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Aims: Patient satisfaction is associated with positive diabetes outcomes. However, there are no identified studies that evaluate both patient‐ and clinic‐level predictors influencing diabetes care satisfaction longitudinally. Methods: Data from the INtegrating DEPrEssioN and Diabetes treatmENT trial was used to perform the analysis. We used fixed and random effects models to assess whether and how changes in patient‐level predictors (treatment assignment, depression symptom severity, systolic blood pressure, body mass index, LDL cholesterol, and haemoglobin A1C) from 0 to 24 months and clinic‐level predictors (visit frequency, visit cost, number of specialists, wait time, time spent with healthcare provider, and receiving verbal reminders) measured at 24 months influence diabetes care satisfaction from 0 to 24 months. Results: Model 1 (patient‐level predictors) accounted for 7% of the change in diabetes satisfaction and there was a significant negative relationship between change in depressive symptoms and care satisfaction (β = −0.23, SE = 0.12, p < 0.05). Within Model 1, 2% of the variance was explained by clinic‐level predictors. Model 2 included both patient‐ and clinic‐level predictors and accounted for 18% of the change in diabetes care satisfaction. Within Model 2, 9% of the variance was attributed to clinic‐level predictors. There was also a cross‐level interaction where the change in depression had less of an impact on the change in satisfaction for those who received a verbal reminder (β = −0.11, SE = 0.21, p = 0.34) compared with those who did not receive a reminder (β = −0.62, SE = 0.08, p < 0.01). Conclusions: Increased burden of depressive symptoms influences diabetes care satisfaction. Clinic‐level predictors also significantly influence diabetes care satisfaction and can reduce dissatisfaction in primary care, specifically, reminder calls from clinic staff. [ABSTRACT FROM AUTHOR]

Aims: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non‐physician care coordinators to promote adherence and clinical decision‐support software to enhance physician practices, in comparision with usual care. Methods: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c<53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non‐smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11‐mmol/mol (1%) reduction in HbA1c, ≥10‐mmHg reduction in systolic blood pressure, and/or ≥0.26‐mmol/l reduction in LDL cholesterol. Results: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c, blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. Conclusions: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher‐risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality‐of‐care goals is challenging and that other methods may be needed in closing care gaps. What's new?: Quality improvement interventions targeting multiple risk factors in diabetes can lower the risk of disabling complications.In this post hoc analysis of the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) randomized controlled trial, the multicomponent quality improvement intervention (comprising non‐physician care coordinators and clinical decision‐support electronic health records) was associated with higher achievement of composite diabetes quality targets and clinically significant improvements in cardiometabolic indices; however, only small proportions of these participants with poor glycaemic control achieved the complete group of five targets.Multicomponent quality improvement can improve achievement of diabetes quality targets, and perhaps more importantly, can lead to improvements in care indices that may mitigate complications for people with diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D deficiency (VDD) is globally well documented among school children. Objective: To study the effect of vitamin D, fortified milk on vitamin D status of apparently healthy school children (aged 10-14 years). Materials and Methods: This prospective interventional study was carried out in 713 subjects, randomized into 3 groups, group A (n =237) unfortified milk, Group B (n =243) 600 IU of vitamin D and group C (n =233) 1000 IU vitamin D for 12 weeks. Serum 25 hydroxy vitamin D (SVitD) level was measured by electrchemiluminometric assay along with serum calcium and urinary calcium creatinine ratio at baseline and 12 weeks post supplementation. Results: VDD (SVitD <20 ng/ml) reported in 92.3% subjects (boys 88%; girls 95.4%; p <0.001), with mean SVitD level 11.6 ± 5.3 ng/ml. There was no significant difference in SVitD among three groups at baseline. SVitD levels significantly improved in all 3 groups. In control group, only 5.9% had vitamin D level more than 20 ng/mL after fortification while group B and C had 69.95% and 81.11% subjects had SVitD >20 ng/mL. Similarly, vitamin D sufficiency (>30 ng/mL) was seen in 1.26% subjects in group A; 12.34% in group B and 36.05% subjects in group C after fortification. The mean improvement in serum vitamin D level in group A was 5.25% while group B had mean improvement of 137.97% and group C had mean improvement of 177.29%. Conclusion: Fortification of milk with vitamin D is effective and safe in preventing VDD in apparently healthy school children. [ABSTRACT FROM AUTHOR]

