Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.

BACKGROUND: Actinium-225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. METHODS: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 (177Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival. FINDINGS: Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of 225Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225Ac-PSMA RLT. All patients who received more than seven cycles of 225Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded. INTERPRETATION: 225Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events. FUNDING: None.

Chemokine receptor CXCR4 based positron emission tomography imaging in systemic sclerosis-related interstitial lung disease.

OBJECTIVE: To assess chemokine receptor CXCR4 expression in lung parenchyma and on peripheral immune cells in systemic sclerosis-related interstitial lung disease (SSc-ILD) patients. METHODS: SSc-ILD patients underwent 68Ga- CPCR4 Trifluoroacetate positron emission tomography (PET) scan, SUVmean in different lung regions and architecturally abnormal areas, and receiver operating characteristic (ROC) curves were analyzed. CXCR4 expression on peripheral immune cells using flow cytometer was studied and correlated with the different lung regions. In addition, subset analysis of CXCR4 expression by clinical subset (early, progressive, stable), ILD pattern and anti-Scl-70 positivity were done. RESULTS: On PET, SSc-ILD patients showed higher median SUVmean uptake of CXCR4 in the whole lung (0.56; p< 0.0001), different lung regions and architecturally abnormal areas than controls. Highest area under curve (AUC) were observed in dorsobasal regions (AUC-0.91; p< 0.0001) and reticular with architecturally distorted areas (AUC-0.95; p< 0.0001). Progressive subset had higher whole lung median SUVmean (0.73) than early (0.49; p< 0.0001) and stable (0.45; p< 0.0001) subsets, and AUC than early and stable subsets. Usual interstitial pneumonia pattern ILD showed higher CXCR4 uptake compared with non-specific interstitial pneumonia (p= 0.0032). Additionally, a trend for higher uptake was noted in anti-Scl70 positive patients as compared with anti-Scl70 negative ones. SSc-ILD patients had higher CD4+CXCR4+T cells (p= 0.0003), and CD8+CXCR4+T cells (p= 0.0013), and showed moderate to strong association on correlation with the lung parenchymal regions. CONCLUSION: In SSc-ILD, CXCR4 expression is upregulated in both lung parenchyma and peripheral T cells, significantly in progressive and UIP subsets. CXCR4 expression is a potential tool for activity assessment and prognostication.

Incidentally detected diaphragmatic eventration as para-cardiac thoracic activity on myocardial perfusion imaging.

Diaphragmatic eventration is the elevation of hemi-diaphragm without any disruption to diaphragmatic continuity which can be congenital or acquired. The most common acquired cause is phrenic nerve paralysis due to traumatic causes and is usually incidentally diagnosed on chest radiograph or computed tomography. We hereby report a case of a patient who had road traffic accident with fracture of the left proximal femur. Stress Myocardial Perfusion Imaging (MPI) done for pre-operative clearance showed an incidental tracer avidity adjoining to left myocardium in the thorax. It was confirmed on anatomical imaging to be gastric cavity uptake due to diaphragm eventration.

Potential application of 68Ga-FAPI PET/CT for diagnosing cardiac sarcoidosis.

Detecting cardiac sarcoidosis; a potentially life-threatening condition is challenging and requires a multimodality imaging approach using echocardiography, PET/CT and CMR. Although 18F-FDG is the recommended PET tracer for evaluating cardiac sarcoidosis, it is limited by physiological cardiac FDG uptake and requires stringent patient preparation/ dietary modifications before imaging. We hereby present a case of cardiac sarcoidosis demonstrating myocardial FAPI uptake on cardiac PET, highlighting the potential role of 68Ga-FAPI PET in the evaluation of cardiac sarcoidosis.

