{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:55:43Z","timestamp":1790016943921,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: To investigate the long-term efficacy of rifaximin (RFX) for hyperammonemia and efficacy for refractory ascites in patients with cirrhosis. Materials and Methods: We enrolled 112 patients with liver cirrhosis who were orally administered RFX in this study. Changes in the clinical data of patients were evaluated up to 36 months after RFX administration. The primary endpoint was a change in blood ammonia levels. Secondary endpoints included changes in clinical symptoms, Child\u2013Pugh (CP) score, number of hospitalizations, degree of refractory ascites, adverse events, and the relationship between RFX administration and the renin-angiotensin-aldosterone system. Results: An improved rate of overt hepatic encephalopathy (HE) of 82.7% was observed 3 months after RFX administration, which significantly induced a progressive decrease in blood ammonia concentration and an improved CP score up to 36 months. No serious RFX treatment-related adverse events were observed. 36.5% in patients after RFX administration improved refractory ascites. After RFX administration, patients with satisfactory control of hepatic ascites without addition of diuretic had lower renin concentration than those with poor control (p &lt; 0.01). At less than 41 pg\/mL renin concentration, the control of refractory ascites was significantly satisfactory (p &lt; 0.0001). Conclusions: RFX reduced blood ammonia concentration and improved hepatic spare ability and the quality of life of patients with long-term HE to up to 36 months. Our study revealed the effects of RFX against refractory ascites, suggesting that renin concentration may be a predictive marker for assessing ascites control.<\/jats:p>","DOI":"10.3390\/medicina58091276","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T23:16:36Z","timestamp":1663197396000},"page":"1276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Long-Term Effects of Rifaximin on Patients with Hepatic Encephalopathy: Its Possible Effects on the Improvement in the Blood Ammonia Concentration Levels, Hepatic Spare Ability and Refractory Ascites"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1320-6545","authenticated-orcid":false,"given":"Keiji","family":"Yokoyama","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-8326","authenticated-orcid":false,"given":"Ryo","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Higashi","sequence":"additional","affiliation":[{"name":"Higashi Hospital, 593-1 Hirotsu, Yositomi-machi, Chikujo-gun 871-0811, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Miyayama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomotaka","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotaro","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Umeda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0255-2904","authenticated-orcid":false,"given":"Kazuhide","family":"Takata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9310-1294","authenticated-orcid":false,"given":"Takashi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Shakado","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Sakisaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5493-5675","authenticated-orcid":false,"given":"Fumihito","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi 814-0180, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1746-6342.2006.03215.x","article-title":"Review article: The burden of hepatic encephalopathy","volume":"25","author":"Poordad","year":"2007","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/S1665-2681(19)32153-2","article-title":"Brain edema in acute liver failure. A window to the pathogenesis of hepatic encephalopathy","volume":"2","author":"Vaquero","year":"2003","journal-title":"Ann. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/s11938-006-0003-x","article-title":"Hepatic encephalopathy: A review of its pathophysiology and treatment","volume":"9","author":"Dbouk","year":"2006","journal-title":"Curr. Treat. Options Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/hep.24423","article-title":"Characterization of fecal microbial communities in patients with liver cirrhosis","volume":"54","author":"Chen","year":"2011","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature13568","article-title":"Alterations of the human gut microbiome in liver cirrhosis","volume":"513","author":"Qin","year":"2014","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/hep.27210","article-title":"Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver","volume":"60","author":"Vilstrup","year":"2014","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"American Association for the Study of Liver Diseases, and European Association for the Study of the Liver (2014). Hepatic encephalopathy in chronic liver disease: 2014 practice guidelines by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J. Hepatol., 61, 642\u2013659.","DOI":"10.1016\/j.jhep.2014.05.042"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1586\/14787210.3.2.201","article-title":"Rifaximin: A non-absorbable rifamycin antibiotic for use in non-systemic gastrointestinal infections","volume":"3","author":"Gerard","year":"2005","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1179\/joc.2008.20.2.186","article-title":"Effects of rifaximin on bacterial virulence mechanisms at supra- and sub-inhibitory concentrations","volume":"20","author":"Debbia","year":"2008","journal-title":"J. