Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with limited diagnostic and prognostic markers. Neutrophil extracellular traps (NETs) have recently been implicated in cancer progression, but their clinical relevance in PDAC remains underexplored. In this preliminary study, we investigated NET levels in both peripheral blood and tumor tissues from PDAC patients (n = 30) and explored their associations with clinicopathological features. We quantified NETs using a multiparametric approach that included immunohistochemistry, immunofluorescence, qRT-PCR, ELISA, and flow cytometry. Plasma NET-associated DNA was measured using the Quant-iT PicoGreen assay. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic potential of NETs. We found NET levels were significantly elevated in both tumor tissue and the circulation of PDAC patients compared with healthy controls. The levels of NETs were strikingly higher in patients with advanced tumor stages and grades. Patients' NETs showed a typical morphology with enlarged nuclei, thread-like DNA fibres, and MPO-positive granules, which was confirmed by immunofluorescence analysis. The ROC analysis demonstrated that NETs displayed promising diagnostic performance (AUC = 0.852) compared to widely used conventional markers CEA and CA19-9 within the study cohort. In conclusion, our findings provide preliminary evidence that increased NETosis is associated with PDAC progression and highlight its potential as a diagnostic biomarker. Larger, independent studies are needed to validate these observations and to determine the clinical relevance of NET-associated markers in PDAC.

Assessment of disease activity in acromegaly is mainly based on growth hormone and insulin-like growth factor 1. However, discordance between these markers is common and may make follow-up difficult. This study evaluated soluble alpha-Klotho as an adjunct biomarker of biochemical disease activity in acromegaly. This case-control study included 80 patients with acromegaly and 80 controls. Patients were categorized as controlled, discordant, uncontrolled, or active disease. Serum soluble alpha-Klotho was measured by sandwich enzyme-linked immunosorbent assay and analyzed across groups, disease-status categories, and clinical-biochemical variables. Receiver operating characteristic analysis and nested models assessed its diagnostic and incremental value. Alpha-Klotho concentrations were higher in acromegaly than controls [1551.9 (835.0–3158.3) vs. 759.7 (625.0–898.5) pg/mL; P < 0.001] and increased across disease-status categories: controlled treated acromegaly [722.0 (668.4–837.8)], discordant treated acromegaly [1426.9 (1119.0–1499.9)], uncontrolled treated acromegaly [2980.0 (2585.0–3650.0)], and newly diagnosed active acromegaly [3820.0 (2460.0–4620.0) pg/mL; overall P < 0.001]. Alpha-Klotho correlated with growth hormone and insulin-like growth factor 1 and identified active/uncontrolled disease with an area under the curve of 0.983. Its addition to growth hormone, insulin-like growth factor 1, age, sex, and body mass index improved discrimination from 0.947 to 0.986. Alpha-Klotho ≥ 1579.8 pg/mL was independently associated with active/uncontrolled disease. Soluble alpha-Klotho may serve as an adjunct marker of current biochemical activity in acromegaly, particularly for identifying uncontrolled treated or newly diagnosed active disease. It may aid selected cases with difficult biochemical interpretation, but should be used alongside GH, IGF-1, clinical assessment, and pituitary imaging, not as a replacement test.

