Incremental value of magnification and indocyanine green for parathyroid preservation in thyroid surgery.

BACKGROUND: To assess the promise of surgical magnification and of intraoperative indocyanine green (ICG) assisted near-infrared fluorescence (NIRF) in improving parathyroid identification and viability assessment during thyroidectomy. METHODS: Prospective comparative study. Parathyroid gland identification sequentially assessed by naked eye, surgical microscopy, and by NIRF imaging following ICG administration (5 mgIV). Parathyroid perfusion/vitality reassessed end-surgery by ICG-NIRF. RESULTS: An expected total of 104 parathyroid glands were assessed in 35 patients (17 total-thyroidectomy, 18 hemi-thyroidectomy). 54/104 (51.9%) were identified by naked eye, and sequentially greater numbers identified by microscope magnification (n = 61; 58.7%; p = 0.33), and by ICG-NIRF (n = 72; 69.2%; p = 0.01). ICG-NIRF detected additional parathyroid glands in 16/35 patients (45.7%). Confident identification of at least one parathyroid remained unachieved in 5/35 by naked eye, in 4/35 by microscopic magnification, and in no patient by ICG-NIRF. ICG-NIRF indicated end-of-surgery devascularization in 12/72 glands and informed decisions regarding gland implantation. CONCLUSION: Significantly greater parathyroid glands are identified and preserved with surgical magnification and with ICG-NIRF. Both techniques merit routine adoption for thyroidectomy.

Innate differences in the molecular signature of normal inferior & superior human parathyroid glands: potential implications for parathyroid adenoma.

Primary hyperparathyroidism is a common endocrine disorder. Interestingly, the majority (75%) of parathyroid tumors are localized to the inferior parathyroid glands. To date, the reason for this natural bias has not been investigated. We assessed the global gene expression profile of superior and inferior glands obtained from forensic autopsies. The genes with significant differential expression between superior and inferior parathyroids were further assessed by RT-PCR in 19 pairs. As an iterative approach, additional genes with an established role in parathyroid disorders, i.e., CASR, MAFB, PAX9, TBCE, TBX1, VDR, MEN1, CCND1, and CDC73 were also evaluated by RT-PCR in all 19 pairs of superior and inferior parathyroid glands. Seven homeobox genes, namely HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, and one encoding for ALDH1A2 showed a lower expression in the inferior parathyroid glands than in the superior. Conversely, SLC6A1 showed a higher expression in the inferior glands. Of the nine genes with significant differential mRNA expression among superior and inferior glands HOXB9, HOXB4 and IRX1 could be detected by western blotting/mass spectrometry. The study is the first to show the differential expression of nine genes HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, ALDH1A2, and SLC6A1 in inferior versus the superior parathyroid glands. This could have potential implications for the preferential localization of parathyroid tumors to the inferior parathyroid glands as observed in patients with primary hyperparathyroidism.

Effect of calcitriol and calcium on basal ganglia calcification in hypoparathyroidism: experimental models.

Basal ganglia calcification (BGC) is a common complication in hypoparathyroid patients, linked to hyperphosphatemia and altered vitamin-D and calcium homeostasis following conventional therapy. The pathogenesis of BGC in hypoparathyroidism is not clear. Recently, we developed an ex vivo model of BGC using rat-striatal cell culture in 10.0 mmol/L of ß-glycerophosphate (31.8 mg/dL phosphate). However, the effect of 1,25(OH)2 D, calcium, and milder phosphate excess on BGC in hypoparathyroidism is not known. This study describes two modified ex vivo models investigating pathogenesis of BGC in 'drug-naïve' and 'conventionally treated' hypoparathyroid state. The first modification involved striatal cells cultured in low concentration 1,25(OH)2D (16.0 pg/mL), ionized calcium(0.99 mmol/L), hPTH(1-34) (6.0 pg/mL), and 2.68 mmol/L (8.3 mg/dL) of phosphate akin to 'drug-naïve' state for 24 days. In second modification, striatal cells were exposed to 46.0 pg/mL of 1,25(OH)2D, normal ionized calcium of 1.17 mmol/L, and 2.20 mmol/L (6.8 mg/dL) of phosphate akin to 'conventionally treated' state. Striatal cell culture under 'drug-naïve' state showed that even 16.0 pg/mL of 1,25(OH)2D enhanced the calcification. In 'conventionally treated' model, striatal cell calcification was enhanced in 54% cases over 'drug-naïve' state. Calcification in 'conventionally treated' state further increased on increasing phosphate to 8.3 mg/dL, suggesting importance of phosphatemic control in hypoparathyroid patients. Striatal cells in 'drug-naïve' state showed increased mRNA expression of pro-osteogenic Wnt3a, Cd133,Vglut-1-neuronal phosphate-transporters, calcium-ion channel-Trvp2,Alp, and Collagen-1α and decreased expression of Ca-II. These models suggest that in 'drug-naïve' state, 1,25(OH)2D along with moderately elevated phosphate increases the expression of pro-osteogenic molecules to induce BGC. Although normalization of calcium in 'conventionally treated' state increased the expression of Opg, Osterix, Alp, and Cav2, calcification increased only in a subset, akin to variation in progression of BGC in hypoparathyroid patients on conventional therapy.

