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1.
Scand J Clin Lab Invest ; 81(4): 324-331, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33794701

ABSTRACT

Several diseases have a deleterious fibrosis component. Biomarkers indicating potential clinical utility that reliably reflect the degree of fibrosis have been introduced, one of them being soluble suppression of tumorigenicity 2 (sST2). The aim of our study was to explore the association of cardiometabolic risk factors, different diseases and total mortality with biomarker sST2 and see, how fibrosis is portrayed in these conditions. In addition, we were interested to see if sST2 levels could predict fibrosis in the long-term (21 years). The Oulu Project Elucidating Risk of Atherosclerosis (OPERA) survey collected data on the same individuals in years 1991-1993 (baseline, n = 1045), 2013-2014 (follow-up, n = 600) and mortality data until year 2019. Smoking at baseline retained a significant association with sST2 levels reflecting fibrosis development 20 years later. In the multivariate model male gender, diabetes, quick-index, levels of alanine aminotransferase (ALAT), high-density lipoprotein (HDL) cholesterol and high-sensitivity C-reactive protein (hsCRP) were associated with elevated sST2 levels at the examination 2013-2014. sST2 levels were higher among subjects suffering from cardiovascular disease (p = .031), cancer (p = .021), mild cognitive decline (p = .046) and diabetes (p < .001). Total mortality was assessed by using the Cox proportional hazard survival model analysis. sST2 (log-transformed) was an independent predictor of total mortality (HR 9.4; 95% CI 2.8-31.4, p<.001) when age, gender, diabetes, smoking, quick-index, levels of ALAT, HDL-cholesterol and hsCRP were added as covariates. In addition, elevated levels indicated worse prognosis and predicted mortality.


Subject(s)
Biomarkers/blood , Fibrosis/blood , Interleukin-1 Receptor-Like 1 Protein/blood , Adult , Aged , Aged, 80 and over , Atherosclerosis/blood , Atherosclerosis/mortality , Cardiovascular Diseases/blood , Cardiovascular Diseases/mortality , Chronic Disease , Female , Fibrosis/mortality , Glucose Tolerance Test , Humans , Male , Middle Aged , Mortality , Neoplasms/blood , Neoplasms/mortality , Risk Factors , Solubility
2.
Am J Gastroenterol ; 115(8): 1210-1216, 2020 08.
Article in English | MEDLINE | ID: mdl-32467506

ABSTRACT

INTRODUCTION: There is increasing recognition of the central role of muscle mass in predicting clinical outcomes in patients with liver disease. Muscle size can be extracted from computed tomography (CT) scans, but clinical implementation will require increased automation. We hypothesize that we can achieve this by using artificial intelligence. METHODS: Using deep convolutional neural networks, we trained an algorithm on the Reference Analytic Morphomics Population (n = 5,268) and validated the automated methodology in an external cohort of adult kidney donors with a noncontrast CT scan (n = 1,655). To test the clinical usefulness, we examined its ability to predict clinical outcomes in a prospectively followed cohort of patients with clinically diagnosed cirrhosis (n = 254). RESULTS: Between the manual and automated methodologies, we found excellent inter-rater agreement with an intraclass correlation coefficient of 0.957 (confidence interval 0.953-0.961, P < 0.0001) in the adult kidney donor cohort. The calculated dice similarity coefficient was 0.932 ± 0.042, suggesting excellent spatial overlap between manual and automated methodologies. To assess the clinical usefulness, we examined its ability to predict clinical outcomes in a cirrhosis cohort and found that automated psoas muscle index was independently associated with mortality after adjusting for age, gender, and child's classification (P < 0.001). DISCUSSION: We demonstrated that deep learning techniques can allow for automation of muscle measurements on clinical CT scans in a diseased cohort. These automated psoas size measurements were predictive of mortality in patients with cirrhosis showing proof of principal that this methodology may allow for wider implementation in the clinical arena.


