Hepatic Medicine : Evidence and Research最新文献

{"title":"Severe alcoholic hepatitis: current perspectives","authors":"C. Philips, P. Augustine, Praveen Kumar Yerol, S. Rajesh, P. Mahadevan","doi":"10.2147/HMER.S197933","DOIUrl":"https://doi.org/10.2147/HMER.S197933","url":null,"abstract":"Abstract Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as acute on chronic liver failure with worse prognosis in the presence of infections and higher grades of liver disease severity. The clinical scenario involves a patient with a recent history of heavy alcohol consumption within three months of presentation with jaundice and characteristic liver enzyme elevation pattern with coagulopathy, hepatic encephalopathy, variceal bleeding and sepsis that results in extrahepatic organ failures. Several liver disease severities and therapy response indicators are in clinical use. Even though not approved, the only recommended treatment option for patients with severe AH is corticosteroids, which is without long term survival benefit. Novel efficacious treatment options awaiting high-quality multi-center studies include liver transplantation (involves strict selection criteria), growth factor therapy and fecal microbiota transplantation. In this exhaustive review, we discuss the definitions, disease severity, histopathology, and treatment options – past, present, and future, in patients with severe alcoholic hepatitis.","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 1","pages":"97 - 108"},"PeriodicalIF":2.1,"publicationDate":"2019-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S197933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49271426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of a mesenchymal stem cell conditioned medium fraction on morphological characteristics of hepatocytes in acetaminophen-induced acute liver failure: a preliminary study","authors":"A. Temnov, K. Rogov, V. Zhalimov, P. Igor, S. Pekov, A. Bader, A. Sklifas, S. Giri","doi":"10.2147/HMER.S196354","DOIUrl":"https://doi.org/10.2147/HMER.S196354","url":null,"abstract":"Background: In our studies, it was shown that the effectiveness of the conditioned medium obtained by cultivating mesenchymal stem cells depends on the microenvironment conditions used to cultivate the cells. It was demonstrated that the conditioned medium obtained by culturing cells with low oxygen content (10%) has a much more pronounced protective effect. Methods: Protein compositions obtained from MSCs cultured under hypoxic (10% O2 hc-MSC) and normal (21% O2 nc-MSC) conditions were used to treat acute liver failure (ALF) induced in mice by acetaminophen injection. Thus, we obtained fractions normalized by volume, which predominantly contained proteins with masses > 50, 50-30, 30-10, and 10-3 kDa. Results: The data from biochemical studies have shown that only fractions from 10 to 30 kDa (hcMSC and ncMSC) significantly reduced the level of liver enzymes in the beginning of the acute period after acetaminophen administration. Mass spectrometry analysis of the proteins contained in the isolated fractions showed a sharp increase in the protein levels in the 10-30 kDa hcMSC fraction as compared with that in 10-30 kDa ncMSCs. The composition obtained from MSCs cultured at lower O2 level (fraction 10-30 kDa hcMSC) was shown to be more potent than the composition prepared from normoxic cells. Conclusion: The results have shown that a composition obtained by culturing the cells under a reduced content of O2 (10%), significantly improves the biochemical parameters, and histological arrester reduces the degree of inflammation and stimulates regenerative processes in liver, compared to both the control group and group treated with the composition that was obtained by culturing the cells under normal oxygen content.","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 1","pages":"89 - 96"},"PeriodicalIF":2.1,"publicationDate":"2019-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S196354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41988129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomal acid lipase deficiency - early diagnosis is the key.","authors":"Georg Strebinger,&nbsp;Elena Müller,&nbsp;Alexandra Feldman,&nbsp;Elmar Aigner","doi":"10.2147/HMER.S201630","DOIUrl":"https://doi.org/10.2147/HMER.S201630","url":null,"abstract":"<p><p>Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease that may present from infancy to late adulthood depending on residual enzyme activity. While the severe form manifests as a rapidly progressive disease with near universal mortality within the first 6 months of life, milder forms frequently go undiagnosed for prolonged periods and typically present with progressive fatty liver disease, enlarged spleen, atherogenic dyslipidemia and premature atherosclerosis. The adult variant of LAL-D is typically diagnosed late or even overlooked due to the unspecific nature of the presenting symptoms, which are similar to common changes observed in the context of the metabolic syndrome. This review is aimed at delineating clinically useful scenarios in which pediatric or adult medicine clinicians should be aware of LAL-D as a differential diagnosis for selected patients. This is particularly relevant as a potentially life-saving enzyme replacement therapy has become available and the diagnosis can easily be ruled out or confirmed using a dried blood spot test.