Aims: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in people with diabetes in South Asia. The CARRS Translation Trial tests the effectiveness, cost-effectiveness, and sustainability of a clinic-based multi-component CVD risk reduction intervention among people with diabetes in India and Pakistan.Methods: We randomly assigned 1146 adults with diabetes recruited from 10 urban clinic sites, to receive usual care by physicians or to receive an integrated multi-component CVD risk reduction intervention. The intervention involves electronic health record management, decision-support prompts to the healthcare team, and the support of a care coordinator to actively facilitate patient and provider adherence to evidence-based guidelines. The primary outcome is a composite of multiple CVD risk factor control (blood glucose and either blood pressure or cholesterol, or all three). Other outcomes include control of the individual CVD risk factors, process and patient-centered measures, cost-effectiveness, and acceptability/feasibility.Conclusion: The CARRS Translation Trial tests a low-cost diabetes care delivery model in urban South Asia to achieve comprehensive cardio-metabolic disease case-management of high-risk patients (clinicaltrials.gov number: NCT01212328). [ABSTRACT FROM AUTHOR]

Background. Phosphaturic mesenchymal tumor (PMT) is a recently described concept unifying the mesenchymal tumor associated with oncogenic osteomalacia. Most of the cases of PMT occur in the extremities and appendicular skeleton. PMT occurring in the paranasal sinuses is extremely rare with only a few cases reported in the available literature. Case. A 51-year-old man presented with a long history of bone pains. Biochemical and radiologic investigations, including skeletal survey showed features of osteomalacia. Positron emission tomography (PET) scan showed a small tumor in the left nasal cavity, ethmoid and sphenoid sinuses. Histopathological examination of the excised tumor showed features of a phosphaturic mesenchymal tumor- mixed connective tissue variant. Excision of the tumor was associated with marked improvement in the biochemical parameters and remarkable clinical relief. Conclusion. Phosphaturic mesenchymal tumor is a rare cause of osteomalacia and is usually associated with small tumors, which escape detection for long periods. Its occurrence in the paranasal sinuses needs to be kept in mind and evaluated to allow for timely detection of the tumor with subsequent surgical excision and clinico-biochemical relief. [ABSTRACT FROM AUTHOR]

Background: Obesity is among the leading public health threats globally. Over the last few years, visceral adiposity index (VAI), and body adiposity index (BAI), derived from anthropometric, and biochemical measures, have gained importance as a measure of obesity. However, unlike other common indices like body mass index, and waist circumference, the genetic predisposition of VAI, and BAI under-examined., Methods: 2265 sib-pairs from Indian Migration Study were used for examining the association of genetic variants from the Cardio-Metabochip array with VAI, and BAI. Mixed linear regression models were run, and all inferences were based on the within-sib component of the Fulker's association models. Gene-environment/lifestyle interaction analyses were also undertaken., Results: rs6659428 at LOC400796 | SEC16B (β = 0.26, SE = 0.05), and rs7611535 at DRD3 | LOC645180 (β = 0.18, SE = 0.04) were associated with VAI at suggestive significance value of <8.21 × 10 -6 . For BAI, rs73300702 at JAZF1-AS1 (β = 0.27, SE = 0.06), was the top hit at p value < 8.21 × 10 -6 . Further, rs6659428 showed marginal effect modification with rural/urban location (β = 0.26, SE = 0.13, p value = 0.047), and rs73300702 with physical activity (β = -0.29,SE = 0.14, p value = 0.034)., Conclusion: We report three novel genetic loci for VAI, and BAI in Indians that are important indicators of adiposity. These findings need to be replicated and validated with larger samples from different ethnicities. Further, functional studies for understanding the biological mechanisms of these adiposity indices need to be undertaken to understand the underlying pathophysiology., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: We determined whether endoscopic thyroidectomy (ET) is associated with better health-related quality of life (QoL) compared with open thyroidectomy., Methods: We randomly