Prevalence, risk factors and effect of curative parathyroidectomy on nephrocalcinosis in Asian-Indian patients with symptomatic primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is characterized by inappropriate secretion of parathyroid hormone, causing hypercalcemia and hypercalciuria, leading to renal stone diseases and nephrocalcinosis. The frequency, risk factors, and curative effect on nephrocalcinosis in post-parathyroidectomy have not been identified yet. Therefore, the present study evaluated the clinico-biochemical, radiological parameters and curative effect on nephrocalcinosis. A total of 583 PHPT patients were analysed in four groups viz. Group 1 (PHPT with nephrocalcinosis-98; 16.8%); Group 2 (PHPT with nephrolithiasis-227; 38.9%); Group 3 (PHPT with both nephrolithiasis and nephrocalcinosis-59; 10.1%); and Group 4 (PHPT without renal diseases-199, 34.1%). In the sub-group analysis, younger age (p ≤ 0.05), male gender (p ≤ 0.05), and hematuria (p ≤ 0.005) were significant in Group 1 vs. Group 4. Dysuria and low eGFR were significant in Group 1 vs. Group 2 (p ≤ 0.0005; p ≤ 0.05) and Group 1 vs. Group 4 (p ≤ 0.0005; p ≤ 0.0005). Polyuria (p ≤ 0.05; p ≤ 0.05, p ≤ 0.005), and gravluria (p ≤ 0.05; p ≤ 0.0005, p ≤ 0.005) were frequent in Group 1 vs. other groups. A significant difference was observed in S.Ca and, 24-hrs U.Ca in Group 1 vs. Group 2 {(12.2 (10.8-13.4) vs. 11.2 (10.7-12.4), p ≤ 0.05; 301 (189.5-465) vs. 180 (92.5-323.1), p ≤ 0.05} and Group 1 vs. Group 4 {(12.2 (10.8-13.4) vs. 11.4 (10.7-12.5), p ≤ 0.05 ; 301 (189.5-465) vs. 213 (110-360), p ≤ 0.0005}. Multivariate logistic regression showed gravluria [aOR = 9.2, p = 0.0001], S.Ca (aOR = 1.30, p = 0.003) and, 24-hrs U.Ca (aOR = 1.02, p = 0.042) to be independent predictors of nephrocalcinosis. Pre and post-operative assessment revealed decreased S. Ca levels [(11.9 ± 1.9) vs. (10.5 ± 1.0) mg/dL; p = 0.04] and complete radiological resolution (10.4%) in PHPT with nephrocalcinosis. Therefore, serum calcium, 24-hrs Urinary calcium, and gravluria were independent predictors of nephrocalcinosis with 10.4% showing complete radiological resolution post-operatively.

HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus-Based In Vivo Prediction in Humans: Part I.

Tolterodine tartrate (TOTA) is associated with adverse effect, high hepatic access, varied bioavailability, slight aqueous solubility, and short half-life after oral delivery. Hansen solubility parameters (HSP, HSPiP program), experimental solubility (T = 298.2 to 318.2 K and p = 0.1 MPa), computational (van't Hoff and Apelblat models), and thermodynamic models were used to the select solvent(s). HSPiP predicted PEG400 as the most suitable co-solvent based on HSP values (δd = 17.88, δp = 4.0, and δh = 8.8 of PEG400) and comparable to the drug (δd = 17.6, δp = 2.4, and δh = 4.6 of TOTA). The experimental mole fraction solubility of TOTA was maximum (xe = 0.0852) in PEG400 confirming the best fit of the prediction. The observed highest solubility was attributed to the δp and δh interacting forces. The activity coefficient (ϒi) was found to be increased with temperature. The higher values of r2 (linear regression coefficient) and low RMSD (root mean square deviation) indicated a good correlation between the generated "xe" data for crystalline TOTA and the explored models (modified Apelblat and van't Hoff models). TOTA solubility in "PEG400 + water mixture" was endothermic and entropy-driven. IR (immediate release product) formulation can be tailored using 60% PEG400 in buffer solution for 2 mg of TOTA in 0.25 mL (dosing volume). The isotonic binary solution was associated with a pH of 7.2 suitable for sub-Q delivery. The approach would be a promising alternative with ease of delivery to children and aged patients.

Genomic characterization of metastatic castration-resistant prostate cancer patients undergoing PSMA radioligand therapy: A single-center experience.