Subject(s)
Deep Learning , Fibrosis/mortality , Muscle, Skeletal/diagnostic imaging , Adolescent , Adult , Aged , Algorithms , Cohort Studies , Female , Humans , Male , Michigan , Middle Aged , Predictive Value of Tests , Prospective Studies , Tomography, X-Ray Computed , Young Adult
3.
Clin Chim Acta ; 505: 141-147, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32119835

ABSTRACT

BACKGROUND: Previous studies have used a modified version of the Child-Turcotte-Pugh (CTP) score to include insulin-like growth factor 1 (IGF-1) concentrations, denoted the Insulin-like Growth Factor 1-Child-Turcotte-Pugh (IGF-CTP) system. We evaluated the predictive power of IGF-CTP for 1-year mortality in patients with decompensated cirrhosis (DC). METHODS: A total of 386 patients with DC were retrospectively analyzed. Comparison of distribution of patients with decompensated cirrhosis according to Insulin-like Growth Factor-1-Child-Turcotte-Pugh and Child-Turcotte-Pugh scores were performed. Area under the receiver operating characteristic curves (AUROCs) for IGF-CTP, CTP and the Model for End-stage Liver Disease (MELD) scores were evaluated to compare predictive value. Univariate and multivariate analyses were carried out to determine potential risk factors for 1-y mortality. RESULTS: During the 1-y follow-up, 94 patients died. Significantly more patients (both surviving and non-surviving) were classified as IGF-CTP stage C than CTP stage C. The AUROC of IGF-CTP was significantly higher than that of CTP and MELD in the training and validation cohorts. Multivariate analysis indicated IGF-CTP score and IGF-1 to be independently associated with mortality. CONCLUSION: The IGF-CTP score is independently associated with mortality for patients with DC, and offers more accurate prediction of 1-y mortality than either CTP or MELD score for these patients.


Subject(s)
Algorithms , Fibrosis/blood , Insulin-Like Growth Factor I/analysis , Adult , Aged , Area Under Curve , Cohort Studies , End Stage Liver Disease/blood , Female , Fibrosis/mortality , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Factors , Survival Analysis
5.
Hepatol Int ; 14(2): 281-287, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31468295

ABSTRACT

AIMS: Non-cirrhotic portal fibrosis (NCPF) is a rare cause of pediatric portal hypertension. There is abundant literature in adults but paucity of data in children. We aimed to evaluate and compare the endoscopic and long-term outcomes of children with NCPF. METHODS: Consecutive children (≤ 18 years) diagnosed with NCPF evaluated for clinical and endoscopic profile and outcome. The cohort underwent 3 weekly endoscopic sessions until esophageal variceal eradication followed by 6-12 monthly endoscopic surveillance. Non-bleeders and bleeders were compared for endoscopic outcome. RESULTS: Forty-five NCPF children with median age of 14.5 (6-18) years and symptom duration 12 (1-120) months presented with spleen-related issues (78%), esophageal varices (96%), primary gastric varices (56%), and portal hypertensive gastropathy (89%). Thirty-three patients undergoing endotherapy (secondary prophylaxis n = 22, primary prophylaxis n = 11) showed primary eradication of varices after 5 (2-12) sessions. 36% showed recurrence of esophageal varices in 11 (6-42) months and secondary gastric varices developed in 12%. Overall 87% patients required endoscopic intervention at onset or follow-up. Poor outcome was observed in ten patients (n = 9 bleeders). Three children died of variceal bleeding before endoscopic eradication of esophageal varices. Three developed decompensation after a median follow-up of 48 (3-120) months and referred for liver transplantation. Four patients required surgery for portal hypertension. CONCLUSIONS: Overall, endoscopic outcome of NCPF is favorable. One-third patients have recurrence of esophageal varices. Small proportion of bleeders have poor outcome.


Subject(s)
Esophageal and Gastric Varices/therapy , Fibrosis/therapy , Portal System , Adolescent , Child , Child Health Services , Esophageal and Gastric Varices/mortality , Esophagoscopy , Female , Fibrosis/mortality , Humans , India , Male , Recurrence , Sclerotherapy , Survival Analysis , Treatment Outcome
6.
Respir Res ; 20(1): 271, 2019 Dec 03.
Article in English | MEDLINE | ID: mdl-31796019

ABSTRACT

BACKGROUND: All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. METHODS: Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. RESULTS: Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5-1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1-143.8; P < 0.001). The bronchiectasis group had higher all-cause (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.09-1.47), respiratory (aHR, 3.49; 95% CI, 2.21-5.51), and lung cancer-related (aHR, 3.48; 95% CI, 2.33-5.22) mortality risks than the control group. In subgroup analysis, patients with airflow limitation and ever smokers showed higher all-cause mortality risk among bronchiectasis patients. Therefore, we observed significant interrelation between bronchiectasis and smoking, concerning the risks of all-cause mortality (P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097-0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631-15.736). CONCLUSION: Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers.