Coronary artery disease and its vascular associates in patients with chronic nonsurgical hypoparathyroidism.

OBJECTIVE: Patients with chronic hypoparathyroidism (cHypoPT) are prone to intracranial-calcification, cataract and nephrocalcinosis. In this study, we systematically investigated the possibility of increased coronary artery calcification (CAC) and coronary artery disease (CAD) in them. DESIGN: Cross-sectional. PATIENTS AND MEASUREMENTS: Ninety-four nonsurgical cHypoPT (M:F = 50:44; age = 45 ± 15 years) with 18.6 ± 9.3 years of illness were assessed. Those with dyspnoea, angina, syncope, abnormal electrocardiogram, echocardiography or significant CAC underwent coronary angiography or myocardial-perfusion-stress imaging. Their lipid parameters and high-sensitivity C-reactive protein (hsCRP) were compared with age-matched healthy controls (Group A, n = 101). The prevalence of CAC in cHypoPT was compared with that of subjects referred from cardiology-clinics (Group B, n = 148, age = 52 ± 11 years). RESULTS: One of 94 cHypoPT had known CAD. On screening, 17 cHypoPT required evaluation for CAD. Two of 17 had severe coronary stenosis, and 12 showed subclinical CAD. CAC and aortic-valve calcification occurred in 21.5% and 11.8%. Clinical and subclinical CAD, CAC and aortic-valve calcification in cHypoPT ≥50 years of age was 8.1%, 27.0%, 52.8% and 27.8%, respectively. Frequency of age-adjusted CAC was comparable between cHypoPT and control Group B (30.2% vs. 30.7%, p = .93). Elevated hsCRP was higher in cHypoPT than in controls A (52% vs. 32%, p < .01). Factors associated with CAD in cHypoPT were CAC and hypertension. However, CAD and CAC showed no association with long-term calcemic or phosphatemic control and intracranial-calcification in cHypoPT. CONCLUSIONS: Clinical and subclinical CAD was observed in 3.2% and 12.8% of cHypoPT patients. The increased prevalence of CAD, CAC and aortic-valve calcification in cHypoPT above 50 years of age suggested their careful cardiac evaluation during follow-up.

Efficacy of Bacillus Calmette-Guérin (BCG) Vaccination in Reducing the Incidence and Severity of COVID-19 in High-Risk Population (BRIC): a Phase III, Multi-centre, Quadruple-Blind Randomised Control Trial.

INTRODUCTION: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection. METHODS: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol. RESULTS: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection. CONCLUSIONS: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study. CLINICAL TRIALS REGISTRY: Clinical Trials Registry India (CTRI/2020/07/026668).

