Factors associated with unexplained sudden deaths among adults aged 18-45 years in India - A multicentric matched case-control study.

BACKGROUND OBJECTIVES: In view of anecdotal reports of sudden unexplained deaths in India's apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case-control study. METHODS: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI). RESULTS: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not. INTERPRETATION CONCLUSIONS: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death.

Overcoming Diagnostic Dilemma and Optimizing Intervention with Optical Coherence Tomographic Guidance in an Angiographically Ambiguous Renal Artery Stenosis Due to Fibromuscular Dysplasia.

With the advent of endovascular therapy, conventional angiography has replaced histology as a diagnostic gold standard for fibromuscular dysplasia (FMD). However, angiographic findings are not precisely diagnostic in isolated focal renal artery stenosis (RAS) in FMD. Optical coherence tomography (OCT) imaging by reflecting in vivo histology may improve the diagnostic accuracy in such cases. Restenosis following balloon angioplasty of RAS in FMD occurs frequently and often requires optimized reintervention. However, the role of OCT in the diagnostic evaluation of focal RAS in FMD and in optimizing the intervention is not well studied. We present a young female with resistant secondary hypertension due to bilateral focal RAS on angiography. In the absence of an angiographic string of beads appearance, the diagnoses remained uncertain. However, OCT imaging diagnosed a multifocal disease with characteristic changes of fibro-medial dysplasia, akin to its histological description in the literature. The patient underwent bilateral balloon angioplasty with good angiographic results. After one year on follow-up, relapse of uncontrolled systemic hypertension occurred due to bilateral restenosis. Despite a satisfactory repeat balloon angioplasty of the left-sided re-stenotic lesion, a significant residual pressure gradient persisted. Usage of OCT guided oversized balloon and stent safely achieved good results with complete resolution of the pressure gradient. Right renal artery stenosis required balloon angioplasty alone. She had complete resolution of hypertension without any medications at six months of follow-up. In conclusion, OCT can supplement other diagnostic modalities in providing a proper diagnosis in an angiographically ambiguous focal RAS in FMD. A persistent residual pressure gradient across the lesion despite good angiographic results may be optimized with OCT guidance during the intervention.

Neonatal Diabetes Mellitus: Novel Mutations.

OBJECTIVE: To describe the spectrum of neonatal diabetes mellitus (NDM), document new mutations, and review published Indian literature on the etiology of NDM. METHODS: Retrospective analysis of the clinical and genetic profile of 12 NDM patients. RESULTS: Eight patients presented with NDM before the age of 6 mo. Three other patients, including 2 siblings presented in later part of infancy. An additional patient was diagnosed at age 5 y with the same etiology as her infant sibling. Four patients had transient diabetes [TNDM:1 each with a mutation in KCNJ11 and INS gene, 2 with ABCC8 mutation], 7 had permanent diabetes [PNDM: 2 siblings with complete glucokinase deficiency, 2 siblings with thiamine responsive megaloblastic anemia (TRMA), 1 with Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome and 2 with Wolcott Rallison syndrome, (WRS)]. Four patients had 5 novel mutations. Genetic etiology could not be established in 1 patient with features of insulin resistance. Poorly controlled blood glucose in the TRMA patient led to hyperglycemia-induced hemichorea-hemiballismus, a rare manifestation in children. CONCLUSIONS: The authors describe 5 novel mutations, in the EIF2AK3, ABCC8, and GCK genes, a homozygous mutation at the ABCC8 locus presenting as TNDM, an obscure phenotype of the GCK gene mutation, and hyperglycemia-induced hemichorea-hemiballismus in a patient with TRMA. In India, PNDM is most commonly due to WRS similar to Middle Eastern countries with high consanguinity rates.

Elevated FGF23 in a patient with hypophosphatemic osteomalacia associated with neurofibromatosis type 1.

CONTEXT: The mechanism behind hypophosphatemia in the setting of neurofibromatosis type 1 (NF1) is not known. We describe a possible role of fibroblast growth factor-23 (FGF23) in the pathophysiology of hypophosphatemia in a patient with NF1. CASE DESCRIPTION: A 34-year woman with NF1 presented with severe hypophosphatemia, osteomalacia, and elevated plasma FGF23. The patient had considerable improvement on replacement of oral phosphate. Two Ga68 DOTANOC PET-CT scans over a period of 2 years failed to detect any localized uptake. Immuno-staining for FGF23 was absent in the neural-derived tumour cells of the neurofibromas in the proband. CONCLUSION: The patient with NF1 had elevated circulating FGF23. Tumour cells in the neurofibroma tissues did not stain for FGF23 on IHC. It is unlikely for neurofibromas to contribute to high circulating FGF23 levels in the proband.

Initial risk stratification and staging in prostate cancer with prostatic-specific membrane antigen positron emission tomography/computed tomography: A first-stop-shop.

