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        Predictors of Early Readmissions in Hospitalized Patients With Gastroparesis: A Nationwide Analysis

        ( Ravi B Pavurala ),( Peter P Stanich ),( Somashekar G Krishna ),( Praveen Guturu ),( Alice Hinton ),( Darwin L Conwell ),( Gokulakrishnan Balasubramanian ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.3

        Background/Aims Gastroparesis is a chronic gastrointestinal disorder that frequently presents with symptoms that are difficult to manage, necessitating frequent hospitalizations. We sought to determine the predictors of early readmission due to gastroparesis based on etiology. Methods We identified all adults discharged with a principal diagnosis of gastroparesis after hospitalization from the 2014 Nationwide Readmission Database. We compared etiology wise (diabetes, post-surgical, and idiopathic) early readmission. Multivariate regression analyses were performed to identify significant predictors of 30-day readmission. Results A total of 12 689 patients were identified, 30.7% diabetic, 2.6% post-surgical, and 66.7% were idiopathic. Patients with diabetic gastroparesis were more likely to be readmitted within 30 days than idiopathic (adjusted odds ratio [aOR], 0.81; 95% confidence interval [CI], 0.69-0.94) and post-surgical gastroparesis (aOR, 0.58; 95% CI, 0.34-0.98). Pyloroplasty was associated with less likelihood of 30-day readmission (aOR, 0.45; 95% CI, 0.20-0.97). In addition, male gender (aOR, 1.18; 95% CI, 1.02-1.37), modified Elixhauser comorbidity score ≥ 3 (aOR, 1.38; 95% CI, 1.18-1.61), chronic pain syndrome (aOR, 1.41; 95% CI, 1.11-1.78), younger (18-64 years) age (aOR, 1.64; 95% CI, 1.34-2.00), need for percutaneous endoscopic gastrostomy/jejunostomy tube (aOR, 2.06; 95% CI, 1.21-3.52), and need for total parenteral nutrition (aOR, 1.70; 95% CI, 1.24-2.35) were associated with increased risk of 30-day readmission. Conclusions One in 5 patients was readmitted with gastroparesis within 30 days. In the diabetic group, diabetes-related complications contributed to readmissions than gastroparesis. Pyloroplasty is associated with reduced early hospital readmission. Prospective studies are needed for validation of these results. (J Neurogastroenterol Motil 2021;27:408-418)

      • Mechanisms of <i>CFTR</i> Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

        LaRusch, Jessica,Jung, Jinsei,General, Ignacio J.,Lewis, Michele D.,Park, Hyun Woo,Brand, Randall E.,Gelrud, Andres,Anderson, Michelle A.,Banks, Peter A.,Conwell, Darwin,Lawrence, Christopher,Romagnuo Public Library of Science 2014 PLoS genetics Vol.10 No.7

        <▼1><P>CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (<I>CFTR<SUP>sev</SUP></I>) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those <I>CFTR</I> mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (<I>CFTR<SUP>BD</SUP></I>) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate <I>CFTR<SUP>BD</SUP></I> mutations from among 81 previously described <I>CFTR</I> variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined <I>CFTR<SUP>BD</SUP></I> variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (<I>CFTR</I> R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, <I>CFTR<SUP>BD</SUP></I> increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by <I>CFTR<SUP>BD</SUP></I> variants through multiple mechanisms. <I>CFTR<SUP>BD</SUP></I> variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system.</P></▼1><▼2><P><B>Author Summary</B></P><P>Genetic disorders of ion channels can affect the body's ability to function properly in many ways. CFTR, an ion channel regulating movement of chloride and bicarbonate across cell membranes, is important for absorbing and secreting fluids. If the gene responsible for the CFTR channel is mutated severely, the result is cystic fibrosis, a hereditary disorder in which the patient develops thick mucus, especially in the lungs, as well as scarring (fibrosis) in the pancreas. Cystic fibrosis also affects the sweat glands, nasal sinuses, intestines, liver, and male reproductive system. Mutations to the CFTR gene that do not cause cystic fibrosis have been considered benign. However, we discovered 9 CFTR mutations that do not cause cystic fibrosis but do cause inflammation and scarring of the pancreas (chronic pancreatitis). These mutant CFTR channels secrete chloride, which is important in the sweat glands, lungs, and intestines, but not bicarbonate, which is important in the pancreas, sinuses, and male reproductive tract. We found patients with any of these 9 mutations had chronic pancreatitis, and often sinus infections, and male infertility, but not other symptoms of cystic fibrosis. Our computer models and data will help researchers develop better drugs and help physicians treating patients with chronic pancreatitis.</P></▼2>

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