The Bacillus Calmette­Guérin (BCG) vaccine has been studied previously in several settings, including reducing childhood mortalities due to viral infections and induction of trained immunity and reducing upper respiratory tract infections and pneumonia in older adults. This multi-centre trial has tried to evaluate the efficacy of BCG revaccination in reducing the incidence and severity of COVID-19 infections in adults between 18 and 60 years of age belonging to the high-risk group owing to the presence of comorbidities including diabetes, chronic kidney disease, chronic liver disease and chronic lung diseases. A single dose of BCG vaccine produced significantly high titres of BCG antibodies lasting for six months. While there was no significant reduction in the incidence of COVID-19 infection, there was an 8.4% reduction in the incidence of symptomatic COVID-19 disease at the end of 9 months of follow-up. In addition, there were significantly fewer severe COVID-19 infections requiring hospital stay and oxygen support. However, the overall numbers of severe COVID-19 infections were low. Thus, the study shows that BCG can protect against symptomatic and severe COVID-19 disease. However, it might not reduce the incidence of new infections. The study results are significant for low- and middle-income countries without adequate coverage of primary doses of COVID-19 vaccination, let alone the booster doses. Future studies should evaluate the BCG vaccine's efficacy as a booster compared with routine COVID-19 vaccine boosters.

Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review.

The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. Given the pervasive nature of PTH deficiency across multiple organ systems, a detailed review of the skeletal, renal, neuromuscular, and ocular complications is provided. The burden of illness on affected patients and their caregivers contributes to reduced quality of life and social costs for this chronic endocrinopathy. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Bone Mineral Density, Bone Microarchitecture and Vertebral Fractures in Male Patients with Alcohol Use Disorders.

AIM: To investigate abnormalities in bone mineral density, trabecular bone score and vertebral fractures in male patients with alcohol use disorder to understand the impact on bone health. METHODS: The study subjects included 134 male patients. Controls were 134 age matched healthy males. Assessments were made of the bone mineral density (BMD), trabecular bone score (TBS) and vertebral morphometry (VFA) for vertebral fractures. Biochemical measurements included serum total T4, thyroid stimulating hormone (TSH), parathyroid hormone (PTH) and 25- Hydroxyvitamin D 25(OH) D. RESULTS: The mean BMD at total forearm, proximal forearm (or distal 1/3) and mid forearm was significantly higher in the alcohol use disorders (AUD) group than the controls (P < 0.01). Around 15% of patients with AUD had VFs compared with 9.0% of the healthy controls (P = 0.19). For each kg/m2 gain in body mass index (BMI), lumbar spine and total hip BMD increased by 0.009 and 0.014 g/cm2, respectively. Lumbar and hip BMD decreased by 0.002 and 0.003 g/cm2 per year increase in duration of alcohol used. For every 5 years increase in age of the patients the odds of having VFs increased by 39% (odds ratio 1.393 [95% confidence interval = 1.031-1.881, P = 0.03]). CONCLUSION: The findings of the current study suggest that persons with AUD in third and fourth decades of life, with BMI in normal range and with alcohol use disorder duration of around one decade might have no major alteration in BMD and TBS. Impact of alcohol use in this population was manifest by marginal increase in the prevalence of mild grade of vertebral fractures, mostly in the thoracic region.

Perspective: When the cure might become the malady: the layering of multiple interventions with mandatory micronutrient fortification of foods in India.

When public health programs with single nutrients are perceived to have a poor impact on the target health outcome, the policy response can be to supply more, by layering additional mandatory programs upon the extant programs. However, we argue for extreme caution, because nutrients (like medicines) are beneficial in the right dose, but potentially harmful when ingested in excess. Unnecessary motivations for the reactionary layering of multiple intervention programs emerge from incorrect measurements of the risk of nutrient inadequacy in the population, or incorrect biomarker cutoffs to evaluate the extent of nutrient deficiencies. The financial and social costs of additional layered programs are not trivial when traded off with other vital programs in a resource-poor economy, and when public health ethical dilemmas of autonomy, equity, and stigma are not addressed. An example of this conundrum in India is the perception of stagnancy in the response of the prevalence of anemia to the ongoing pharmacological iron supplementation program. The reaction has been a policy proposal to further increase iron intake through mandatory iron fortification of the rice provided in supplementary feeding programs like the Integrated Child Development Services and the School Mid-Day Meal. This is in addition to the ongoing pharmacological iron supplementation as well as other voluntary iron fortifications, such as those of salt and manufactured food products. However, before supplying more, it is vital to consider why the existing program is apparently not working, along with consideration of the potential for excess intake and related harms. This is relevant globally, particularly for countries contemplating multiple interventions to address micronutrient deficiencies. Supplying more by layering multiple nutrient interventions, instead of doing it right, without thoughtful considerations of social, biological, and ethics frameworks could be counterproductive. The cure, then, might well become the malady.