assigned 28 patients aged older than 18 years, Bethesda IV or less on cytology and gland volume of <40 mL to undergo hemithyroidectomy through either open or endoscopic (axillo-breast approach/bilateral axillo-breast approach) technique. The primary outcome was QoL scores on the Short Form-36 and Thyroid-Specific Questionnaire at 2, 6, and 12 weeks postsurgery. Secondary outcomes were postoperative complications, hospital stay, and pain scores., Results: The generic QoL scores based on Short Form-36 were statistically nonsignificant between the two groups. QoL scores based on Thyroid-Specific Questionnaire were statistically significant ( P < 0.05) favoring open thyroidectomy in the following domains: (1) numbness at 2, 6, and 12 weeks ( P = 0.04, 0.004, and 0.005, respectively), (2) shoulder impairment at 2 weeks ( P = 0.017), and (3) favoring ET in cosmesis at 6 and 12 weeks ( P = 0.037 and 0.02, respectively). ET has longer operative time (104.6 ± 25.4 vs 123 ± 8.9 min; P = 0.03), longer hospital stays (2.8 ± 0.4 vs 2.4 ± 0.5; P = 0.056) and higher pain scores at 2 and 6 weeks ( P = 0.007 and 0.012, respectively) but decreased intraoperative bleeding (33.5 ± 6.4 vs 29.1 ± 3.7 mL; P = 0.037)., Conclusion: ET has higher cosmetic satisfaction, increased numbness, and shoulder movement impairment during short-term postsurgery follow-up. Both techniques are similar in impacting general physical, mental, and social health-related QoL. (Clinical Trials Registry of India, Reg. No. CTRI/2020/07/026374)., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Endonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas are considered the gold standard treatment for Cushing disease (CD). Even with various recent advances in management, disease persistence and recurrence are common in these patients. The remission rate in the global population after surgery has been reported to vary widely from 64% to 93%. This study aims to determine the various clinical, biochemical, radiological, and histological factors that correlate with persistence and recurrence in patients with CD. This study also aims to understand the clinicopathological significance of EGFR-MAPK, NF-κB, and SHH pathway activation and to study the protein expression of activation markers of these pathways (i.e., c-Fos, c-Jun, GLI-1, pMEK, NR4A1, and p44) in functioning corticotroph pituitary adenomas., Methods: From January 2009 to September 2022, the clinical data of 167 patients who underwent surgical treatment (n = 174 surgeries) for CD with a median follow-up of 8.1 years (range, 1-13.29 years) were ambispectively analyzed. The preoperative clinical, biochemical, and radiological features, operative findings, postoperative clinical and biochemical data, and histopathological and molecular profiles were retrieved from the electronic medical records. The patients were followed up to assess their remission status., Results: Among the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for pediatric patients, and 12 surgeries were for patients with Nelson syndrome. In the primary surgery cohort, 74.3% were female, and the average age was 28.73 ± 10.15 years. Of the primary surgery cohort, 75% of the patients experienced remission compared with 47.4% after revision surgery. The remission rate for the pediatric patients was 55.5%. The postoperative day 1 plasma cortisol (P < 0.001; area under the curve, 0.8894; range, 0.8087-0.9701) and adrenocorticotropic hormone (P < 0.001; area under the curve, 0.9; range, 0.7386-1) levels were seen to be strong independent predictors of remission in the primary surgery cohort. The remission rate after endoscopic TSS was greater than that after microscopic TSS in patients undergoing primary surgery (81.08% vs. 57.14%; P = 0.008). The presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (P = 0.020). On stratifying by surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of nonremission (odds ratio, 38.1; 95% confidence interval, 4.2-348.3) compared with endoscopically operated patients with adenoma found on HPE. A lower immunoreactivity score for NR4A1 was found to correlate with higher remission rates (P = 0.074). However, none of the molecular markers studied (i.e., c-Fos, c-Jun, GLI-1, pMEK, and p44) showed a significant correlation with the preoperative cortisol values., Conclusions: The remission rate after primary surgery is higher than that after revision surgery and is lower for pediatric patients than for adults. The postoperative day 1 plasma cortisol and adrenocorticotropic hormone levels are strong independent predictors of remission in the primary surgery cohort. An endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate; thus, endoscopy should be the approach of choice for these patients with the goal of identification of an adenoma on HPE., (Copyright © 2024. Published by Elsevier Inc.)