Current imaging for prostate cancer (PCa) had limitations for risk stratification and staging. Magnetic resonance imaging frequently underestimated lymph node metastasis while bone scintigraphy often had diagnostic dilemmas. Prostatic-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has been remarkable in PCa recurrence. Ninety-seven PSMA PET-CT scans were reanalyzed for tumor node metastases staging and risk stratification of lymph node and distant metastasis proportion. Histopathology of 23/97 patients was available as gold standard. Chi-square test was used for proportion comparison. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), overestimation, underestimation, and correct estimation of T and N stages were calculated. Kappa coefficient (κ) was derived for inter-rater agreement. Lymph node or distant metastasis detection on PSMA PET/CT increased significantly with increase in risk category. PSMA PET/CT sensitivity, specificity, PPV, and NPV for extraprostatic extension, seminal vesicle invasion, and lymph node metastases were 63.16%, 100%, 100%, 36.36%; 55%, 100%, 100%, 25%; and 65.62%, 99.31%, 87.50%, and 97.53%, respectively. Kappa coefficient showed substantial agreement between PSMA PET/CT and histopathological lymph node metastases (κ = 0.734); however, it was just in fair agreement (κ = 0.277) with T stage. PSMA PET/CT overestimated, underestimated, and correct estimated T and N stages in 8.71%, 39.13%, 52.17% and 8.71%, 4.35%, and 86.96% cases, respectively. PSMA PET/CT has potential for initial risk stratification with reasonable correct N stage estimation, however underestimates T stage. Hence, we concluded that PSMA PET/CT should be used as " first-stop-shop" for staging and initial risk stratification of PCa with regional magnetic resonance imaging in surgically resectable cases.

Risk stratification and staging in prostate cancer with prostatic specific membrane antigen PET/CTObjective: A one-stop-shop.

OBJECTIVE: Current imaging modalities for prostate cancer (PC) had limitations for risk stratification and staging. Magnetic resonance imaging (MRI) frequently underestimated lymphatic metastasis while bone scintigraphy often had diagnostic dilemmas. Prostatic specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has been remarkable in diagnosing PC recurrence and staging. We hypothesized it can become one-stop-shop for initial risk stratification and staging. SUBJECTS AND METHOD: Ninety seven PSMA PET-CT studies were re analysed for tumor node metastases (TNM) staging and risk stratification of lymphatic and distant metastases proportion. The histopathology of 23/97 patients was available as gold standard. Chi-square test was used for proportion comparison. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), over-estimation, under-estimation and correct-estimation of T and N stages were calculated. Cohen's kappa coefficient (k) was derived for inter-rater agreement. RESULTS: Lymphic or distant metastases detection on PSMA PET/CT increased significantly with increase in risk category. PSMA PET/CT sensitivity, specificity, PPV and NPV for extra prostatic extension (EPE), seminal vesicle invasion (SVI) and lymphatic metastases were 63.16%, 100%, 100%, 36.36% & 55%, 100%, 100%, 25% and 65.62%, 99.31%, 87.50%, 97.53%, respectively. Cohen's kappa coefficient showed substantial agreement between PSMA PET/CT and histopathological lymphic metastases (κ 0.734) however, it was just in fair agreement (κ 0.277) with T stage. PSMA PET/CT over-estimated, under-estimated and correct-estimated T and N stages in 8.71%, 39.13%, 52.17% and 8.71%, 4.35%, 86.96% cases, respectively. CONCLUSION: We found that PSMA PET/CT has potential for initial risk stratifications with reasonable correct estimation for N stage. However, it can underestimate T stage. Hence, we suggest that PSMA PET/CT should be used for staging and initial risk stratification of PC as one-stop-shop with regional MRI in surgically resectable cases.

Antiulcer Activity of Ethanolic Extract of Salvadora indica (W.) Leaves on Albino Rats.

BACKGROUND: Ulcer can be developed inside the inner lining of the stomach (gastric ulcer) or the small intestine (duodenal ulcer). Both the ulcers are also cumulatively referred as peptic ulcers. It affects nearly 10% of world population. AIM: To investigate the antiulcer activity of ethanolic extract of Salvadora indica W. leaves (ESIL) on albino rats. MATERIALS AND METHODS: The present study was carried by pylorus ligation, ethanol and cysteamine induced ulcer models in albino rats. The antiulcer activity of ESIL (150, 300 and 600 mg/kg p.o. for 7 days) was compared with standard drugs (Ranitidine). In pyloric ligation induced ulcer model, the studied parameters were gastric volume, pH, total acidity, free acidity, and ulcer index whereas in ethanol and cysteamine induced ulcer model, the ulcer index was determined for severity of ulcers. The parameters studied were ulcer index, gastric juice volume, pH, free acidity and total acidity. RESULTS: In pyloric ligation model; the volume of gastric content, total/free acidity and pepsin activity was significantly decreased at p<0.05 and p<0.01 and pH of the gastric juice was significantly increased at p<0.05 and p<0.01 in ESIL treated groups as compared to control group. All the doses of ESIL showed dose dependent antiulcer effect as well as significant (p<0.05 and p<0.01) reduction in the ulcer index as compared to control group in all the experimental models. CONCLUSION: The results of the study indicate that the ESIL have better potential against ulcer which supports the traditional claims in folklore medicine.