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IntroductionPrimary hyperparathyroidism (PHPT), a third common endocrine disorder, varies from asymptomatic disease, mostly seen in the West where routine biochemical screening is practiced, to the classical symptomatic disease mostly seen in the Eastern countries. We aimed to compare the demographic, clinical, biochemical measurements in patients with asymptomatic and symptomatic PHPT from the Indian PHPT registry.Material and methodsData of PHPT patients from the last 25 years (1995–2019) were analyzed for demographic, clinical presentation and biochemical measurements, and compared these characteristics between asymptomatic and symptomatic PHPT patients.ResultsOf the 554 patients, 54 (10%) patients had asymptomatic PHPT. There was a sharp rise in the proportion of asymptomatic PHPT patients of 3% in the first decade to 13% in the second decade of the century (p = 0.003). Patients with asymptomatic PHPT were significantly older (50 vs. 42 years; p < 0.0001) and had higher mean body mass index (27.8 vs. 23.5 kg/m2; p < 0.0001) compared to the symptomatic PHPT group. In addition, asymptomatic PHPT patients had significantly lower median plasma iPTH (180 vs. 370 pg/mL; p < 0.0001), serum alkaline phosphatase (119 vs. 172 IU/L; p < 0.0001), and parathyroid adenoma weight (1.0 vs. 2.62 g; p = 0.006) compared to the symptomatic PHPT group.ConclusionAlthough symptomatic PHPT is still most prevalent (> 90%) in India with higher indices of the disease and tumor weights, there is a progressive rise in the prevalence of asymptomatic PHPT patients in the last decade. Improvements in calcium and vitamin D nutrition might account for this change as in the Western series.

ObjectivesTo assess and compare the diagnostic accuracy of non-ophthalmologist-led diabetic retinopathy screening (DRS) at health and wellness centres (HWCs) and offline artificial intelligence (AI)-assisted community-based screening, using specialist grading as the reference standard in India.Design, settings and participantsPragmatic diagnostic accuracy study in primary healthcare settings. The settings included HWCs and community-based screening sites in rural Block Boothgarh, Mohali District, Punjab, India. A total of 600 people with diabetes aged ≥30 years were enrolled across three screening models: (1) non-ophthalmologist-led DRS at the HWC, (2) AI-assisted smartphone-based DRS in the community and (3) standard referral-based care. Retinal images were captured using non-mydriatic fundus cameras and independently graded by two masked human graders; a senior retina specialist resolved any disagreements. The AI was assessed for its ability to detect diabetic retinopathy (DR) and referable diabetic retinopathy (RDR). Diagnostic performance metrics were reported.ResultsThe non-ophthalmologist-led model demonstrated 86.4% sensitivity (95% CI 65.1% to 97.1%) and 94.3% specificity (95% CI 88.5% to 97.7%) for DR detection, with an ungradability rate of 8%. For RDR, sensitivity reached 95.8% (95% CI 78.9% to 99.9%) and specificity was 93.1% (95% CI 88.0% to 96.5%). The offline AI-assisted model achieved 93.3% sensitivity (95% CI 68.1% to 99.8%) and 85.1% specificity (95% CI 76.9% to 91.2%) for RDR, but with a higher ungradability rate (38%), mainly due to cataracts and poor image quality. Both approaches effectively identified referable cases; however, the non-ophthalmologist-led model demonstrated greater accuracy and operational feasibility.ConclusionsThis study demonstrates that non-ophthalmologist-led DRS at HWCs can enhance access to primary care. Offline AI-enabled screening demonstrates potential for community use but is currently limited by image quality and binary classification outputs. Integrating both approaches may strengthen DRS coverage in resource-limited settings.Clinical trials registry of IndiaCTRI/2022/10/046283.