Comparison of 4DMRI and 4DCT for the preoperative evaluation of patients with primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroid surgery is the standard of care in patients with Primary Hyperparathyroidism (PHPT) which requires accurate preoperative localization. Of all the available imaging modalities, 4DCT is considered the best modality for localization, however it entails the risk of ionizing radiation. To circumvent this 4DMRI was evaluated for parathyroid lesion localization. PURPOSE: To evaluate and compare the accuracy of 4DCT and 4DMRI in the localization of parathyroid Lesions. MATERIALS AND METHODS: In this ethically approved observational diagnostic study, 135 patients (age range: 10-75 years, male: female ratio - 1:2.1) with clinically and biochemically suspected PHPT were recruited. Of these, 56 patients underwent both 4DCT and 4DMRI. Six patients with positive imaging who didn't undergo surgery were excluded. A total of 50 patients with 61 proven parathyroid lesions were included for analysis. 48 patients had surgical and histopathological findings for the confirmation of imaging findings. RESULTS: Both 4DCT and 4DMRI correctly detected 59/61 lesions in 48 patients. There was one false positive and two true negatives. In addition, 2 (3.22 %) lesions which were not detected by 4DCT and 4DMRI were found on surgery. The sensitivity of both 4DCT and 4DMRI was 96.7 %; specificity was 66.6 % and accuracy was 95.2 %. CONCLUSION: 4DMRI and 4DCT had similar accuracy for the detection of parathyroid lesions. However, 4DMRI has the advantage of lack of exposure to ionizing radiation, which can be beneficial in younger patients.

Alfacalcidol vs Calcitriol in the Management of Patient With Hypoparathyroidism: A Randomized Controlled Trial.

CONTEXT: Alfacalcidol and calcitriol are commonly used for managing hypoparathyroidism. Their relative merits have not been systematically assessed. OBJECTIVE: We compared the effect of alfacalcidol and calcitriol on phosphatemic control, hypercalciuria, and associated factors in idiopathic-hypoparathyroidism (IH). DESIGN AND SETTING: Open-label randomized controlled trial, tertiary care center. SUBJECTS AND METHODS: IH patients with optimal calcemic control on alfacalcidol were continued on the same (n = 20) or switched to calcitriol (n = 25) at half of the ongoing alfacalcidol dose. The dose was adjusted during follow-up to maintain serum total calcium between 8.0 and 9.5 mg/dL. Serum calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24-h urine calcium-to-creatinine ratio, and fractional excretion of phosphorus (FEPh) were measured at baseline and 6 months. Plasma intact-FGF23 was measured at final follow-up. RESULT: Patients receiving alfacalcidol and calcitriol had comparable serum calcium at 6 months (8.7 ±â€…0.4 vs 8.9 ±â€…0.4 mg/dL, P = 0.13). Their median [interquartile range (IQR)] dose at 6 months was 2.0 (1.0-2.5) and 0.75 (0.5-1.0) µg/d, respectively. Serum 1,25(OH)2D levels were physiological in both (35.3 ±â€…11.6 and 32.3 ±â€…16.9 pg/mL). Serum phosphate and calcium excretion were comparable in 2 arms. A majority had hyperphosphatemia (75% vs 76%), hypercalciuria (75% vs 72%), and elevated FGF23 (116 ±â€…68 and 113 ±â€…57 pg/mL). Age showed significant independent association with plasma FGF23 (ß = 1.9, P = 0.001). Average FEPh was low despite high FGF23. CONCLUSION: At optimal calcium control, both alfacalcidol and calcitriol lead to comparable but high serum phosphate levels, hypercalciuria, physiological circulating 1,25(OH)2D, and elevated FGF23. Further studies are required to systematically investigate other treatment options.

Osteogenic Mechanisms of Basal Ganglia Calcification and its ex vivo Model in the Hypoparathyroid Milieu.