Subject(s)
Bronchiectasis/diagnostic imaging , Bronchiectasis/mortality , Cause of Death , Lung Neoplasms/mortality , Adult , Bronchiectasis/pathology , Case-Control Studies , Cystic Fibrosis , Female , Fibrosis/mortality , Fibrosis/pathology , Hospitals, University , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Middle Aged , Proportional Hazards Models , Radiography, Thoracic/methods , Reference Values , Republic of Korea , Respiratory Function Tests , Retrospective Studies , Risk Assessment , Severity of Illness Index , Survival Analysis , Tomography, X-Ray Computed/methods , Young Adult
7.
United European Gastroenterol J ; 7(8): 1124-1134, 2019 10.
Article in English | MEDLINE | ID: mdl-31662869

ABSTRACT

Background: Fibrosis is deemed to be a pivotal determinant of the long-term prognosis in non-alcoholic fatty liver disease (NAFLD). Objective: We aimed to develop a novel nomogram-based non-invasive model to accurately predict significant fibrosis in patients with NAFLD. Methods: We designed a prospective cohort study including 207 patients with biopsy-proven NAFLD. Detailed anthropometric and fibrosis-related laboratory parameters were collected. A nomogram was established based on variables that were independently associated with significant fibrosis identified by the logistic regression model. Then it was compared with aspartate aminotransferase-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), FIB-4 and BARD score. Diagnostic accuracy was assessed according to area under the receiver operator characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values, and decision curve analysis. Results: Variables included in the nomogram were: waist-to-height ratio, hyaluronic acid, procollagen-III-peptide, chitinase-3-like protein 1, and cytokeratine-18 neoepitope M65. The discrimination ability of the nomogram (AUROC = 0.829, 95%CI 0.755-0.904) was significantly superior to APRI (AUROC = 0.670, 95%CI 0.563-0.777), NFS (AUROC = 0.601, 95%CI 0.480-0.722), FIB-4 (AUROC = 0.624, 95%CI 0.511-0.736) and BARD (AUROC = 0.579, 95%CI 0.459-0.699) for significant fibrosis (all p < 0.05). The nomogram showed a larger net benefit to aid in decision-making as to whether biopsy is required. Conclusions: This novel nomogram was more accurate, and achieved higher net benefit than APRI, NFS, FIB-4 and BARD to detect significant fibrosis. It can be useful as a non-invasive method to screen ≥F2 fibrosis in the overall population with NAFLD.


Subject(s)
Fibrosis/blood , Fibrosis/pathology , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/pathology , Adult , Anthropometry , Aspartate Aminotransferases/blood , Biomarkers/blood , Biopsy , Blood Platelets/cytology , Female , Fibrosis/diagnosis , Fibrosis/mortality , Humans , Liver Function Tests/methods , Male , Middle Aged , Nomograms , Non-alcoholic Fatty Liver Disease/complications , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity
8.
JACC Clin Electrophysiol ; 5(4): 480-489, 2019 04.
Article in English | MEDLINE | ID: mdl-31000102