BACKGROUND: Genomic defects in DNA-damage repair (DDR) mechanisms have been proposed to affect the radiosensitivity of prostate cancers. In this study, we intended to evaluate the prevalence of genetic alterations in a cohort of metastatic castration-resistant prostate cancer (mCRPC) patients undergoing radioligand therapy (RLT) with prostate-specific membrane antigen (PSMA)-inhibitors as well as the impact of such mutations on treatment outcomes. METHODS: Data of consecutive mCRPC patients from 2017 to 2021 who were treated with PSMA-RLT and underwent next-generation sequencing (NGS) were collected and analyzed for response and survival outcomes. RESULTS: In 95 patients of mCRPC treated with PSMA-RLT, 15 patients (median age: 66 years, range: 50-73 years; [177 Lu]Lu-PSMA-617, n = 12; [225 Ac]Ac-PSMA-617, n = 3) underwent NGS. The median progression-free survival (PFS) of this cohort was 3 months (95% confidence interval: 1.6-4.4 months). On NGS, 21 genetic alterations were reported in 10/15 (67%) patients, of which 13 were DDR-associated alterations involving the genes: ATM (n = 3), BRCA2 (n = 3), TP53 (n = 2), PTEN (n = 2), FANCD2 (n = 1), FANCM (n = 1), and NBN (n = 1). Overall, 5/15 (33%) patients harbored six pathogenic variants (BRCA2, n = 2; ATM, n = 1; TP53, n = 1; PTEN, n = 2). No significant difference was noted for the biochemical response, radiological response, PFS, and overall survival between the patients with and without genetic alterations. CONCLUSIONS: Patients of mCRPC undergoing PSMA-RLT were frequently seen to harbor DDR-associated aberrations, albeit with no significant impact on treatment outcomes. Large prospective trials comparing PSMA-RLT-related outcomes in DDR-deficient and -proficient patients are required to bring out the differences, if any, in a more observable manner.

Water Induced Alterations in Self-Assembly of a Bio-Surfactant in Deep Eutectic Solvent for Enhanced Enzyme Activity.

Deep eutectic solvents (DESs) meet important requirements for green solvent technology, including non-toxicity, biodegradability, sustainability, and affordability. Despite possessing low cohesive energy density than water, DESs have been found to support the self-assembly of amphiphiles. It is very much pertinent to examine the effect of water on self-assembly of surfactants in DESs as the presence of water alters the inherent structure of DES, which is expected to affect the characteristic properties of self-assembly. Following this, we have investigated the self-assembly of amino-acid based surfactant, Sodium N-lauroyl sarcosinate (SLS), in DES-water mixtures (10, 30 and 50 w/w% of water) and explored the catalytic activity of Cytochrome-c (Cyt-c) in the formed colloidal systems. Investigations using surface tension, fluorescence, dynamic light scattering (DLS), and isothermal titration calorimetry (ITC) have shown that DES-water mixtures promote the aggregation of SLS, resulting in the lower critical aggregation concentration (cac ∼1.5-6-fold) of the surfactant as compared to water. The nanoclustering of DES at low water content and it's complete de-structuring at high water content affects the self-assembly in a contrasting manner governed by different set of interactions. Further, Cyt-c dispersed in DES-water colloidal solutions demonstrated 5-fold higher peroxidase activity than that observed in phosphate buffer.

Comparison of positional artifacts in myocardial perfusion imaging in supine and semi-reclining position using dedicated D-SPECT cardiac camera: validation using CT based attenuation correction.

BACKGROUND: Soft-tissue attenuation remains a major limitation of SPECT-MPI which interferes with the diagnosis of CAD. The current study aims to evaluate the pattern of attenuation artifacts in supine and semi-reclining positions on CZT cardiac camera and their interaction with gender, BMI and stress protocols. METHODS: We prospectively analysed 150 patients acquired in supine and semi-reclining positions on CZT camera. The images were evaluated for severity and extent of defect using 17-segment model. An additional CT scan was acquired to generate AC image in the first 50 patients studied to assist investigator learning for comparison of artifact vs true defects in the two SPECT systems. The defects present in one position or showing change in severity within two positions were considered as positional artifacts and further validated using CTAC supine image. RESULTS: In overall analysis, higher extent and severity of positional artifacts were observed more in semi-reclining position affecting the apex, apico-inferior, inferolateral and inferoseptal segments. Females showed more positional artifacts than males with inferior wall attenuation in the semireclining position and anterior wall attenuation in the supine position. A positive correlation of the extent and severity of positional artifacts was noted with an increasing BMI. In patients with BMI > 30, mid inferior and inferolateral segments were most affected followed by anterior wall segments. Highest correction of artifactual perfusion defects by CTAC was noted in inferior wall followed by inferolateral segments. CONCLUSION: The incidence of positional artifacts was greater in semi-reclining position in females, higher BMI groups and adenosine stress subsets. Knowledge of the pattern of positional artifacts appears to be a reliable alternative of CTAC for correct interpretation of myocardial perfusion images.