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 ","pages":"79-88"},"PeriodicalIF":2.1,"publicationDate":"2019-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S201630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37344014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of direct-acting antiviral therapy for hepatitis C viral infection. Real-life experience in Bahrain.","authors":"Maheeba Abdulla,&nbsp;Hamed Ali,&nbsp;Hafsa Nass,&nbsp;Jawad Khamis,&nbsp;Jehad AlQamish","doi":"10.2147/HMER.S190967","DOIUrl":"https://doi.org/10.2147/HMER.S190967","url":null,"abstract":"<p><p><b>Purpose:</b> The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of chronic hepatitis C viral (HCV) infection. This study aims to establish real-world treatment efficacy of Sofosbuvir-based (SOF-B) and Ombitasvir/Paritaprevir/Ritonavir-based (OPR-B) regimens. <b>Patients and methods:</b> This prospective, non-randomized observational real-life study was conducted in Salmaniya Medical Complex, Bahrain, and included consecutive patients with chronic HCV infection (genotypes 1-4) who were treated with direct-acting antivirals. Sustained virologic response to therapy was assessed at week 12 post end of treatment (SVR12). <b>Results:</b> Of the 167 patients included, 60.5% (n=101) were treated with SOF-B and 39.5% (n=66) with OPR-B regimens for 12 weeks (n=148; 88.6%) or 24 weeks (n=19; 11.4%). SVR12 was achieved in 156 (93.4%) patients, 4 patients failed to achieve SVR despite completion of treatment, and 7 patients discontinued treatment due to non-compliance and were included in the analysis on an intention-to-treat basis. There was no difference between SOF-B and OPR-B regimens (95/101; 94.1%) and (61/66; 92.4%), respectively (<i>p</i>=0.68). However, SVR12 rates were significantly higher in patients without liver cirrhosis (103/104; 99.0%) compared to patients with cirrhosis (53/63; 84.1%; <i>p</i><0.001), and in patients who received 12-week-regimen (141/148; 95.3%) compared to those who received 24-week regimen (15/19; 78.9%; <i>p</i><0.024). However, logistic regression analysis identified cirrhosis at baseline to be the only independent predictor of non-SVR12 (OR: 16.1, 95% confidence interval 1.96-131.91, <i>p</i>=0.01). Apart from Hb, INR, and ALP, all other laboratory parameter improved following treatment (<i>p</i><0.05). <b>Conclusion:</b> Both SOF-B and OPR-B regimens achieved high SVR12 rates in this real-life cohort of patients with chronic HCV infection, similar to what is reported in other real-world studies. Cirrhosis was the only independent predictor of poor response.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 ","pages":"69-78"},"PeriodicalIF":2.1,"publicationDate":"2019-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S190967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37324532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the urinary metabolic profile of cholangiocarcinoma in a United Kingdom population.","authors":"Munirah Alsaleh, Thomas A Barbera, Helen L Reeves, Matthew E Cramp, Stephen Ryder, Hani Gabra, Kathryn Nash, Yi-Liang Shen, Elaine Holmes, Roger Williams, Simon D Taylor-Robinson","doi":"10.2147/HMER.S193996","DOIUrl":"10.2147/HMER.S193996","url":null,"abstract":"<p><p><b>Background:</b> Outside South-East Asia, most cases of cholangiocarcinoma (CCA) have an obscure etiology. There is often diagnostic uncertainty. Metabolomics using ultraperformance liquid chromatography mass spectrometry (UPLC-MS) offers the portent to distinguish disease-specific metabolic signatures. We aimed to define such a urinary metabolic signature in a patient cohort with sporadic CCA and investigate whether there were characteristic differences from those in patients with hepatocellular carcinoma (HCC), metastatic secondary liver cancer, pancreatic cancer and ovarian cancer (OCA). <b>Methods:</b> Spot urine specimens were obtained from 211 subjects in seven participating centers across the UK. Samples were collected from healthy controls and from patients with benign hepatic disease (gallstone, biliary strictures, sphincter of Oddi dysfunction and viral hepatitis) and patients with malignant conditions (HCC, pancreatic cancer, OCA and metastatic cancer in the liver). The spectral metabolite profiles were generated using a UPLC-MS detector and data were analyzed using multivariate and univariate statistical analyses. <b>Results:</b> The greatest class differences were seen between the metabolic profiles of disease-free controls compared to individuals with CCA with altered acylcarnitine, bile acid and purine levels. Individuals with benign strictures showed comparable urine profiles to patients with malignant bile duct lesions. The metabolic signatures of patients with bile duct tumors were distinguishable from patients with hepatocellular and ovarian tumors, but no difference was observed between CCA cases and patients with pancreatic cancer or hepatic secondary metastases. <b>Conclusion:</b> CCA causes subtle but detectable changes in the urine metabolic profiles. The findings point toward potential applications of metabonomics in early tumor detection. However, it is key to utilize both global and targeted metabonomics in a larger cohort for in-depth characterization of the urine metabolome in hepato-pancreato-biliary disease.