Background: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial., Methods and Findings: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention., Conclusions: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes., Trial Registration: ClinicalTrials.gov NCT01212328., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MKA has received research support (to Emory University) from Merck and consulting fees from Bayer and Eli Lilly, all outside the scope of this work. SP received research funding in the area of CVD implementation sciences. All other authors have declared that no competing interests exist., (Copyright: © 2024 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals., Methods: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned., Results: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions., Conclusions: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide., Competing Interests: Declaration of competing interest Raman Puri: Boehringer Ingelheim, Novartis Manish Bansal: Sun Pharmaceuticals, USV, Dr Reddy's Labs, Cipla, Eris Lifesciences, Intas Pharmaceuticals, AstraZeneca Pharma India, Novartis Vimal Mehta: Institutional research grants from Amgen, Boehringer Ingelheim, Novo Nordisk, Eli Lilly, LIB Therapeutics, AstraZeneca, Torrent P Barton Duell: Advisory activities: Akcea/Ionis, Esperion, Regeneron, Kaneka, Novo Nordisk. Institutional grants: Regeneron, Regenxbio, Retrophin/Travere Nathan Wong: Research support through UC Irvine: Regeneron, Novo Nordisk, Novartis, Eli Lilly, Consultant: Novartis, Ionis, Agepha SS Iyengar: Reddy's Lab, Amgen, Emcure, Glenmark, Boehringer Ingelheim, Pfizer, Novartis Devaki Nair: Novartis, Daichi Sankyo Krishnaswami Vijayaraghavan: Amgen, AstraZeneca, Boehringer Ingelheim, Esperion, Novo Nordisk, Pfizer V Mohan: Servier, MSD, Novo Nordisk, Novartis, Eli Lilly, USV, Lifescan J & J, Sanofi Aventis, Merck, Boehringer Ingelheim, Abbott, Several Indian Pharmaceutical companies Shashank Joshi: Biocon, Cadilla, Twin Health, Glenmark, Torrent, Marico, MSD, Novo Nordisk, Sanofi, Boehringer Ingelheim, Abbott, AstraZeneca, USV, Alkem, Serdia Saumitra Ray: Merck, Novartis, Boehringer Ingelheim, Astra Zeneca, Novartis Sandeep Bansal: Novo Nordisk, Vascular Innovations Co. Ltd, Bayer, Portico India, ICMR SN Narasingan: IPCA, Novartis, USV, Torrent, SUN Pharma J C Mohan: Novartis, Lupin, Sun pharmaceuticals, Astra Zeneca, Intas, Le Servier, Sanofi Other authors report no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Primary hyperparathyroidism is mostly caused by parathyroid adenoma(s) which are generally localized using routine imaging modalities such as neck ultrasonography and 99m Tc-SestaMIBI scintigraphy. However, these can miss ectopic parathyroid adenomas due to their limited sensitivities. These ectopic lesions can later lead to failure of surgical excision and necessitate the need for a re-exploration. 18 F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) can help in the localization of these ectopic adenomas due to its superior detection rates and spatial resolution. Herein, we report a case of ectopic parathyroid adenomas that were localized on FCH PET/CT., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Nuclear Medicine.)

Introduction: To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature., Methods: It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency., Results: A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%)., Conclusion: Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR)., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Endocrinology and Metabolism.)

