achieved spermatogenesis between the two groups. RESULTS: Out of 30 patients, 23 (76·7%) subjects achieved spermatogenesis, and the median time was 12 (9-14·9) months. There was no difference in achieving spermatogenesis between the two groups (64·3% vs 7·5%,P = 0·204), and even the median time for spermatogenesis was similar (15months vs 12months,P = 0·248). Both groups had nonsignificant median plasma AMH at spermatogenesis, [6·6 ng/ml (3·3-9·76) vs4·41 ng/ml (2·3-6·47), P = 0·298]. Similarly, the median plasma Inhibin B at spermatogenesis between groups were comparable [152·4 pg/ml (101·7-198·0) vs49·1 pg/ml (128·7-237·3), P = 0·488]. CONCLUSIONS: A reasonable approach to induce fertility in male CHH is to initiate combination therapy using FSH, low-dose hCG targeting AMH <6·9 ng/ml, along with T to achieve normal range. Monitoring AMH could serve as a proxy indicator of spermatogenesis.

Impact of BMI on serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with calcifediol supplementation in young adults: a longitudinal study.

BACKGROUND: High body mass index (BMI) is a risk factor for vitamin D deficiency. The rise in serum 25-hydroxyvitamin D [25(OH)D] concentrations following cholecalciferol supplementation is suboptimal, owing to adipose tissue sequestration and/or volumetric dilution. Calcifediol is a proven potent oral alternative for vitamin D supplementation, but whether BMI adversely affects its efficacy in raising 25(OH)D concentrations, is not well known. MATERIAL AND METHODS: Adults with serum concentrations of 25(OH)D < 30 ng/mL were recruited and stratified as normal, overweight, or obese using WHO criteria. Baseline evaluation included 25(OH)D, parathyroid hormone (PTH), and total 1,25-dihydroxyvitamin D [1,25(OH)2D] based on BMI category (n = 883). A subset of participants was supplemented with 50 µg calcifediol (n = 193) and assessed for the rise in serum concentrations of 25(OH)D at 3- and 6-months following supplementation. RESULTS: Participants were stratified as obese (11.2%), overweight (32.1%), or normal weight (56.7%). There were no significant baseline differences in serum concentrations of 25(OH)D among the groups (13.1 ± 6.4 vs 12.8 ± 6.8 vs 11.6 ± 6.6 ng/mL, p = 0.62). Similarly, PTH or 1,25(OH)2D concentrations were not different among the groups. On follow-up, 25(OH)D concentrations increased in all three groups at 3 and 6 months from baseline. The increase in 25(OH)D was 74.4 ng/mL (IQR 35.3-115.3) in obese, followed by overweight 62.2 ng/mL (18.1-98.7) and normal weight groups 47.1 ng/mL (17.5-89.7) at 3 months. 1,25(OH)2D also increased in all groups, without any significant intergroup differences (p > 0.05). CONCLUSION: BMI does not impede the rise in 25(OH)D concentrations following supplementation with calcifediol in young adults with vitamin D deficiency.

Calcifediol boosts efficacy of ChAdOx1 nCoV-19 vaccine by upregulating genes promoting memory T cell responses.

The ChAdOx1 nCoV-19 (COVISHIELD) vaccine has emerged as a pivotal tool in the global fight against the COVID-19 pandemic. In our previous study eligible subjects were supplemented with calcifediol, a direct precursor to the biologically active form of vitamin D, calcitriol with an objective to enhance the immunogenicity of the COVISHIELD vaccine. Herein we investigated the effects of calcifediol supplementation on gene expression profiles in individuals who received the COVISHIELD vaccine. Peripheral blood mononuclear cells were isolated from vaccinated individuals with and without calcifediol supplementation at baseline, 3rd and 6th month, and the gene expression profiles were analyzed using high-throughput sequencing. The results revealed distinct patterns of gene expression associated with calcifediol supplementation, suggesting potential molecular mechanisms underlying the beneficial effects of calcifediol in improving the efficacy of COVISHIELD vaccine via augmentation of T cell activation, proliferation and T cell memory responses. Additionally, there was upregulation of NOD like receptor, JAK/STAT and TGF beta signaling pathways. Calcifediol supplementation in vaccinated individuals also downregulated the pathways related to the Coronavirus disease. Taken together, our findings provide valuable insights into the interplay between vitamin D receptor (VDR) signaling and vaccine-induced immune responses and offer another approach in improving vaccination induced antiviral responses.

Normative data for insulin-like growth factor-1 (IGF-1) in healthy children and adolescents from India.

BACKGROUND: Serum IGF-1 is an important biochemical tool to diagnose and monitor GH-related disorders. However, ethnic-specific Indian data following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage-specific normative data for IGF-1 in healthy Indian children and adolescents. METHODS: A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. RESULTS: We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, peak and higher IGF-1 values. The reference interval (2.5th-97.5th percentile) was broader during peri-pubertal ages, indicating a higher physiological variability. CONCLUSION: This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents.

Basal and FSH-stimulated Inhibin B in Precocious Puberty.

OBJECTIVE: To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B in differentiating premature thelarche from gonadotropin-dependent precocious puberty (GDPP). METHODS: This was a prospective interventional study. Basal and FSH-stimulated inhibin B levels were estimated in girls presenting with thelarche < 8 years age (n = 10), healthy girls with normal pubertal development (pubertal control) (n = 8) and healthy prepubertal girls (prepubertal control) (n = 7). Girls with early puberty were classified as premature thelarche or GDPP based on GnRH agonist stimulation test. RESULTS: Median (IQR) basal inhibin B levels (pg/mL) in premature thelarche was 5.42 (2.91, 30.58) and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) (P = 0.043). Median (IQR) basal inhibin B in GDPP was 64.11 (24.96, 792.45) pg/mL and FSH-stimulated inhibin B was 833.66 (500.11-1266.18) pg/mL (P = 0.043). Basal inhibin B was discriminatory between GDPP and premature thelarche (P = 0.032). Median (IQR) basal inhibin B in prepubertal and pubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively. CONCLUSION: Basal inhibin B is useful in differentiation of premature thelarche from GDPP while the role of FSH-stimulated inhibin B needs to be further explored in large sample size.

Unveiling novel metabolic alterations in postmenopausal osteoporosis and type 2 diabetes mellitus through NMR-based metabolomics: A pioneering approach for identifying early diagnostic markers.

BACKGROUND AND AIMS: Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (1H NMR). MATERIALS AND METHODS: Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using 1H NMR spectroscopy. RESULTS: Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker. CONCLUSION: The 1H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.

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.