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 ","pages":"47-67"},"PeriodicalIF":2.6,"publicationDate":"2019-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37266913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive impairment after liver transplantation: residual hepatic encephalopathy or posttransplant encephalopathy?","authors":"Linda Skibsted Kornerup, Henning Pflugrad, Karin Weissenborn, Hendrik Vilstrup, Gitte Dam","doi":"10.2147/HMER.S144667","DOIUrl":"10.2147/HMER.S144667","url":null,"abstract":"<p><p>Liver transplantation (LT) represents the definitive treatment for end-stage liver disease. Cognitive impairment following LT is frequent, referred to as postliver transplant encephalopathy (PLTE). LT removes the underlying chronic liver disease, and until recently hepatic encephalopathy (HE) was assumed to be fully reversible after LT. However, increasing evidence indicates that some degree of cognitive impairment may be present after LT. To which extent PLTE reflects cognitive impairment caused by residual HE (RHE) or the combined effect of other factors affecting brain function before, during, and after LT is not clarified. None of the available psychometric and neurophysiological tests used for detecting HE is shown to be able to distinguish between etiologies. The available, mostly retrospective, clinical studies indicate a high prevalence of abnormal psychometric tests after LT, and not all seem to recover completely. The patients with earlier HE show the most marked improvements, suggesting that the clinical picture of the early PLTE, in fact, represents RHE. Other early post-LT etiologies for PLTE comprise cerebral ischemia, critical illness encephalopathy, and immunosuppressive therapy. Late-onset etiologies comprise diabetes and hypertension, among others. PLTE regardless of etiology is a worrying issue and needs more attention in the form of mechanistic research, development of diagnostic/discriminative tools, and standardized prospective clinical studies.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 ","pages":"41-46"},"PeriodicalIF":2.6,"publicationDate":"2019-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/40/hmer-11-41.PMC6456244.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37201646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ombitasvir, paritaprevir, and ritonavir with peginterferon-α2a plus ribavirin in treatment-experienced patients with chronic hepatitis C virus genotype 1 infection.","authors":"David Bernstein,&nbsp;Rakesh Tripathi,&nbsp;Daniel E Cohen","doi":"10.2147/HMER.S189158","DOIUrl":"10.2147/HMER.S189158","url":null,"abstract":"<p><strong>Background: </strong>This international, phase 2, open-label, multicenter study (ClinicalTrials.gov Identifier: NCT01609933) was conducted to evaluate the safety and efficacy of an enhanced regimen consisting of the direct-acting antivirals (DAAs) ombitasvir, paritaprevir, and ritonavir administered for 24 weeks, combined with pegylated interferon-α2a plus ribavirin (pegIFN-α2a/RBV) for 48 weeks, in patients with chronic hepatitis C virus (HCV) genotype 1 infection who had experienced virologic failure with a prior DAA regimen. This study was undertaken at a time when options were limited for the retreatment of patients who had failed prior DAA therapy.</p><p><strong>Methods and results: </strong>Thirty-two patients were enrolled; the majority were male (78%) and White (94%), and the median age was 54.5 years. Twelve weeks after the last dose of study drug, sustained virologic response was achieved in 81.3% of patients. Five patients prematurely discontinued the study drugs and one patient relapsed. Safety and tolerability were similar to prior studies of pegIFN-α2a/RBV alone.</p><p><strong>Conclusion: </strong>Given the availability of highly efficacious DAA regimens that are both IFN- and RBV-free, this regimen is no longer relevant in today's HCV treatment landscape.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 ","pages":"35-40"},"PeriodicalIF":2.1,"publicationDate":"2019-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S189158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37045499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Portosystemic shunts and refractory hepatic encephalopathy: patient selection and current options.","authors":"Cyriac Abby Philips,&nbsp;Sasidharan Rajesh,&nbsp;Philip Augustine,&nbsp;Guruprasad Padsalgi,&nbsp;Rizwan Ahamed","doi":"10.2147/HMER.S169024","DOIUrl":"https://doi.org/10.2147/HMER.S169024","url":null,"abstract":"<p><p>Portosystemic shunt (PS) syndrome encompasses a spectrum of disease manifestations ranging from asymptomatic portal hypertension to recurrent and refractory hepatic encephalopathy, ultimately culminating in progressive hepatic failure in patients of cirrhosis and associated large PSs. PSs commonly seen in cirrhosis include splenorenal, gastrorenal, and dilated paraumbilical veins, all of which can present with recurrent or refractory hepatic encephalopathy. In this exhaustive review, we describe the anatomy of PSs, elucidate new theories on their pathophysiology, discuss the clinical implications of PSs in cirrhosis, provide details on different techniques (classical and novel) of shunt embolization, and explore all the pertinent current literature on shunt embolization for refractory and recurrent hepatic encephalopathy, all of which are enumerated with extensive images and illustrations.