CONTEXT: Basal-ganglia calcification (BGC) is common (70%) in patients with chronic hypoparathyroidism. Interestingly, cortical gray matter is spared from calcification. The mechanism of BGC, role of hyperphosphatemia, and modulation of osteogenic molecules by parathyroid hormone (PTH) in its pathogenesis is not clear. OBJECTIVE: We assessed the expression of a large repertoire of molecules with proosteogenic or antiosteogenic effects, including neuroprogenitor cells in caudate, dentate, and cortical gray matter from normal autopsy tissues. The effect of high phosphate and PTH was assessed in an ex vivo model of BGC using striatum tissue culture of the Sprague-Dawley rat. METHODS: The messenger RNA and protein expression of 39 molecules involved in multiple osteogenic pathways were assessed in 25 autopsy tissues using reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. The striatal culture was maintained in a hypoparathyroid milieu for 24 days with and without (a) high phosphate (10-mm ß-glycerophosphate) and (b) PTH(1-34) (50 ng/mL Dulbecco's modified Eagle's medium-F12 media) for their effect on striatal calcification and osteogenic molecules. RESULTS: Procalcification molecules (osteonectin, ß-catenin, klotho, FZD4, NT5E, LRP5, WNT3A, collagen-1α, and SOX2-positive neuroprogenitor stem cells) had significantly higher expression in the caudate than gray matter. Caudate nuclei also had higher expression of antiosteogenic molecules (osteopontin, carbonic anhydrase-II [CA-II], MGP, sclerostin, ISG15, ENPP1, and USP18). In an ex vivo model, striatum culture showed an increased propensity for calcified nodules with mineral deposition similar to that of bone tissue on Fourier-transformed infrared spectroscopy, alizarin, and von Kossa stain. Mineralization in striatal culture was enhanced by high phosphate and decreased by exogenous PTH through increased expression of CA-II. CONCLUSION: This study provides a conceptual advance on the molecular mechanisms of BGC and the possibility of PTH therapy to prevent this complication in a hypoparathyroid milieu.

Prevalence of species-specific candidiasis and status of oral hygiene and dentition among diabetic patients: A hospital-based study.

OBJECTIVE: The study was undertaken to estimate the species-specific prevalence of oral candidiasis in diabetic individuals in India, and further find the relationship of oral carriage of Candida in diabetes with degree of diabetic control, duration of disease, type of diabetes and its effect on the status of oral hygiene status and decayed, missing and filled teeth (DMFT) score. METHODOLOGY: The prospective cross-sectional study involved 900 individuals (470 diabetic and 430 non-diabetic) visiting a tertiary care hospital. Informed consent was obtained from all the individuals participating in the study. The demographic details, medical history and oral cavity examination were recorded in a specially designed proforma. Swabs were taken for microbiological evaluation for specific prevalence of Candida. RESULTS: The overall prevalence of Candida in diabetics was 22.1% as compared to 9.7% in non-diabetic individuals. However, among the type 1 and type 2 diabetics, the prevalence of Candida was equally distributed as 22.6% and 20.8%, respectively. C. albicans was the most common species (97.1%), while isolated cases of other species like C. rugosa, C. tropicalis, C. glabrata were also observed. The individuals with higher glycaemic score (HbA1c >7) showed higher prevalence of oral candidiasis. Oral hygiene status was observed to be lower among diabetics as compared to non-diabetic individuals. CONCLUSION: Oral candidiasis was more prevalent in diabetic patients, and C. albicans was the most common species. The diabetics also showed higher mean DMFT with lower oral hygiene status as compared to non-diabetic individuals.

Hyperplastic thyroid nodule masquerading as parathyroid adenoma in a patient with tubercular lymphadenitis induced hypercalcaemia.

Serum intact parathyroid hormone (iPTH) levels are high or high normal in patients with parathyroid adenoma. Rarely these patients can have normal or low serum iPTH values. With sandwich immunometric assays, an exceptionally high serum iPTH level can lead to falsely low measurement due to the 'hook effect'. Here, we describe the case of a 66-year-old female patient with PTH-independent hypercalcaemia which mimicked parathyroid adenoma. A multidisciplinary team approach helped in the diagnosis and management leading to complete recovery.