Platelet activation and related cardiovascular complications are the hallmarks of type 2 diabetes (T2D). We investigated the mechanism of platelet activation in T2D using MS-based identification of differentially expressed platelet proteins with a focus on glycosylated forms. Glycosylation is considered one of the common post-translational modifications in T2D, and N/O-linked glycosylation of glycoproteins (GPs)/integrins is known to play crucial roles in platelet activation. Our platelet proteome data revealed elevated levels of GPs GPIbα, GPIIbIIIa, GPIV (CD36), GPV and integrins in T2D patients. T2D platelets had elevated N-linked glycosylation of CD36 at asparagine (Asn) 408,417 . Enrichment analysis revealed a close association of glycosylated CD36 with thrombospondin-1, fibrinogen and SERPINA1 in T2D platelets. The glycosylation of CD36 has previously been reported to increase cellular uptake of long-chain fatty acids. Our in silico molecular docking data also showed a favorable binding of cholesterol with glycosylated Asn 417 CD36 compared to the non-glycosylated form. We further investigated the CD36:LDL cholesterol axis in T2D. Elevated levels of oxidized-low density lipoprotein (oxLDL) were found to cause significant platelet activation via CD36-mediated stimulation of Lyn-JNK signaling. Sulfo-N-succinimidyl oleate, an inhibitor of CD36, effectively inhibited oxLDL-mediated platelet activation and adhesion in vitro. Our study suggests increased glycosylation of CD36 in T2D platelets as a potential route for oxLDL-mediated platelet activation. The oxLDL:CD36 axis may thus be exploited as a prospective target to develop therapeutics against thrombosis in T2D., (© 2023 Federation of European Biochemical Societies.)

The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis, and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate metabolite as an inhibitor to platelets and leukocytes activation by suppressing phosphorylated-Akt (pAkt) through augmentation of prolyl hydroxylase-2 (PHD2). Dietary supplementation with a pharmacological concentration of αKG significantly inhibited lung inflammation in mice with either SARS-CoV-2 infection or exposed to hypoxia treatment. We therefore investigated if αKG supplementation could suppress hyperactivation of these blood cells and reduce thromboinflammatory complications in T2D. Our study describes that dietary supplementation with αKG (8 mg/100 g body wt. daily) for 7 days significantly reduced the activation of platelets and leukocytes (neutrophils and monocytes), and accumulation of IL1β, TNFα, and IL6 in peripheral blood of T2D mice. αKG also reduced the infiltration of platelets and leukocytes, and accumulation of inflammatory cytokines in lungs by suppressing pAkt and pP65 signaling. In a cross-sectional investigation, our study also described the elevated platelet-leukocyte aggregates and pro-inflammatory cytokines in circulation of T2D patients. T2D platelets and leukocytes showed an increased aggregation and thrombus formation in vitro. Interestingly, a pre-incubation of T2D blood samples with octyl αKG significantly suppressed the activation of these blood cells and ameliorated aggregate/thrombus formation in vitro. Thus, suggesting a potential therapeutic role of αKG against inflammation, thrombosis, and CVDs in T2D., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Changes in skeletal muscle mass and quality are associated with type 2 Diabetes (T2D) and its complications. We evaluated the prevalence of sarcopenia in patients with T2D and its association with various anthropometric and metabolic parameters., Methods: A total of 229 patients with T2D, ≥20-60 years, were screened for sarcopenia using handgrip strength (HGS) by dynamometer, physical performance test (by Short Physical and chair stand test), and height-adjusted appendicular skeletal muscle index (ASMI) by Dual Energy X-ray Absorptiometry (DXA) applying Asian Working Group on Sarcopenia (AWGS). Multiple logistic regressions were performed to identify the factors associated with sarcopenia., Results: The mean age was 46.2 ± 7.4 years with 55% being women. The prevalence of low HGS, poor physical performance, low ASMI, possible sarcopenia, sarcopenia, and severe sarcopenia was 16.2%, 39.3%, 33%, 43%, 18.8%, and 6.1%, respectively. Age >45 years and use of >2 oral hypoglycaemic agents (OHA's) were risk factors for low HGS (OR:3.51, 95%CI = 1.5-8.3) and low ASMI (OR:2.40, 95%CI = 1.05, 