INTRODUCTION:Primary hyperparathyroidism (PHPT) is a systemic endocrine disorder characterized by elevated PTH levels and hypercalcemia. Gene-specific epigenetic modifications like histone methylation play a pivotal role in PHPT by altering expression of parathyroid-specific genes. However, global histone modifications in parathyroid tumors and their implications for tumor behavior remain underexplored. EXPERIMENTAL DESIGN:We performed comparative histone modification profiling in blood and tissue samples from sporadic parathyroid adenomas (PA; n = 30), atypical parathyroid tumors (APT; n = 05), and parathyroid carcinomas (PC; n = 05) along with controls using histone H3 multiplex immunoassay. Significantly dysregulated modifications were validated by Western blotting (WB), and expression data was correlated with clinicopathological features. We performed pathway enrichment analysis to elucidate molecular pathways potentially linked to histone H3 modifications in parathyroid tumorigenesis. RESULTS:We observed dynamic alterations in histone H3 modifications of lysine (K) residues across parathyroid tumor phenotypes in blood and tissue samples. A reduction in H3K4 and H3K36 trimethylation (<60%) and an increase in H3K27 trimethylation and H3K9 monomethylation (>130%) compared to controls was observed. WB confirmed lower H3K4me3 (0.5 ± 0.4 vs 4.4 ± 0.7, P = .02; 0.4 ± 0.2 vs 4.4 ± 0.7, P = .004) and H3K36me3 (0.4 ± 0.2 vs 1.0 ± 0.3, P = .03; 0.2 ± 0.1 vs 1.0 ± 0.3, P = .02) in APT and PC than controls and higher H3K27me3 expression in PA (2.9 ± 1.2 vs 1.1 ± 0.21, P = .04), APT (4.2 ± 2.9 vs 1.1 ± 0.21, P = .007), and PC (6.9 ± 3.1 vs 1.1 ± 0.21, P = .0002) relative to controls. Pathway enrichment analysis identified molecular pathways, including calcium signaling, Wnt, and Hippo signaling, associated with histone H3 modifications. CONCLUSION:Increased expression of repressive H3K27me3 in blood and tissue samples, while decreased H3K4me3 and H3K36me3, suggest a shift toward transcriptional repression. Identifying their functional mechanisms may facilitate the discovery of novel insights for therapeutic targeting in parathyroid tumors.

The current diagnostic methods for syndrome of inappropriate antidiuresis (SIAD) and cerebral salt wasting (CSW), are imprecise. Gold standard radioisotope methodologies are currently confined to research settings. Therefore, this study evaluated whether the change in copeptin levels could be an early diagnostic tool. A study was conducted on hyponatremic (≤ 130 meq/L) children. Subjects with endocrine disorders, systemic diseases, diarrhea, and shock were excluded. At baseline, copeptin and fractional excretion of uric acid (FEUA) were measured. Subjects then received maintenance 0.9

Tumor-infiltrating neutrophils (TINs) have been observed to be linked with poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). In the inflammation and oxidative stress-rich tumor microenvironment, neutrophils are likely to undergo neutrophil extracellular traps (NETs) formation which have unique capability of shielding the tumor cells from anti-tumor immune response and facilitate tumor progression. However, the extent of NET infiltration in PDAC and the specific mechanisms by which NETs contribute to tumorigenesis remain unclear. This study aims to investigate NETs infiltration in PDAC and their impact on PDAC progression. Tumor-infiltrating neutrophils (CD15) and NETs specific markers (citrullinated histone H3, Myeloperoxidase) in the tumor tissue and blood of 15 PDAC patients and 15 healthy volunteers were determined by flow cytometry, gene expression and immunofluorescence. NETs were cocultured with Panc1 cells to assess their effect on tumor growth and behavior through various tumorigenic assays (MTT, colony formation assay, scratch assay). The gene expression analysis was done for epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) modulation, stemness and dormant cell markers through qRT-PCR and further confirmation at protein level by western blot. In both blood and tissue samples of PDAC patients, relative percentage of NETs were markedly increased and the levels of citrullinated histone is positively correlated with higher tumor stage & grade. Moreover, circulating NETs shows a significant linear positive correlation with local pancreatic tumor NETs, indicates an association between NETs infiltration and disease severity. In vitro, NETs increased tumor migration and induced a more aggressive mesenchymal phenotype. They promoted tumor progression and invasion by downregulating epithelial markers (E-cadherin, ZO-1) and upregulating mesenchymal markers (N-cadherin, Vimentin, Snail, Twist, Zeb1, IL8, TGFβ) as well ECM-modulating markers (αSMA, Desmin, MMP, TIMP). Additionally, NETs contributed to tumor relapse by awakening dormant cancer cells (Dec2, p21, p27, p38) and increasing the expression of proliferative markers (Ki67, ERK, Bcl2) along with stemness markers (Sox2, Oct4, Nanog). NETs contribute to a pro-metastatic cancer phenotype by activating EMT and reactivating dormant cancer cells. Therefore, NETs may serve as independent diagnostic biomarker and a potential therapeutic target in PDAC. Sakshi Bansal, Anjali Aggarwal, Vinit Sharma, Rajesh Gupta, Harjeet Singh, Naresh Sachdeva, Alka Bhatia. Neutrophil extracellular traps drive the tumorigenic potential in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3447.