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial.

PURPOSE: Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients. METHODS: This was a randomized, parallel-group, open-label, phase 2, and non-inferiority trial. Chemotherapy-naïve patients with mCRPC and high PSMA-expressing lesions on 68 Ga-PSMA-11 PET/CT were randomly assigned in 1:1 ratio to 177Lu-PSMA-617 (6.0-7.4 GBq/cycle, every 8 weeks, up to 4 cycles) or docetaxel (75 mg/m2/cycle, every 3 weeks, up to 10 cycles). The primary end-point was best prostate-specific antigen response rate (PSA-RR), defined according to Prostate Cancer Clinical Trials Working Group-3 as proportion of patients achieving ≥ 50% decline in PSA from baseline. Non-inferiority margin of - 15% was pre-specified for PSA-RR. RESULTS: Between December 2019 and March 2021, 40 of the 45 patients assessed for eligibility underwent randomization. Fifteen of 20 patients in 177Lu-PSMA-617 arm and 20/20 patients in docetaxel arm received treatment per protocol. Of these, best PSA-RR in the 177Lu-PSMA-617 arm was 60% (9/15) versus 40% (8/20) in the docetaxel arm. The difference in the PSA-RRs between the two arms was 20% (95% confidence interval, CI: - 12-47, P = 0.25), meeting the pre-specified criterion for non-inferiority in per-protocol analysis. Further, progression-free survival rates at 6 months were 30% and 20% in the 177Lu-PSMA-617 and docetaxel arms respectively (difference 10%, 95% CI: - 18-38, P = 0.50). Overall, treatment-emergent grade ≥ 3 adverse events occurred less frequently with 177Lu-PSMA-617 than with docetaxel (6/20, 30% versus 10/20, 50%, respectively, P = 0.20). Quality-of-life outcomes improved significantly in 177Lu-PSMA-617 arm compared to docetaxel arm (P < 0.01). CONCLUSION: 177Lu-PSMA-617 was demonstrated to be safe and non-inferior to docetaxel in the treatment of mCRPC and could, thus, be potentially employed earlier in the disease course rather than being solely reserved for advanced end-stage disease. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India, CTRI/2019/12/022282.

Baseline renal dysfunction determines mortality following parathyroidectomy in primary hyperparathyroidism: analysis of Indian PHPT registry.

INTRODUCTION: Primary hyperparathyroidism (PHPT) in India is mostly symptomatic with renal and skeletal complications. Evidence on mortality outcomes following parathyroidectomy from India, where the disease is predominantly symptomatic is limited. MATERIAL AND METHODS: This was a prospective study to evaluate mortality outcomes in the Indian PHPT registry over the past 25 years (n = 464). Pre- and postoperative parameters and mortality data were obtained from medical records and/or by verbal autopsy, a method validated by WHO for data collection in settings where several deaths are noninstitutional. Patients were divided into survivor (SG) and nonsurvivor groups (NSG) to ascertain differences in presentation and the effect of parathyroidectomy. RESULTS: The overall mortality was 8.8% at a median follow-up of 8 years (IQR 1-13) after parathyroidectomy. Chronic kidney disease was the most common background cause of death (43.5%), followed by pancreatitis (28.2%). NSG had significantly more frequent renal dysfunction (91.9% vs 73.9%), anaemia (50 vs 16.6%) and pancreatitis (24.3 vs 6.4%). PTH (61.9 vs 38.3 pmol/l) and baseline creatinine (97.2 vs 70.7 µmol/l) were significantly higher and eGFR lower (66.7 vs 90.7 ml/min/1.73m2) in the NSG than SG. By Cox proportional modelling, renal dysfunction [HR 2.88 (1.42-5.84)], anaemia [HR 2.45 (1.11-5.42)] and pancreatitis [HR 2.65 (1.24-5.66)] on univariate and renal dysfunction [HR 3.33 (1.13-9.77)] on multivariate analysis were significant for mortality. Survival curves demonstrated a significantly higher mortality with lower eGFR values. CONCLUSIONS: Nonsurvivors in PHPT had greater prevalence and more severe baseline renal dysfunction than survivors. Survival after parathyroidectomy was significantly associated with estimated glomerular filtration rate at baseline.