5.49, p-0.04), respectively. Female sex (OR:3.3 1.8-6.1 p < 0.01), age >45 years (OR:2.12, 95% CI = 1.2-3.8 p-0.012) and liver fibrosis (OR: 2.12, 95% CI = 1.01-4.46 p-0.048) were independently associated with poor performance. No association was found with HbA1c, dyslipidaemia, albuminuria, hypertension, or duration of diabetes and sarcopenia., Conclusion: Sarcopenia is becoming increasingly recognized as a significant complication in younger individuals with T2D, and poor physical performance plays a vital role in its development. The prevalence of sarcopenia rises with advancing age, underscoring the importance of early intervention to address this condition., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Adiposity has gradually become a global public threat over the years with drastic increase in the attributable deaths and disability adjusted life years (DALYs). Given an increased metabolic risk among Asians as compared to Europeans for any given body mass index (BMI) and considering the differences in genetic architecture between them, the present review aims to summarize the findings from genome-wide scans for various adiposity indices and related anthropometric measures from Asian populations. The search for related studies, published till February 2022, were made on PubMed and GWAS Catalog using search strategy built with relevant keywords joined by Boolean operators. It was recorded that out of a total of 47 identified studies, maximum studies are from Korean population (n = 14), followed by Chinese (n = 7), and Japanese (n = 6). Nearly 200 loci have been identified for BMI, 660 for height, 16 for weight, 28 for circumferences (waist and hip), 32 for ratios (waist hip ratio [WHR] and thoracic hip ratio [THR]), 5 for body fat, 16 for obesity, and 28 for adiposity-related blood markers among Asians. It was observed that though, most of the loci were unique for each trait, there were 3 loci in common to BMI and WHR. Apart from validation of variants identified in European setting, there were many novel loci discovered in Asian populations. Notably, 125 novel loci form Asian studies have been reported for BMI, 47 for height, 5 for waist circumference, and 2 for adiponectin level to the existing knowledge of the genetic framework of adiposity and related measures. It is necessary to examine more advanced adiposity measures, specifically of relevance to abdominal adiposity, a major risk factor for cardiometabolic disorders among Asians. Moreover, in spite of being one continent, there is diversity among different ethnicities across Asia in terms of lifestyle, climate, geography, genetic structure and consequently the phenotypic manifestations. Hence, it is also important to consider ethnic specific studies for identifying and validating reliable genetic variants of adiposity measures among Asians., (© 2023 John Wiley & Sons Ltd/University College London.)

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family. It plays a significant role in the regulation of brain metabolic activity, modification of synaptic efficacy, and enhances neuronal survival. A common naturally occurring allelic variation, i.e. G196A (Val66 Met, rs6265) of the BDNF gene is implicated in neuroplasticity. This study analyzes its expression levels and determines the frequency of BDNF G196A gene polymorphism in women with Turner syndrome (TS) compared to the controls. This case-control study comprised 14 TS patients and 8 healthy individuals. The expression levels of BDNF gene in TS patients were checked by qPCR. For BDNF gene, a dynamic expression range along with the presence of G196A polymorphism was found across all TS patients. The effects of Val66 Met mutation on BDNF protein structure and function were studied by molecular dynamics simulations of wild and mutant (Val66 Met) forms. The analysis of different trajectories generated by simulation showed that there was a significant change in the protein structure due to Val66 Met polymorphism, which might lead to functional impairment. This is first time we are reporting the association of BDNF G196A gene polymorphism with TS risk. Our study suggests that in turner patients, BDNF G196A polymorphism may be an important genetic factor predisposing to neuroplasticity risk and can be exploited as diagnostic/prognostic marker for TS. Further study on a large number of TS samples will prove this point beyond doubts or otherwise enriching the much desired repertoire of personalized medicine.