AIM:Persons who inject drugs (PWID) are prone to bloodstream infections, but diagnosis is often delayed. This study evaluated the utility of admission serum procalcitonin for early detection of bacteremia. METHODS:A total of 131 adult male PWID admitted with suspected sepsis were prospectively enrolled. RESULTS:Bacteremia was confirmed in 52 (39.7%) cases, primarily due to Staphylococcus aureus and S. haemolyticus. Infective endocarditis was the leading diagnosis among bacteremic patients. Procalcitonin levels ≥0.51 ng/mL demonstrated high sensitivity (88.5%) and negative predictive value (82.9%), but low specificity (36.7%), resulting in limited diagnostic utility (area under the curve [AUC] 0.613). C-reactive protein (AUC 0.680) and serum albumin (AUC 0.723) outperformed procalcitonin. In-hospital mortality was 35.1%. CONCLUSION:Admission procalcitonin has limited diagnostic value for detecting bacteremia in PWID.

Common comorbidities like type 2 diabetes mellitus and obesity along with their manifestations are linked to COVID-19 severity. Understanding perturbation in biochemical and endocrine parameters in these patients could help us define treatment modalities/guidelines for managing long COVID. We attempted to comprehensively analyse various such markers to find their plausible influence on severity/mortality. A total of 120 COVID-19 patients (mild and severe) were enrolled comprising four subgroups: COVID-19 only, COVID-19 with T2DM, COVID-19 with obesity and COVID-19 with T2DM and Obesity. Comprehensive biochemical and endocrine evaluation was performed using the peripheral blood samples. Only CRP and LDH were found to correlate to disease severity and clinically relevant. Severe patients from three subgroups (except COVID-19 with T2DM) had significantly increased levels of CRP, ALT, AST, DB and Mg, while levels of cholesterol, T3 and LDL were found to be lower. HbA1c levels were higher in severe patients of non-diabetic subgroups. This study provides a detailed informative analysis which could be referred towards understanding the dynamics of infection-associated complications. COVID-19-associated immune aberrations along with existing comorbidities could differentially influence biochemical and endocrine profiles in both mild and severe patients with and without diabetes and/or obesity.

OBJECTIVES:We aimed to determine the effect of high-dose cholecalciferol supplementation starting soon after diagnosis on residual β-cell function (RBCF) and partial remission (PR) rates in children with type 1 diabetes (T1D). METHODS:A prospective, randomized, open-label study was conducted in children aged 2-12 years with newly-diagnosed T1D. Cases received additional cholecalciferol (60,000 IU every fortnight) for six months, while age-matched controls received standard care. Primary outcome variables included change in RBCF (measured by stimulated C-peptide, SCP) and the proportion of patients with PR (insulin dose-adjusted HbA1c, IDAA1c ≤9.0 %) at study endpoint. Secondary outcomes included change in mean daily insulin dose (DID) and mean HbA1c levels. RESULTS:The mean serum vitamin D concentrations achieved in cases (n=32, mean age 7.2 ± 2.8 years) were higher at 6 months (44.91 ± 5.36 vs. 24.87 ± 4.10 ng/mL, p<0.001). Compared to controls (n=31, mean age 6.6 ± 2.5 years), children receiving vitamin D exhibited a slower decline in SCP levels (mean decrease -0.28 ± 0.10 vs. -0.50 ± 0.10 ng/mL, p<0.001). The mean decrease in IDAA1c was higher in cases (-11.1 ± 0.56 %) compared to controls (-10.1 ± 0.52 %), but the difference in mean decrease (-1.1 ± 0.61) did not attain statistical significance (p=0.08). At 6 months, PR rates were significantly higher in cases compared to controls (19, 59.4 % vs. 6, 19.4 %, p<0.001). Regression analysis revealed baseline SCP as strong predictor of SCP at the study endpoint (r=0.92, p<0.001). CONCLUSIONS:High-dose vitamin D supplementation may preserve RBCF and prolong PR in children with newly diagnosed T1D. Large-scale randomized controlled trials are warranted.