Nephrocalcinosis, Renal Dysfunction, and Calculi in Patients With Primary Hypoparathyroidism on Long-Term Conventional Therapy.

CONTEXT: There are concerns about the long-term safety of conventional therapy on renal health in patients with hypoparathyroidism. Careful audit of these would help comparisons with upcoming parathyroid hormone therapy. OBJECTIVE: We investigated nephrocalcinosis, renal dysfunction, and calculi, their predictors and progression over long-term follow-up in patients with primary hypoparathyroidism (PH). DESIGN AND SETTING: An observational study at a tertiary care center was conducted. PARTICIPANTS AND METHODS: A total of 165 PH patients receiving conventional therapy were evaluated by radiographs, ultrasonography, and computed tomography. Their glomerular filtration rate (GFR) was measured by Tc-99m-diethylenetriamine penta-acetic acid clearance. Clinical characteristics, serum total calcium, phosphorus, creatinine, hypercalciuria, and fractional excretion of phosphorus (FEPh) at presentation and during follow-up were analyzed as possible predictors of renal complications. Controls were 165 apparently healthy individuals. RESULTS: Nephrocalcinosis was present in 6.7% of PH patients but not in controls. Patients younger than 15 years at presentation and with higher serum calcium-phosphorus product were at higher risk. Nephrocalcinosis showed no significant association with cataract and intracranial calcification. Prevalence of renal calculi was comparable between hypoparathyroid patients and controls (5% vs 3.6%, P = .58). Fourteen percent of patients had a GFR less than 60 mL/min/1.73 m2. Increased FEPh during follow-up was the significant predictor of low GFR. Nephrocalcinosis developed in 9% of patients over 10 years of conventional therapy. CONCLUSION: A total of 6.7% of PH patients had nephrocalcinosis, and 14% showed renal dysfunction. Prevalence of renal calculi was similar in patients and controls. Nine percent of patients developed nephrocalcinosis over 10 years of conventional therapy.

Antioxidants for Pancreatic Functions in Chronic Pancreatitis: A Double-blind Randomized Placebo-controlled Pilot Study.

BACKGROUND: Antioxidants (AO) supplementation in chronic pancreatitis (CP) has been evaluated for pain. But it is not clear whether AO in CP have an effect on pancreatic functions and other clinical outcomes. We evaluated effect of AO on endocrine function in CP. MATERIALS AND METHODS: Double-blind placebo (PL)-controlled randomized pilot study on 107 patients with CP assigned to receive daily combined AO or PL for 6 months. Primary outcome was: improvement in endocrine function (Homeostasis Model Assessment-Insulin Resistance). Secondary outcome measures were: improvement in C-peptide, Qualitative Insulin Sensitivity Check Index, exocrine pancreatic function (fecal elastase), surrogate markers of fibrosis (platelet-derived growth factor BB, transforming growth factor-ß1, α-smooth muscle actin), quality of life (QOL), pain, nutritional status, markers of oxidative stress (OS), AO status, and inflammation. RESULTS: There was an increase in levels of serum selenium (107.2±26.9 to 109.7±26.9 vs. 104.1±28.6 to 124.0±33.6 µg/L, P=0.022) and serum vitamin E [0.58 (range, 0.27-3.22) to 0.66 (range, 0.34-1.98) vs. 0.63 (range, 0.28-1.73) to 1.09 (range, 0.25-2.91) mg/dL, P=0.001] in the AO than the PL group. However, no significant differences were observed between groups in any of the primary or secondary outcome measures. CONCLUSIONS: Supplementation with AO to patients with CP causes a sustained increase in blood levels of AO; however, it has no addition benefit over PL on endocrine and exocrine functions, markers of fibrosis, OS and inflammation, nutritional status, pain and QOL. Further larger studies with adequate sample size are required.

Pulmonary alveolar proteinosis (PAP) in idiopathic hypoparathyroidism.