18F-NaF PET uptake characteristics of coronary artery culprit lesions in a cohort of patients of acute coronary syndrome with ST-elevation myocardial infarction and chronic stable angina: A hybrid fluoride PET/CTCA study.

BACKGROUND: 18F-NaF PET/CT identifies high-risk plaques due to active calcification in coronary arteries with potential to characterize plaques in ST-elevation myocardial infarction (MI) and chronic stable angina (CSA) patients. METHODS: Twenty-four MI and 17 CSA patients were evaluated with 18F-NaF PET/CTCA for SUVmax and TBR values of culprit and non-culprit plaques in both groups (inter-group and intra-group comparison), and pre- and post-interventional MI plaques sub-analysis. RESULTS: Culprit plaques in MI patients had significantly higher SUVmax (1.6; IQR 0.6 vs 1.3; IQR 0.3, P = 0.03) and TBR (1.4; IQR 0.6 vs 1.1; IQR 0.4, P = 0.006) than culprit plaques of CSA. Pre-interventional culprit plaques of MI group (n = 11) revealed higher SUVmax (P = 0.007) and TBR (P = 0.008) values than culprit CSA plaques. Culprit plaques showed significantly higher SUVmax (P = 0.006) and TBR (P = 0.0003) than non-culprit plaques in MI group, but without significant difference between culprit and non-culprit plaques in CSA group. With median TBR cutoff value of 1.4 in MI culprit plaques, 6/7 plaques (85.7%) among the event prone non-culprit lesions had TBR values > 1.4 in CSA group. CONCLUSION: The study shows higher SUVmax and TBR values in MI culprit plaques and comparable TBR values for event prone plaques of CSA group in identifying high-risk plaques.

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry.

OBJECTIVE: To describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index-matched patients with PHPT without T2DM (in 1:2 ratio). RESULTS: Of the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06). CONCLUSION: The prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.

A detailed appraisal of renal manifestations in primary hyperparathyroidism from Indian PHPT registry: Before and after curative parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a systemic disorder characterized by hypercalcaemia and inappropriately elevated parathyroid hormone (PTH). Renal manifestations are one of the main presenting features both in symptomatic and asymptomatic PHPT patients. OBJECTIVES: We aimed to compare demographic, clinical and biochemical parameters of PHPT patients with and without renal manifestations and also analysed the influence of curative parathyroidectomy on renal functions. METHODS: We retrospectively analysed the data of PHPT patients from the last 25 years (1995- March 2019) and compared the demographic and clinical presentation and biochemical measurements between patients with and without renal manifestations and evaluated the changes in renal functions after 1 year of curative parathyroidectomy. RESULTS: Of the total 544 PHPT patients, 299 (55%) including 91 out of 141 (65%) males had renal manifestations. Among renal manifestations, nephrolithiasis and nephrocalcinosis were found in 41.7% and 27.6% PHPT patients, respectively. PHPT patients with renal manifestations had significantly higher creatinine (109.7 vs 79.6 µmol/L; P < .0001) and lower eGFR level (78.8 vs 93.9 mL/min/1.73 m2 ; P < .0001) compared to patients without renal manifestations. Parathyroidectomy resolved the clinical symptoms with biochemical cure in the patients from both the groups. Patients with renal manifestations showed improvement in creatinine and eGFR levels after 1 year of curative parathyroidectomy; however, patients without renal manifestations showed no change in creatinine and eGFR levels. CONCLUSION: Young age and male gender are predictors of renal manifestations in PHPT. Curative parathyroidectomy improves renal functions in PHPT patients with renal manifestations compared to PHPT patients without renal manifestation.

Progressive rise in the prevalence of asymptomatic primary hyperparathyroidism in India: Data from PHPT registry.

INTRODUCTION: Primary 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 METHODS: Data 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. RESULTS: Of 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. CONCLUSION: Although 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.

Cystic Parathyroid Adenomas: An Enigmatic Entity and Role of Tc-99 m Sestamibi Scintigraphy.