INTRODUCTION:Despite the success of vaccination, isolated cases of COVID-19 infection are being reported in the vulnerable subjects worldwide. Given that individuals with type-2 diabetes (T2D) often exhibit immune dysregulation, this study aimed to characterize SARS-CoV-2-specific immunity following ChAdOx1 nCoV-19 vaccination in subjects with T2D. METHODS:We recruited 55 T2D and 60 healthy control (HC) subjects and monitored their immunological parameters at baseline, 3rd, 6th, and 12th month post-ChAdOx1 nCoV-19 vaccination. The frequency of SARS-CoV-2 epitope-specific CD8+ T cells were determined using MHC-I dextramers. The SARS-CoV-2 specific recall responses were assessed by lymphocyte proliferation, intracellular (TNF-α, IFN-γ) and extracellular (IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-β) cytokine estimation following in-vitro stimulation with SARS-CoV-2 S-protein peptide pool (SP). The anti-S antibody titers and the frequency of memory B cells (CD19+ CD27+), plasmablasts (CD19+ CD27hiCD38hi), and plasma cells (CD38hi CD138+) were also determined. RESULTS:Following vaccination, the incidence of COVID-19 disease was significantly higher in T2D individuals, suggesting an increased rate of breakthrough infections. The T2D cohort also exhibited lower frequency of SARS-CoV-2-specific peripheral CD8+ T cells and demonstrated diminished recall responses, as evidenced by reduced in-vitro lymphocyte proliferation. During breakthrough COVID-19 disease, systemic levels of IFN-γ were elevated in T2D subjects, whereas higher IL-10 levels were observed only in HC. Upon SP stimulation, a greater proportion of CD8+ and CD4+ T cells from HC expressed IFN-γ and TNF-α, indicating a more robust antiviral cell-mediated immune response. Additionally, B cell immunophenotyping revealed a reduced frequency of memory B cells in T2D. CONCLUSION:The data indicate that individuals with T2D exhibit impaired vaccine-induced SARS-CoV-2-specific immunological memory, in contrast to HC, who demonstrate a well-regulated balance between pro- and anti-inflammatory responses.

Objectives: The prevalence and predisposing factors to metabolic dysfunction-associated fatty liver disease (MAFLD) in children with type 1 Diabetes (T1D) living in developing countries are unknown. Methods: A cross-sectional study was conducted in children with T1D. The presence of liver fat and tissue stiffness were assessed by ultrasonography and shear-wave elastography (SWE), respectively. The SWE values were correlated to body mass index (BMI), glycemic control, disease duration, and gamma-glutamyl transferase (GGT). Healthy non-obese children (n=36) were recruited as controls. Results: One hundred children with T1D were grouped (Group A-C) according to the disease duration (<5, 5-10, and >10 years, respectively). The mean diabetes duration and glycated hemoglobin were 5.9 +/- 4.0 years and 8.2 +/- 0.55 %, respectively. The mean SWE values were significantly higher in the patient groups compared to controls (5.07 +/- 0.67, 5.27 +/- 0.65, 5.16 +/- 0.50, vs. 4.80 +/- 0.82 kPa, p-value 0.006). The liver stiffness based on SWE showed a positive but weak relationship with BMI, diabetes duration, glycemic control, and GGT levels. A significantly higher number of children with T1D had MAFLD [9(20 %), 7(24.1 %), 7(26.9 %), vs. 1(3 %), p-value <0.001] based on ultrasonography. Conclusions: Children with T1D showed higher liver stiffness values than controls. A weakly positive relationship of liver stiffness was observed with BMI, duration of diabetes, glycemic control, and serum GGT. Approximately one-fourth of children with diabetes showed sonographic evidence of hepatic steatosis. Larger studies are needed to ascertain the effects of obesity, diabetes duration, and metabolic control on the prevalence and progression of MAFLD in children with T1D.