Purpose: To assess the utility of pre-defined imaging biomarkers on optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy in determining visual and anatomical outcomes. Methods: In this prospective, non-randomized, and interventional study, 17 patients with treatment-naive DME were included. OCT biomarkers [size/reflectivity of cysts, disorganization of retinal inner layers, integrity of ellipsoid zone or external limiting membrane, subfoveal serous retinal detachment, hyper-reflective foci (HRF)] and OCTA [vascular density (VD), foveal avascular zone (FAZ), and total micro-aneurysms in superficial capillary plexus and deep capillary plexus (DCP)] were analyzed at baseline and after three monthly intravitreal anti-VEGF injections. Response was defined as a decrease of 10% or more in central macular thickness from the baseline after three injections. Results: 13/17 (76.47%) patients were categorized as responders to anti-VEGF therapy. Non-responders had significantly greater hyper-reflectivity of cysts (P = 0.015), larger cystic spaces (P = 0.023), and an increased number of HRF (P = 0.04) at baseline. On OCTA, non-responders showed larger FAZ in DCP (1.35 ± 0.21 versus 1.14 ± 0.28 mm2) (P = 0.042) and lower VD (61.17 ± 0.45 versus 62.73 ± 3.32) in DCP at baseline. At 3 months, the VD increased in responders (63.10 ± 3.42) compared to a decrease in non-responders (60.82 ± 1.13) (P = 0.032). Conclusions: Non-responders show a higher number of micro-aneurysms, larger FAZ, and lower VD in the DCP on OCTA and higher cyst hyper-reflectivity and HRF and larger cystic spaces on OCT imaging.

Inorganic phosphate is a vital constituent of cells and cell membranes, body fluids, and hard tissues. It is a major intracellular divalent anion, participates in many genetic, energy and intermediary metabolic pathways, and is important for bone health. Although we usually think of phosphate mostly in terms of its level in the serum, it is needed for many biological and structural functions of the body. Availability of adequate calcium and inorganic phosphate in the right proportions at the right place is essential for proper acquisition, biomineralization, and maintenance of mass and strength of the skeleton. The three specialized mineralized tissues, bones, teeth, and ossicles, differ from all other tissues in the human body because of their unique ability to mineralize, and the degree and process of mineralization in these tissues also differ to suit the specific functions: locomotion, chewing, and hearing, respectively. Biomineralization is a dynamic, complex, and lifelong process by which precipitations of inorganic calcium and inorganic phosphate divalent ions form biological hard tissues. Understanding the biomineralization process is important for the management of diseases caused by both defective and abnormal mineralization. Hypophosphatemia results in mineralization defects and osteomalacia, and hyperphosphatemia is implicated in abnormal excess calcification and/or ossification, but the exact mechanisms underlying these processes are not fully understood. In this review, we summarize available evidence on the role of phosphate in biomineralization. Other manuscripts in this issue of the journal deal with other relevant aspects of phosphate homeostasis, phosphate signaling and sensing, and disorders resulting from hypo- and hyperphosphatemic states.

Background: People with type 2 diabetes (T2D) are at high risk of fragility fractures; however, there are no randomized controlled trials evaluating the efficacy of anti-osteoporosis drugs as a primary pre-specified endpoint in T2D. Objectives: To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D. Design: Prospective, randomized, open, blinded endpoint clinical pilot trial. Methods: Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7–10%, eGFR ⩾45 mL/min/1.73 m2 and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture or bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽−2.5 and high FRAX score will be eligible for inclusion. Subjects with secondary causes of osteoporosis, prior exposure to bone-active therapies or history of use of glucocorticoids/pioglitazone/thiazides/canagliflozin will be excluded. Finally, eligible subjects will undergo estimation of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone turnover markers (BTMs) (total procollagen type I N-propeptide, β-CTX) along with trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of non-dominant hand and leg. After a 2-week run in phase, they will be randomized in a 1:1:1:1 ratio to receive yearly zoledronate, or biannually denosumab or daily teriparatide (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary endpoints will be change in areal BMD and frequency of incident fractures at 18 months. The secondary endpoints will be change in HR-pQCT parameters, TBS and BTMs at 18 months. Adverse events will be recorded for all randomized participants. Ethics: The study has been approved by the Institute Ethics Committee. Written informed consent will be obtained from each participant. Discussion: The trial is expected to provide information regarding optimal anti-osteoporotic therapy in people with T2D and bone fragility. Registration: Prospectively registered in Clinical Trial Registry of India (CTRI/2022/02/039978).