ABSTRACT

OBJECTIVES: This study proposed entropy as a new late gadolinium enhanced cardiac magnetic resonance-derived parameter to evaluate tissue inhomogeneity, independent of signal intensity thresholds. This study hypothesized that entropy within the scar is associated with ventricular arrhythmias (VAs), whereas entropy of the entire left ventricular (LV) myocardium is associated with mortality. BACKGROUND: In patients after myocardial infarction, the heterogeneity of fibrosis determines the substrate for VA. Fibrosis in remote areas has been associated with heart failure and mortality. Late gadolinium-enhanced cardiac magnetic resonance has been used to delineate fibrosis, but available methods depend on signal intensity thresholds and results have been inconsistent. METHODS: Consecutive post-myocardial infarction patients undergoing late gadolinium enhanced cardiac magnetic resonance prior to implantable cardioverter-defibrillator implantation were included. From cardiac magnetic resonance imaging, total scar size, scar gray zone, scar transmurality, and tissue entropy were derived. Patients were followed for appropriate implantable cardioverter-defibrillator therapy and mortality. RESULTS: A total of 154 patients (age 64 ± 10 years, 84% male, LV ejection fraction 29 ± 10%, 47% acute revascularization) were included. During a median follow-up of 56 (interquartile range: 40 to 73) months, appropriate implantable cardioverter-defibrillator therapy occurred in 46 patients (30%), and 41 patients (27%) died. From multivariable analysis, higher entropy of the scar (hazard ratio [HR]: 1.9; 95% confidence interval [CI]: 1.0 to 3.5; p = 0.042) was independently associated with VA, after adjusting for multivessel disease, acute revascularization, LV ejection fraction, scar gray zone, and transmurality. Entropy of the entire LV was independently associated with mortality (HR: 3.2; 95% CI: 1.1 to 9.9; p = 0.038). CONCLUSIONS: High entropy within the scar was associated with VA and may indicate an arrhythmogenic scar. High entropy of the entire LV was associated with mortality and may reflect a fibrosis pattern associated with adverse remodeling.


Subject(s)
Arrhythmias, Cardiac , Fibrosis , Heart Ventricles , Magnetic Resonance Imaging/methods , Myocardial Infarction , Aged , Arrhythmias, Cardiac/diagnostic imaging , Arrhythmias, Cardiac/mortality , Arrhythmias, Cardiac/physiopathology , Cicatrix/diagnostic imaging , Cicatrix/physiopathology , Defibrillators, Implantable , Entropy , Female , Fibrosis/diagnostic imaging , Fibrosis/mortality , Fibrosis/physiopathology , Gadolinium/therapeutic use , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/physiopathology , Retrospective Studies
9.
J Am Coll Cardiol ; 72(21): 2577-2587, 2018 11 27.
Article in English | MEDLINE | ID: mdl-30466515

ABSTRACT

BACKGROUND: Myocardial fibrosis (MF) according to cardiac magnetic resonance (CMR) is a frequent finding in Chagas cardiomyopathy and has been associated with risk factors of poor outcome. OBJECTIVES: The goal of this study was to determine the prognostic value of MF in predicting combined hard events or all-cause mortality. METHODS: Patients with Chagas cardiomyopathy who had a previous CMR evaluation were included, and clinical follow-up was retrospectively obtained. The primary outcome was a combination of all-cause mortality, heart transplantation, antitachycardia pacing or appropriate shock from an implantable cardioverter-defibrillator, and aborted sudden cardiac death; the secondary outcome was all-cause mortality. RESULTS: A total of 130 patients were included; mean age was 53.6 ± 11.5 years, and 53.9% were female. The majority of patients reported no symptoms of heart failure or arrhythmia, but electrocardiographic and echocardiographic abnormalities were common. On CMR, left ventricular dilatation and dysfunction were frequent, and MF was found in 76.1%, with a mean mass of 15.2 ± 16.5 g. Over a median follow-up of 5.05 years, 58 (44.6%) patients reached the combined endpoint, and 45 (34.6%) patients died. MF was associated with the primary outcome as a continuous variable (adjusted hazard ratio: 1.031; 95% CI: 1.013 to 1.049; p = 0.001) and as a categorical variable (MF ≥12.3 g) (adjusted hazard ratio: 2.107; 95% CI: 1.111 to 3.994; p = 0.022), independently from the Rassi risk score. MF expressed as a continuous variable was also associated with all-cause mortality (adjusted hazard ratio: 1.028; 95% CI: 1.005 to 1.051; p = 0.017) independently from the Rassi risk score. CONCLUSIONS: MF is an independent predictor of adverse outcome in Chagas cardiomyopathy. Our data may support the use of CMR in better risk-stratifying this population and possibly guiding therapy.