ObjectiveTo compare early hydrocortisone (initiated along with vasoactive therapy) vs. placebo for all-cause mortality within next 14 days among neonates with fluid-refractory shock.Study designNeonates with fluid-refractory shock were randomly assigned to receive hydrocortisone or saline placebo alongside vasoactive drugs. If they developed catecholamine-resistant shock, the study drug was replaced with open-label hydrocortisone.ResultEighty-four neonates were randomized (early hydrocortisone=43 and placebo=41). Median gestational age of our cohort (n = 84) was 30.3 weeks [interquartile range (IQR): 27.7, 32.5] and median birth weight was 1148 grams (IQR: 860, 1419). The 14-day all-cause mortality was comparable between early hydrocortisone and placebo groups [OR 0.53 (95% CI 0.19, 1.52)]. Both groups had similar duration of vasoactive drugs and vasoactive-inotrope scores, incidence of adverse effects of hydrocortisone and incidence of medium-term complications.ConclusionWe did not observe a significant reduction in 14-day mortality with early hydrocortisone compared to placebo in fluid-refractory neonatal shock.

BACKGROUND:Type 1 diabetes (T1D) involves selective destruction of pancreatic beta (β) cells, mainly by infiltrating CD8+ T cells. These CD8+ T cells also express immune-checkpoint molecules (ICMs) that can be targeted by immune-checkpoint ligands (ICLs) or β cell-specific Tregs. Here, we combined both approaches to suppress autoimmune responses in T1D. METHODS:We first performed profiling of various ICMs on peripheral CD8+ T cells in 40 recent-onset T1D and 20 age-matched healthy subjects by flow cytometry. Tregs were isolated from the same subjects and stimulated with preproinsulin (PPI) in vitro. Exosomes were isolated from PPI-specific Tregs and characterized by western blotting, transmission electron microscopy, zeta potential, and particle size analysis. Based on ICM profile, ICLs corresponding to the 3 most abundant ICMs (PD-1, TIGIT, BTLA) expressed on the peripheral CD8+ T cells were used for loading exosomes. The efficacy of ICL-loaded exosomes (PPI-T-EXOL) was further assessed by various in vitro and in vivo approaches. RESULTS:The PPI-T-EXOL inhibited the proliferation of autologous CD8+ and CD4+ Teff cells. The PPI-T-EXOL and PPI-Tregs infused with PPI-T-EXOL significantly downregulated the activation and cytotoxic potential of autologous PPI-pulsed CD8+ T cells. These Tregs also reduced CD8+ T cell-mediated apoptosis of human 1.1B4 β-cell line. In STZ-induced diabetic C57BL/6 mice, the mice-specific ICL-loaded exosomes delayed the onset of hyperglycemia, particularly when administered before the onset of diabetes and prolonged their survival by inhibiting perivascular lymphocytic intra-islet infiltration. CONCLUSIONS:ICL-loaded PPI-Treg-derived exosomes can suppress β cell-specific T cell responses, offering a promising therapeutic intervention in T1D.