Purpose: Hereditary tumor syndrome Von Hippel-Lindau (VHL) disease is characterized by various benign and malignant tumors that are known to express somatostatin receptors (SSTR). We evaluated the role of 68 Ga-DOTANOC PET/CT scan in patients with positive germline mutation of the VHL gene, presented initially or on follow-up, for the detection of recurrent or synchronous/metachronous lesions., Methods: Fourteen patients (8 males; 6 females) with mean age 30 ± 9.86 years were retrospectively analyzed, were tested positive for VHL on gene dosage analysis, and underwent 68  Ga-DOTANOC PET/CT scan for disease evaluation. The number and site of lesions were determined. The tracer uptake was analyzed semi-quantitatively by calculating the maximum standardized uptake values (SUVmax) of lesion., Results: Four of the 14 patients underwent scan for initial diagnosis as baseline, 6 patients for post-therapy disease status, and 4 patients for initial diagnosis as well as follow-up evaluation of the disease. A total of 67 lesions were detected in 14 patients. The sites of lesions were cerebellar/vertebral/spinal (17; mean SUVmax = 7.85); pancreatic neuroendocrine tumor (NET) (11; mean SUVmax = 20.64); retina (3; mean SUVmax = 10.46); pheochromocytoma (10; mean SUVmax = 16.32); paragangliomas (3; mean SUVmax = 10.65); pancreatic cyst (9; mean SUVmax = 2.54); and renal cyst (8; mean SUVmax = 1.56) and miscellaneous lesions constituted 6 lesions., Conclusion: Our results show that 68  Ga-DOTANOC PET/CT may be a useful modality for screening and follow-up of associated tumors in patients with germline gene mutation for VHL. It can be used as a one-stop imaging modality for VHL patients and may substitute for separate radiological investigations, making it more convenient for patients in terms of time and cost., Competing Interests: Conflict of InterestShamim Ahmed Shamim, Geetanjali Arora, Naresh Kumar, Jhangir Hussain, Shreya Datta Gupta, Arun Raj ST, Kritin Shankar, Alpesh Goyal, Rajesh Khadgawat, Sambit Sagar, and Chandrasekhar Bal declare no conflict of interest., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: More than 250 loci have been identified by genome-wide scans for type 2 diabetes in different populations. South Asians have a very different manifestation of the diseases and hence role of these loci need to be investigated among Indians with huge burden of cardio-metabolic disorders. Thus the present study aims to validate the recently identified GWAS loci in an endogamous caste population in North India., Methods: 219 T2D cases and 184 controls were recruited from hospitals and genotyped for 15 GWAS loci of T2D. Regression models adjusted for covariates were run to examine the association for T2D and fasting glucose levels., Results: We validated three variants for T2D namely, rs11634397 at ZFAND6 (OR = 3.05, 95%CI = 1.02-9.19, p = 0.047) and rs8042680 at PRC1 (OR = 3.67, 95%CI = 1.13-11.93, p = 0.031) showing higher risk and rs6813195 at TMEM154 (OR = 0.28, 95%CI = 0.09-0.90, p = 0.033) showing protective effect. The combined risk of 9 directionally consistent variants was also found to be significantly associated with T2D (OR = 1.91, 95%CI = 1.18-3.08, p = 0.008). One variant rs10842994 at KLHDC5 was validated for 9.15mg/dl decreased fasting glucose levels (SE = -17.25-1.05, p = 0.027)., Conclusion: We confirm the role of ZFAND6, PRC1 and TMEM154 in the pathophysiology of type 2 diabetes among Indians. More efforts are needed with larger sample sizes to validate the diabetes GWAS loci in South Asian populations for wider applicability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Walia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia., Design: Economic evaluation from healthcare system and societal perspectives., Setting: Ten diverse urban clinics in India and Pakistan., Participants: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline., Intervention: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care., Outcome Measures: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6)., Results: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective., Conclusions: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Introduction: Successful surgical treatment for primary hyperparathyroidism requires accurate localization of abnormal parathyroid tissue in terms of location and number. Imaging is important for localizing the parathyroid adenoma, and there has been significant interest in 18 F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) for this purpose., Aim: This study attempted to ascertain the utility of 18 F-FCH PET/CT as a first-line investigation in preoperative localization of abnormal parathyroid tissue in primary hyperparathyroidism, in comparison with 99m Tc-sestamibi dual-phase scintigraphy with early single-photon emission computed tomography (SPECT)/CT and neck ultrasonography., Materials and Methods: Fifty-five patients with biochemical features of primary hyperparathyroidism were enrolled in this study. They underwent neck ultrasonography, 99m Tc-sestamibi dual-phase scintigraphy with early SPECT/CT, and 18 F-FCH PET/CT for localization of parathyroid lesions. Thirty-three patients underwent surgical resection of the detected lesions. For two patients, clinical and biochemical follow-up was used as a gold standard., Results: A total of 40 lesions were resected in the 33 patients who underwent surgery. A further two lesions were localized in two patients with clinical and biochemical follow-up as the gold standard. Of these 42 lesions, 41 were detected in preoperative imaging and 1 lesion was noted intraoperatively and resected. 41/42 lesions were detected by 18 F-FCH PET/CT (detection rate: 97.6%), 33/42 by 99m Tc-sestamibi dual-phase scintigraphy with early SPECT/CT (detection rate: 78.5%), and 30/42 by neck ultrasonography (detection rate: 71.4%)., Conclusion: Detection rates on 18 F-FCH PET/CT were superior to both 99m Tc-sestamibi dual-phase scintigraphy with early SPECT/CT and neck ultrasonography in preoperative localization of parathyroid lesions in patients with primary hyperparathyroidism., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nuclear Medicine.)

