Long-term clinical outcomes of extracorporeal shockwave lithotripsy in painful chronic calcific pancreatitis.

BACKGROUND: Long-term results of extracorporeal shockwave lithotripsy (ESWL) for large pancreatic duct (PD) stones in patients with idiopathic calcific pancreatitis (CP) are scanty. OBJECTIVE: To evaluate intermediate and long-term results of ESWL in a large cohort of patients with idiopathic CP. DESIGN: Cross-sectional study; retrospective chart review. SETTING: A high-volume, tertiary-care center for endoscopy and GI diseases. PATIENTS: A total of 636 patients with idiopathic CP who underwent ESWL and ERCP were followed-up. Patients were divided into intermediate (24-60 months) and long-term (>60 months) follow-up groups. INTERVENTION: ESWL and ERCP. MAIN OUTCOME MEASUREMENTS: Improvement in pain, analgesic use, hospitalization for pain, recurrence of calculi, need for additional intervention, and quality of life. RESULTS: A total of 636 of 1006 patients who underwent ESWL between 2004 and 2009 were followed for a maximum of 96 months. There were 364 patients in the intermediate follow-up group and 272 in the long-term follow-up group. After ESWL and ERCP, absence of pain was seen in 250 patients (68.7%), mild-to-moderate pain in 94 patients (25.4%), and severe pain in 20 patients (5.5%) of the intermediate group. In the long-term group, 164 patients (60.3%) had no pain, 97 patients (35.7%) had mild or moderate episodes of pain, whereas 11 patients (4.04%) had episodic severe pain. Recurrence of calculi was seen in 51 patients (14.01%) in the intermediate follow-up group and in 62 patients (22.8%) in the long-term group. Quality of life improved in a significant number of patients in both groups. LIMITATIONS: Retrospective study, single center, recall bias, and subjective pain and quality-of-life measurement scale. CONCLUSION: ESWL for large PD calculi offers good results in patients of idiopathic CP on intermediate and long-term follow-up.

A variant in TMPRSS2 is associated with decreased disease severity in COVID-19.

BACKGROUND: Mortality due to COVID-19 caused by SARS-CoV-2 infection varies among populations. Functional relevance of genetic variations in Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2), two crucial host factors for viral entry, might explain some of this variation. METHODS: In this comparative study in Indian subjects, we recruited 510 COVID-19 patients and retrieved DNA from 520 controls from a repository. Associations between variants in ACE2 and TMPRSS2 with disease severity were identified by whole exome sequencing (WES, n = 20) and targeted genotyping (n = 1010). Molecular dynamic simulations (MDS) were performed to explore functional relevance of the variants. Cleavage of spike glycoprotein by wild and variant TMPRSS2 was determined in HEK293T cells. Potential effects of confounders on the association between genotype and disease severity were tested (Mantel-Haenszel test). RESULTS: WES identified deleterious variant in TMPRSS2 (rs12329760, G > A, p. V160M). The minor allele frequency (MAF) was 0·27 in controls, 0·31 in asymptomatic, 0·21 in mild-to-moderately affected and 0·19 in severely affected COVID-19 patients. Risk of severity increased with decreasing MAF: Asymptomatic: Odds ratio-0·69 (95% CI-0·52-0·93; p = 0·01); mild-to-moderate: Odds ratio-1·89 (95% CI-1·22-2.92;p = 0·004) and severe: Odds ratio-1·79 (95% CI-1·11-2.88;p = 0·01). No confounding effect of diabetes and hypertension were observed on the risk of developing severe COVID-19 disease with respect to genotype. MDS revealed decreased stability of TMPRSS2 with 160 M variant. Spike glycoprotein cleavage by TMPRSS2 reduced ~2·4-fold in cells expressing 160 M variant. CONCLUSION: We demonstrate association of TMPRSS2 variant rs12329760 with decreased disease severity in COVID-19 patients from India.