OBJECTIVE: Functional cystic lesion of the parathyroid gland is a rare cause of primary hyperparathyroidism (PHPT). They have been postulated to arise from the hemorrhage and cystic degeneration in the parathyroid adenoma (PA). We intended to analyze their scintigraphic and histopathological findings since available literature is sparse. METHODS: Dual-phase 99 mTc-sestamibi planar and SPECT/CT scans performed from January 2014 to January 2020 in patients presenting with PHPT were retrospectively analyzed. The clinical, biochemical, and ultrasound features were collected. Planar and SPECT/CT imaging parameters were analyzed. Detailed histopathological analysis, along with post-surgical clinical and biochemical features of the patients who underwent surgery, was reviewed with a mean follow-up of 21.8 ± 20.1 months. RESULTS: Of the 979 scans analyzed, 10 showed cystic parathyroid lesions (M:F- 3:7, mean age 45.6 ± 15 years, range: 23-66). The predominant presenting features in patients were abdominal pain and renal stone disease, present in 60% of the patients. On planar scintigraphy, 90% of the patients had tracer avid distinct lesions, whereas tracer activity was seen in the solid part of the cystic lesions in all 10 patients on SPECT/CT, with cystic areas showing an attenuation of 23.1 ± 7.6 HU. Eight of these patients underwent surgery, with all showing PA with cystic changes on histopathology. Two of these patients also showed hemorrhage within the cystic spaces. CONCLUSION: Hemorrhage within a PA may give rise to cystic parathyroid lesions with PHPT. 99 mTc-sestamibi scintigraphy with dual-phase imaging and SPECT/CT may help in detecting this rare entity.

Parathyroid Carcinoma: An Experience from the Indian Primary Hyperparathyroidism Registry.

OBJECTIVE: To describe the details of widely invasive parathyroid carcinoma (WIPC) patients admitted in the Endocrinology department of our institute during the last 22 years and to compare their clinical, biochemical, and hormonal profile with minimally invasive parathyroid carcinoma (MIPC) and sporadic parathyroid adenoma patients. METHODS: This is a retrospective analysis of data from the Indian primary hyperparathyroidism registry. RESULTS: Of the 547 primary hyperparathyroidism patients in the registry, 5 (2 men and 3 women) had WIPC (0.9%) and 7 (1 man and 6 women) had MIPC (1.3%), with median ages of 45 (interquartile range, 41-51) years and 47 (interquartile range, 28-48) years, respectively. Among the patients with WIPC, renal manifestations were present in 5 patients, skeletal manifestations in 4 patients, and palpable neck masses in 4 patients. Three patients had distant metastases and 2 had cervical lymph node involvement. All 5 patients had surgical resection of their cancers, with persistent disease in 4 patients, but all patients died within 2 years after surgery. One patient with MIPC had a palpable parathyroid nodule; none had lymph nodal or distant metastases. None of the patients with MIPC died during the median follow-up of 18 (interquartile range, 12-18) months. Patients with WIPC had significantly higher serum calcium level compared with sporadic parathyroid adenoma patients with skeletal and renal manifestations. CONCLUSION: Accurate histopathologic classification of parathyroid carcinoma is important as WIPC is associated with a more aggressive clinical course and a higher risk of mortality than MIPC.

Endovascular stenting with a drug-eluting stent of transplanted renal artery stenosis in a dual kidney transplanted patient.

Renal transplant remains the preferred therapy for end-stage renal disease (ESRD). Given the shortage of suitable donor kidneys, use of an expanded criteria donor (ECD) allows marginal kidneys to be transplanted; albeit at risk of increased graft failure due to lower nephron mass. To reduce the risk of graft failure, double kidney transplant (DKT) is advocated, with favorable outcomes. Transplant renal artery stenosis (TRAS) is one of the most common vascular complications following renal transplant. Unlike single kidney transplants, where TRAS usually presents with fluid overload, uncontrolled hypertension, and worsening kidney functions; it may be clinically silent in DKT patients since they have two functional transplanted kidneys. We hereby report a case of TRAS in a DKT patient who had 2 years of favorable clinical outcomes following successful endovascular stenting. He however recently died of COVID-19 associated pneumonitis.