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000081991","article-title":"Rifaximin: In vitro and in vivo antibacterial activity\u2014A review","volume":"51","author":"Jiang","year":"2005","journal-title":"Chemotherapy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/hepr.13045","article-title":"Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II\/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial","volume":"48","author":"Suzuki","year":"2018","journal-title":"Hepatol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00535-021-01788-x","article-title":"Evidence-based clinical practice guidelines for Liver Cirrhosis 2020","volume":"56","author":"Yoshiji","year":"2021","journal-title":"J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/j.cgh.2013.12.021","article-title":"Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy","volume":"12","author":"Mullen","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1111\/apt.14275","article-title":"Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy","volume":"46","author":"Kang","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1097\/MEG.0000000000001311","article-title":"Long-term management of hepatic encephalopathy with lactulose and\/or rifaximin: A review of the evidence","volume":"31","author":"Hudson","year":"2019","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jgh.12070","article-title":"Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis","volume":"28","author":"Vlachogiannakos","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"531","DOI":"10.4254\/wjh.v11.i6.531","article-title":"Efficacy of long-term rifaximin treatment for hepatic encephalopathy in the Japanese","volume":"11","author":"Nishida","year":"2019","journal-title":"World J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.2169\/internalmedicine.5094-20","article-title":"Changes in the body composition and nutritional status after long-term rifaximin therapy for hyperammonemia in Japanese patients with hepatic encephalopathy","volume":"59","author":"Ishikawa","year":"2020","journal-title":"Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/hepr.13622","article-title":"Efficacy of rifaximin, a poorly absorbed rifamycin antimicrobial agent, for hepatic encephalopathy in Japanese patients","volume":"51","author":"Hiramine","year":"2021","journal-title":"Hepatol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1111\/hepr.13415","article-title":"Real-world effects of long-term rifaximin treatment for Japanese patients with hepatic encephalopathy","volume":"49","author":"Suzuki","year":"2019","journal-title":"Hepatol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s40273-018-0641-6","article-title":"Systematic review of the economic burden of overt hepatic encephalopathy and pharmacoeconomic impact of rifaximin","volume":"36","author":"Neff","year":"2018","journal-title":"Pharmacoeconomics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1756284819858256","DOI":"10.1177\/1756284819858256","article-title":"The efficacy and safety of rifaximin-\u03b1: A 2-year observational study of overt hepatic encephalopathy","volume":"12","author":"Oey","year":"2019","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1111\/jgh.13759","article-title":"Retrospective cross-sectional pilot study of rifaximin dosing for the prevention of recurrent hepatic encephalopathy","volume":"32","author":"Lyon","year":"2017","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.5604\/16652681.1226822","article-title":"Minimal hepatic encephalopathy in cirrhosis- how long to treat?","volume":"16","author":"Goyal","year":"2017","journal-title":"Ann. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/MEG.0000000000000786","article-title":"Improvement of sleep architecture parameters in cirrhotic patients with recurrent hepatic encephalopathy with the use of rifaximin","volume":"29","author":"Bruyneel","year":"2017","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_26","first-page":"42","article-title":"Comparison of rifaximin plus lactulose with the lactulose alone for the treatment of hepatic encephalopathy","volume":"65","author":"Ahire","year":"2017","journal-title":"J. Assoc. Physicians India"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3748\/wjg.v26.i2.199","article-title":"Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study","volume":"26","author":"Lv","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1097\/MEG.0000000000000743","article-title":"Rifaximin and midodrine improve clinical outcome in refractory ascites including renal function, weight loss and short-term survival","volume":"28","author":"Hanafy","year":"2016","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/hep.28898","article-title":"Rifaximin has no effect on hemodynamics in decompensated cirrhosis: A