Up to 40% of Cushing's disease (CD) patients show no evidence of an adenoma on dynamic contrast-enhanced MRI. Inferior petrosal sinus sampling (IPSS) remains the gold standard for diagnosis in these patients. Remission rates in MRI-Negative CD are far less at 50%-71%, compared with patients in whom an adenoma is identified on MRI. Endoscopic endonasal transsphenoidal surgery is the surgical approach of choice in these cases. Various adjuncts can be used to localize an adenoma. In this video, the authors highlight their additional usage of pituitary perfusion MRI for identification of the adenoma. They present their stepwise management algorithm and surgical techniques for sellar and suprasellar exploration in 6 cases of MRI-Negative CD operated on by the senior author (A.S.). The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2318., Competing Interests: Disclosures Dr. Sadhwani reported a grant (no. BT/PR13455/CoE/34/24/2015) from the Department of Biotechnology, Ministry of Science and Technology, Government of India. Professor Suri reported being a principal investigator during the conduct of the study.Dr. Sadhwani reported a grant (no. BT/PR13455/CoE/34/24/2015) from the Department of Biotechnology, Ministry of Science and Technology, Government of India. Professor Suri reported being a principal investigator during the conduct of the study., (© 2023, The Authors.)

Introduction: Recurrent/persistent primary hyperparathyroidism in patients who have undergone previous parathyroidectomy is a challenging condition. Imaging is important for localizing the parathyroid adenoma for re-exploration and 18 F-Fluorocholine ( 18 F-FCH) positron emission tomography/computed tomography (PET/CT) seems ideal for this purpose., Aim: This prospective study attempted to ascertain the utility of 18 F-FCH PET/CT as an investigation in preoperative localization of abnormal parathyroid tissue in recurrent/persistent primary hyperparathyroidism while comparing it with 99m Tc-Sestamibi dual-phase scintigraphy with early single-photon emission CT (SPECT)/CT and neck ultrasonography (USG)., Methods: Twenty patients with biochemical features of recurrent/persistent primary hyperparathyroidism were enrolled into this study. They underwent neck USG, 99m Tc-Sestamibi dual-phase scintigraphy with early SPECT/CT and 18 F-FCH PET/CT for localization of parathyroid lesions. Six patients underwent surgical resection of the detected lesions, 3 were awaiting surgery, and 11 were managed conservatively. One patient died due to COVID., Results: The calculated positive predictive values on a per-lesion basis of neck USG, 99m Tc-sestamibi scintigraphy and early SPECT/CT and 18 F-FCH PET/CT in the cohort of the 5 operated patients were 75% (3/4), 71.4% (5/7), and 71.4% (5/7), respectively. On a per-patient basis, the lesion detection rate was 100% for 99m Tc-sestamibi scan and FCH PET (5/5) and 80% on neck USG (4/5)., Conclusion: 18 F-FCH PET/CT is a highly accurate imaging modality for the detection of parathyroid lesions in patients with recurrent/persistent primary hyperparathyroidism., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nuclear Medicine.)