Idiopathic hypoparathyroidism (IH) and autoimmune pulmonary alveolar proteinosis (PAP) are rare disorders. A patient with IH and optimal calcaemic control on calcium and alfacalcidol was detected to have PAP after 8 years of follow-up. Patient had no respiratory complaints. Routine abdominal imaging for renal calcification showed patchy ground glass opacities in the lower lung fields leading to incidental diagnosis of PAP. Pulmonary function tests showed impaired diffusion capacity of the lung. Anti-granulocyte macrophage-colony stimulating factor autoantibodies were positive. Patient regularly attended the pulmonary clinic and showed progressive improvement in diffusion capacity of the lung during 2 years of follow-up. The calcaemic control in IH remained stable despite its presence with PAP. The autoimmune PAP in the presented case suggests a possible autoimmune basis of IH.

Central Immune Tolerance of T and B Cells in Patients With Idiopathic Hypoparathyroidism, T1D, and Autoimmune Thyroiditis.

CONTEXT: Pathogenesis of idiopathic hypoparathyroidism (IH) is under investigation. Abnormalities in central immune tolerance have yet not been investigated in this condition. T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs), formed during receptor gene rearrangements, are tools to assess central T- and B-cell output. OBJECTIVE: We assessed the number of circulating TRECs and KRECs in patients with IH, autoimmune type 1 diabetes (T1D), and autoimmune thyroiditis (ATs) and healthy controls (HCs). DESIGN: Comparative case-control at tertiary care center. SUBJECTS AND METHODS: Absolute and relative TRECs and KRECs were measured in DNA extracted from whole blood of patients with IH (n = 181, 22 of whom were reassessed after a decade of follow-up) and T1D (n = 133), AT (n = 53), and HC (n = 135) using a quantitative real-time PCR/TaqMan® probe technique. RESULTS: Absolute and relative means of TRECs and KRECs in IH were comparable to HCs, and no differences were found between IH with and without calcium-sensing receptor antibodies or class I HLA-A*26:01 association. TRECs and KRECs did not change after a decade of follow-up. T1D had significantly higher absolute TRECs than IH, AT, and HCs, whereas AT patients showed lower TRECs and the highest KRECs; these levels showed no noteworthy correlation with thyroid dysfunctions. CONCLUSION: Patients with IH showed TRECs and KRECs comparable to HCs, indicating an intact mechanism of T- and B-cell central immune tolerance. Interestingly, absolute TRECs were significantly higher in T1D than HCs, suggesting impaired central immune tolerance in T1D.

Absence of vitamin D deficiency among common outdoor workers in Delhi.

BACKGROUND: There is reservation about accepting the notion of widespread vitamin D deficiency (VDD) in sunny countries because information base is largely urban indoors, and the cut-off serum 25(OH)D > 75.0 nmol/L to define sufficiency is perceived as high. OBJECTIVE: We assessed the vitamin D status of subjects engaged in six types of outdoor jobs with freedom to seek shade, when needed. DESIGN: Descriptive observational study. SUBJECTS AND METHODS: A total of 573 outdoors, (hawkers, n = 144; auto-rickshaw drivers, n = 113; manual rickshaw pullers, n = 49; fuel-station attendants, n = 84; gardeners, n = 96; traffic police personnel, n = 87) were assessed for serum 25(OH)D, iPTH and total calcium during summer and winter. Bank employees were indoor controls (n = 72). Serum 25(OH)D was defined as sufficient if ≥50.0 nmol/L and deficient when <30.0 nmol/L, as per 'Institute of Medicine'. RESULTS: Mean serum 25(OH)D of 573 outdoors was 44.8 ± 19.6 nmol/L and showed a physiological inverse relation with iPTH (P < 0.001). 77.5% of the outdoors did not have VDD. Hawkers, gardeners, fuel-station attendants and rickshaw pullers had sufficient or near sufficient serum 25(OH)D. The mean serum 25(OH)D (30.6 ± 23.2 nmol/L) of indoors though lower by 12.7 nmol/L than outdoors was above the cut-off of VDD. Proportions with supranormal iPTH were comparable between outdoors and indoors (14.0% vs 20.8%). Despite winter dip, the mean serum 25(OH)D (31.2 ± 14.3 nmol/l) of outdoors was not deficient. CONCLUSIONS: Vitamin D deficiency is not universal. Most urban outdoor workers do not have VDD.