O transplante renal continua sendo a terapia preferida para doenças renais em fase terminal. Dada a escassez de rins de doadores adequados, o doador com critérios expandidos permite que rins marginais sejam transplantados, embora haja um maior risco de falha do enxerto devido à diminuição da massa nefrótica. Para diminuir o risco de falha do enxerto, recomenda-se o transplante renal duplo (TRD), com resultados favoráveis. A estenose de artéria renal transplantada (EART) é uma das complicações vasculares mais comuns após o transplante renal. Ao contrário dos transplantes de rim simples, nos quais a EART geralmente se manifesta como sobrecarga de fluido, hipertensão descontrolada e piora das funções renais, ela pode ser clinicamente silenciosa em pacientes com TRD, pois eles têm dois rins funcionais transplantados. Relatamos aqui um caso de EART em um paciente com TRD que teve resultados clínicos favoráveis por dois anos após o sucesso do implante de stent endovascular. No entanto, ele morreu recentemente de pneumonite associada à covid-19.

Weight gain after curative parathyroidectomy predicts increase in bone mineral density in patients with symptomatic primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) results in reduction of bone mineral density (BMD) and an increased risk of pathological fractures. Curative surgery does improve BMD; however, the magnitude of rise and predictive factors are highly variable amongst the hitherto available studies. OBJECTIVES: To quantify the magnitude of improvement in BMD after curative surgery in patients with symptomatic PHPT and dissect out the possible clinical and biochemical parameters predicting the BMD rise. METHODS: We conducted a retrospective study of symptomatic PHPT patients undergoing surgery between August 2016 and July 2018. Patients achieving biochemical cure with pre- and post-operative (at least 1 year after surgery) dual-energy X-ray absorptiometry scans performed were included in the study. RESULTS: After exclusion, 63 patients were included in the study (M:F = 2:5; mean age = 44.8 years). At a median interval of 15 months, the median per cent change in BMD (ΔBMD) at lumbar spine (LS), total hip (TH), femoral neck (FN) and one-third distal radius (forearm) was 6.5%, 7.0%, 8.1% and 6.9%, respectively. Following multiple linear regression analysis, baseline BMD was found to inversely predict ΔBMD at LS, TH and forearm. Pre-operative iPTH positively predicted ΔBMD at LS and FN. Interestingly, 82.5% of the patients had a gain in body weight following curative surgery and change in body weight emerged as a significant positive predictor of ΔBMD at all sites. CONCLUSIONS: Curative surgery improves BMD at all sites in patients with symptomatic PHPT. Weight gain following surgery can be used as a positive clinical predictor of BMD rise.

Prevalence of antiphospholipid antibodies in patients with overt myocardial dysfunction in systemic lupus erythematosus. A case-control study.

BACKGROUND: Small case-series have reported overt myocardial dysfunction to be associated with positive antiphospholipid antibodies in patients of systemic lupus erythematosus (SLE). However, there is no case-control study that has examined this association. METHODS: This case-control study recruited patients of SLE (fulfilling SLICC criteria) with overt myocardial dysfunction as cases and those without this as controls. Overt myocardial dysfunction was defined by echocardiography as global left ventricular dysfunction and reduced ejection fraction (<50%). Those patients with a prior diagnosis of anti-phospholipid antibody syndrome, coronary artery disease, rheumatic heart disease or severe pulmonary artery hypertension were excluded. Antibodies tested included lupus anticoagulant, anticardiolipin antibodies (IgM and IgG) and anti-beta 2 glycoprotein 1 antibodies (IgM and IgG). Patients with positive tests underwent repeat testing for persistent positivity after 12 weeks. RESULTS: This study included 51 patients (21 cases and 30 controls) having a mean (SD) age of 33 (13.3) years, and disease duration (median, IQR) of 28 months (12-38 months). The mean ejection fraction of cases was 31.7 (9.3)% while that of controls was 55.7 (1.7)% (p = 0.03). The frequency (percentage) of positive antiphospholipid antibodies was not significantly different between cases and controls (43%, 40%, p = 0.8). The frequency (percentage) of anti-cardiolipin antibody was also not significant between the groups (38%, 37%, p = 0.57). Serositis and leucopenia were more prevalent in SLE patients with myocardial dysfunction (p = 0.005). CONCLUSION: This study did not find any significant association of anti-phospholipid antibodies with overt myocardial dysfunction in patients of SLE.