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 ","pages":"23-34"},"PeriodicalIF":2.1,"publicationDate":"2019-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S169024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36976134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous bacterial peritonitis in patients with cirrhosis: incidence, outcomes, and treatment strategies.","authors":"Sebastián Marciano, Juan Manuel Díaz, Melisa Dirchwolf, Adrián Gadano","doi":"10.2147/HMER.S164250","DOIUrl":"10.2147/HMER.S164250","url":null,"abstract":"<p><p>Spontaneous bacterial peritonitis is the most frequent bacterial infection in patients with cirrhosis. The reported incidence varies between 7% and 30% in hospitalized patients with cirrhosis and ascites, representing one of their main complications. Outcomes in patients with spontaneous bacterial peritonitis are poor since acute kidney injury, acute-on-chronic liver failure, and death occur in as much as 54%, 60%, and 40% of the patients, respectively, at midterm. Early antibiotic treatment of spontaneous bacterial peritonitis is crucial. However, the landscape of microbiological resistance is continuously changing, with an increasing spread of multidrug-resistant organisms that make its current management more challenging. Thus, the selection of the empirical antibiotic treatment should be guided by the severity and location where the infection was acquired, the risk factors for multidrug-resistant organisms, and the available information on the local expected bacteriology. The use of albumin as a complementary therapy for selected high-risk patients with spontaneous bacterial peritonitis is recommended in addition to antibiotics. Even though antibiotic prophylaxis has proven to be effective to prevent spontaneous bacterial peritonitis, a careful selection of high-risk candidates is crucial to avoid antibiotic overuse. In this article we review the pathogenesis, risk factors, and prognosis of spontaneous bacterial peritonitis, as well as the current evidence regarding its treatment and prophylaxis.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 ","pages":"13-22"},"PeriodicalIF":2.1,"publicationDate":"2019-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/54/hmer-11-013.PMC6336019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36926481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical steps to improve chronic hepatitis C treatment in people with opioid use disorder.","authors":"Carlos Roncero, Pablo Ryan, Richard Littlewood, Juan Macías, Juan Ruiz, Pedro Seijo, Raúl Felipe Palma-Álvarez, Pablo Vega","doi":"10.2147/HMER.S187133","DOIUrl":"10.2147/HMER.S187133","url":null,"abstract":"<p><strong>Objectives: </strong>People with a history of injecting drugs have high prevalence of hepatitis C virus (HCV) infection, and many have opioid use disorder (OUD). Modern HCV therapies with improved efficacy and tolerability are available, but access is often limited for this group, who may be underserved for health care and face social inequity. This work develops practical steps to improve HCV care in this population.</p><p><strong>Methods: </strong>Practical steps to improve HCV care in OUD populations were developed based on clinical experience from Spain, structured assessment of published evidence.</p><p><strong>Results: </strong>Options for improving care at engagement/screening stages include patient education programs, strong provider-patient relationship, peer support, and adoption of rapid effective screening tools. To facilitate work up/treatment, start options include simplified work up process, integration of HCV and OUD care, and continuous psychosocial support prior, during, and after HCV treatment.</p><p><strong>Conclusion: </strong>It is important to plan on local basis to set up a joint integrated approach between specific drug treatment services and local points of HCV care. The elements for a specific integrated program should be chosen from options identified, including education services, peer input, organization to make HCV screening and treatment easier by co-location of services, and wider access to prescribing direct-acting antiviral (DAA) therapy.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"11 ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2018-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/c9/hmer-11-001.PMC6307489.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36839011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}