randomized, double-blind, placebo-controlled trial","volume":"65","author":"Kimer","year":"2017","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"702","DOI":"10.5009\/gnl16478","article-title":"Rifaximin and propranolol combination therapy is more effective than propranolol monotherapy for the reduction of portal pressure: An open randomized controlled pilot study","volume":"11","author":"Lim","year":"2017","journal-title":"Gut Liver"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1007\/s10620-016-4313-0","article-title":"Rifaximin decreases the incidence and severity of acute kidney injury and hepatorenal syndrome in cirrhosis","volume":"61","author":"Dong","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1002\/hep.1840080532","article-title":"Peripheral arterial vasodilation hypothesis: A proposal for the initiation of renal sodium and water retention in cirrhosis","volume":"8","author":"Schrier","year":"1988","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1080\/14017430802691528","article-title":"Cardiac and systemic haemodynamic complications of liver cirrhosis","volume":"43","author":"Henriksen","year":"2009","journal-title":"Scand. Cardiovasc. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/00365529950173726","article-title":"Nitrite and nitrate levels in patients with cirrhosis of the liver: Influence of kidney function and fasting state","volume":"34","author":"Heller","year":"1999","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0016-5085(00)70368-4","article-title":"Angiotensin II induces contraction and proliferation of human hepatic stellate cells","volume":"118","author":"Bataller","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.hepres.2005.01.017","article-title":"Expression of angiotensin II type one receptor in human cirrhotic livers: Its relation to fibrosis and portal hypertension","volume":"32","author":"Ikura","year":"2005","journal-title":"Hepatol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/jgh.13439","article-title":"Plasma renin concentration represents an independent risk factor for mortality and is associated with liver dysfunction in patients with cirrhosis","volume":"32","author":"Paternostro","year":"2017","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jhep.2010.03.013","article-title":"Renin-angiotensin-aldosterone inhibitors in the reduction of portal pressure: A systematic review and meta-analysis","volume":"53","author":"Tandon","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s12072-016-9705-x","article-title":"Renin-angiotensin system inhibitors and fibrosis in chronic liver disease: A systematic review","volume":"10","author":"Kim","year":"2016","journal-title":"Hepatol. Int."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pelusi, S., Petta, S., Rosso, C., Borroni, V., Fracanzani, A.L., Dongiovanni, P., Craxi, A., Bugianesi, E., Fargion, S., and Valenti, L. (2016). Renin-angiotensin system inhibitors, type 2 diabetes and fibrosis progression: An observational study in patients with nonalcoholic fatty liver disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163069"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1111\/hepr.12081","article-title":"Direct renin inhibitor, aliskiren, attenuates the progression of non-alcoholic steatohepatitis in the rat model","volume":"43","author":"Aihara","year":"2013","journal-title":"Hepatol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6705","DOI":"10.3748\/wjg.v23.i36.6705","article-title":"Serum angiotensin-converting enzyme level for evaluating significant fibrosis in chronic hepatitis B","volume":"23","author":"Noguchi","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8355","DOI":"10.3748\/wjg.v23.i47.8355","article-title":"Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity","volume":"23","author":"Kaji","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.cgh.2012.02.025","article-title":"Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites","volume":"10","author":"Kalambokis","year":"2012","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/hepr.13300","article-title":"Rifaximin-altered gut microbiota components associated with liver\/neuropsychological functions in patients with hepatic encephalopathy: An exploratory data analysis of phase II\/III clinical trials","volume":"49","author":"Kawaguchi","year":"2019","journal-title":"Hepatol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000494216","article-title":"Long-term effect of rifaximin with and without lactulose on the active bacterial assemblages in the proximal small bowel and faeces in patients with minimal hepatic encephalopathy","volume":"37","author":"Schulz","year":"2019","journal-title":"Dig. Dis."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/9\/1276\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:31:35Z","timestamp":1760142695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/9\/1276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,14]]},"references-count":46,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["medicina58091276"],"URL":"https:\/\/doi.org\/10.3390\/medicina58091276","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,14]]}}}