Introduction:Appropriate gonadotropin therapy regimen for the induction of spermatogenesis in congenital Hypogonadotropic Hypogonadism (HH) patients is a matter of debate. Pre-treatment with hCG is discouraged, while the rationale for FSH pre-treatment is that it mimics minipuberty, thereby being expected to be better than upfront combined hCG and FSH therapy. Methods:A prospective RCT was conducted in the Department of Endocrinology of a tertiary centre. 24 azoospermic males between 17y and 40y of age with congenital HH were randomized into two groups. Group A (n = 12) received upfront combined hCG and FSH, while group B (n = 12) was given pre-treatment with FSH for 3 months, before addition of hCG. Results:Patients were followed up for a maximum duration of 18 months. Overall success rate was 91.3% (21/23). In group A, 100% (12/12) responded to treatment compared with 81.8% (9/11) in group B, with significantly lesser median (IQR) time to spermatogenesis of 10.5 (9-12) months in group A, compared to 15 (13.5-16.5) months in group B (P = 0.007). Maximum sperm concentration [median (IQR)] attained in group A and B was 30 (15.5-47) million/mL and 20 (7.5-34.5) million/mL, respectively (P = 0.292). Sonographic bi-testicular volume (median) increased to 8.05 (7.13-10.57) mL in group A and 9.2 (5.45-14) mL in group B. Conclusion:Both FSH pre-treatment and upfront combined hCG and FSH have a favourable outcome in initiating spermatogenesis in congenital HH, with the time to initiation of spermatogenesis favouring combined treatment.

Background: Prospective studies identifying immunological parameters that can predict clinical relapse in pemphigus are scarce. Objective: To periodically assess immunological parameters in patients with pemphigus vulgaris and foliaceous in remission to understand immunological events preceding clinical relapse. Methods: A total of 105 patients were included. Baseline assessment included direct immunofluorescence (DIF), serum IgG against desmoglein (Dsg) 1, IgG, IgG1, and IgG4 against Dsg 3, IgG against the extracellular domains 1 and 2 of Dsg 3, IgG against muscarinic (M3)-AchR, and peripheral CD19+CD27+ memory B cells/plasma cells, repeated every 3 months for up to 12 months or until clinical relapse. DIF was repeated at month 12 and on relapse. Results: About 29 of 105 patients (28%) experienced a relapse. Longer duration of clinical remission, presence of pruritus and positive anti-Dsg1 at baseline correlated with higher relapse rates. Compared with the visit immediately preceding relapse, a significantly increased number of patients with positive anti-Dsg1 (38% vs 31.1%, P = .01), antiDsg3 (51.7% vs 41.4%, P= .01) and IgG positivity by DIF (85.7% vs 25%, P<.001) was observed at the time of relapse. Conclusion: Regular monitoring of anti-Dsg 1 and anti-Dsg 3 serum levels and DIF positivity during the course of the disease in remission may predict relapse.

To study the effect of two doses of BCG vaccination on immune-regulatory markers and glycemic control in patients with type 1 diabetes (T1DM). In this single-centre, double-blinded, randomised, placebo-controlled pilot trial, children with new-onset T1DM (diagnosed within the last 6 months) were included and were randomised 1:1 into BCG and placebo groups, with 20 children in each group. Two doses of 0.1-mL BCG vaccine or 0.1 mL of normal saline was administered intradermally 1 month apart in the BCG group and placebo group, respectively. The primary outcome parameters included changes in regulatory T cell (T-regs) percentage, changes in pancreatic autoantibody titres and serum IL-10, IL-17, and TNF-alpha cytokine levels. The secondary outcome parameters included changes in various glycemic control parameters. At the end of 6 months, no significant differences were observed in Treg percentages, cytokine levels, and autoantibody titres between the BCG and placebo groups. We observed a reduction of HbA1c (p = 0.421) and a lesser fall of C-peptide (p = 0.496) values in the BCG group. The mean fasting, random blood sugar, and median total/basal/bolus insulin dose did not vary significantly between the two groups at 6 months. BCG administration did not significantly improve immune-regulatory markers and glycemic control parameters among children with new-onset T1DM who have been vaccinated at birth. However, there was a trend towards improvement of glycemic parameters in BCG group.

The INDIIGo study aimed to establish normative data for serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in adult Indian males, addressing the paucity of data for the South East Asian population. This cross-sectional study included 1271 healthy males aged 20 to 65.9 years from Chandigarh, India, with measurements obtained using the Roche Elecsys electrochemiluminescence immunoassay (ECLIA). Age-specific normative centile curves were generated using the LMS (Lambda, Mu, Sigma) method. Serum IGF-1 levels declined by 30.1 ng/ml per decade (95% CI - 34.9 to - 25.2; p < 0.001) and were negatively associated with lower socioeconomic status (- 5.8 ng/ml per class; p = 0.002), ALT (- 0.6 ng/ml per unit; p < 0.001), and HbA1c (- 8.2 ng/ml per category; p = 0.04). Positive correlations were observed with serum T4 (+ 4.5 ng/ml per unit; p < 0.001) and serum albumin (+ 18.0 ng/ml per g/dL; p = 0.009). IGFBP-3 levels decreased by 447.8 ng/ml per decade (95% CI - 547.6 to - 348.1; p < 0.001), with a significant positive association with serum T4 (+ 60.8 ng/ml per unit; p = 0.025). This study provides age-specific normative data for IGF-1 and IGFBP-3 in Indian males and identifies key factors influencing these biomarkers.

Despite the multiple advantages of 25-hydroxyvitamin D (calcifediol or 25(OH)D) compared to cholecalciferol, it is used sparingly. This study was planned to assess the safety and efficacy of supplementing daily 25 µg of calcifediol capsules vis-a-vis 100 µg (4000 IU) of cholecalciferol sachets in apparently healthy individuals with vitamin D deficiency in Chandigarh, India (latitude 30.7° North, 76.8° East). It was a prospective, interventional study to evaluate the effects of calcifediol vis-a-vis cholecalciferol. Following initial screening of 70 subjects in each group, 62 were included in the calcifediol and 41 in the cholecalciferol group. Forty-six from calcifediol and 37 from cholecalciferol group completed the 6-month follow up. There was a significant increase in serum 25(OH)D (355% in cholecalciferol & 574% in calcifediol groups, respectively, p < 0.001) and 1,25 (OH)2D (p < 0.001) with a marked decrease in iPTH (p < 0.001) and ALP (p = 0.016) in both groups. Though serum ALP decreased significantly more in the calcifediol group than the cholecalciferol group, no appreciable difference in other biochemical parameters was noted between the groups. No episodes of hypercalcaemia or incidence of new renal stone disease were observed during follow-up. However, hypercalciuria (spot urine calcium creatinine > 0.2 mg/mg) was noted in 8/46 individuals in the calcifediol group and 5/37 individuals in the cholecalciferol group at final visit with no significant difference between two groups. This study establishes the efficacy and safety of correcting vitamin D deficiency with daily 25 µg calcifediol capsules as an alternative to 4000 IU (100 µg) cholecalciferol sachets.

Background:Rituximab-mediated B-cell depletion in pemphigus patients is majorly caused by antibody-dependent cellular cytotoxicity. This is mediated by Fcγ receptors on immune cells, particularly FcγRIIIa (CD16) on natural killer (NK) cells. This study investigates the impact of FcγRIII expression on response to rituximab in pemphigus patients. Patients and Methods:A cross-sectional study was carried out on 85 pemphigus patients who had been treated with rituximab using a rheumatoid arthritis protocol. Patients who achieved complete remission within 4.5 months were arbitrarily defined as responders. CD16 expression on NK cells, NK-T cells, and monocytes, as well as FcγRIIIa-158V/F polymorphism, were assessed using flow cytometry and genetic assays, respectively. Results:CD16 expression on NK cells and NK-T cells was higher in responders than in resistant patients but did not reach statistical significance. A significant negative correlation was observed between NK-T cell percentage and time to remission (P < 0.001), suggesting NK-T cell percentage as a possible marker for prediction of time to remission. Distribution of FcγRIIIa genotypes (V/V, V/F, F/F) did not significantly differ between responders and resistant patients (P = 0.574). A statistically non-significant trend suggested that FF homozygotes may have a slightly worse survival outcome in achieving remission compared to FV/VV genotypes, with a hazard ratio of 1.255 (95% CI: 0.6112-2.577). Limitations:Small, single-center sample, potential selection bias, and lack of long-term follow-up or functional assays. Conclusion:This study underscores the potential influence of CD16 expression and FcγRIIIa polymorphism in response to rituximab in pemphigus patients, emphasizing the need for further research to establish definitive relationships for personalized treatment strategies.