Subject(s)
Chagas Cardiomyopathy/diagnostic imaging , Chagas Cardiomyopathy/mortality , Myocardium/pathology , Adult , Aged , Cohort Studies , Echocardiography/trends , Female , Fibrosis/diagnostic imaging , Fibrosis/mortality , Follow-Up Studies , Humans , Magnetic Resonance Imaging, Cine/trends , Male , Middle Aged , Prognosis , Retrospective Studies , Time Factors
10.
PLoS One ; 13(7): e0178997, 2018.
Article in English | MEDLINE | ID: mdl-30044781

ABSTRACT

BACKGROUND: Dementia is characterized by prolonged progressive disability. Therefore, predicting mortality is difficult. An accurate prediction tool may be useful to ensure that end-of-life patients with dementia receive timely palliative care. PURPOSE: This study aims to establish a survival prediction model for elderly patients with dementia in Taiwan. METHODS: Data from the 2001 to 2010 National Health Insurance Research Database in Taiwan were used to identify 37,289 patients with dementia aged ≥65 years for inclusion in this retrospective longitudinal study. Moreover, this study examined the mortality indicators for dementia among demographic characteristics, chronic physical comorbidities, and medical procedures. A Cox proportional hazards model with time-dependent covariates was used to estimate mortality risk, and risk score functions were formulated using a point system to establish a survival prediction model. The prediction model was then tested using the area under the receiver operating characteristic curve. RESULTS: Thirteen mortality risk factors were identified: age, sex, stroke, chronic renal failure, liver cirrhosis, cancer, pressure injury, and retrospectively retrieved factors occurring in the 6 months before death, including nasogastric tube placement, supplemental oxygen supply, ≥2 hospitalization, receiving ≥1 emergency services, ≥2 occurrences of cardiopulmonary resuscitation, and receiving ≥2 endotracheal intubations. The area under the receiver operating characteristic curves for this prediction model for mortality at 6 and 12 months were 0.726 and 0.733, respectively. CONCLUSIONS: The survival prediction model demonstrated moderate accuracy for predicting mortality at 6 and 12 months before death in elderly patients with dementia. This tool may be valuable for helping health care providers and family caregivers to make end-of-life care decisions.


Subject(s)
Dementia/mortality , Fibrosis/mortality , Geriatric Psychiatry , Kidney Failure, Chronic/mortality , Aged , Aged, 80 and over , Comorbidity , Dementia/complications , Dementia/physiopathology , Female , Fibrosis/physiopathology , Forecasting , Geriatrics/trends , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/physiopathology , Longitudinal Studies , Male , Mortality , Oxygen , Risk Factors , Terminal Care
11.
Saudi J Gastroenterol ; 24(4): 211-219, 2018.
Article in English | MEDLINE | ID: mdl-29956688

ABSTRACT

Background/Aim: Due to epidemic levels of obesity and type 2 diabetes mellitus (DM), nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) will be driving factors in liver disease burden in the coming years in Saudi Arabia and United Arab Emirates (UAE). Materials and Methods: Models were used to estimate NAFLD and NASH disease progression, primarily based on changes in adult prevalence rates of adult obesity and DM. The published estimates and expert interviews were used to build and validate the model projections. Results: In both countries, the prevalence of NAFLD increased through 2030 parallel to projected increases in the prevalence of obesity and DM. By 2030, there were an estimated 12,534,000 NAFLD cases in Saudi Arabia and 372,000 cases in UAE. Increases in NASH cases were relatively greater than the NAFLD cases due to aging of the population and disease progression. Likewise, prevalent cases of compensated cirrhosis and advanced liver disease are projected to at least double by 2030, while annual incident liver deaths increase in both countries to 4800 deaths in Saudi Arabia and 140 deaths in UAE. Conclusions: Continued high rates of adult obesity and DM, in combination with aging populations, suggest that advanced liver disease and mortality attributable to NAFLD/NASH will increase across both countries. Reducing the growth of the NAFLD population, along with potential therapeutic options, will be needed to reduce liver disease burden.


Subject(s)
Liver Diseases/epidemiology , Liver/pathology , Non-alcoholic Fatty Liver Disease/economics , Non-alcoholic Fatty Liver Disease/epidemiology , Adult , Cost of Illness , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Female , Fibrosis/epidemiology , Fibrosis/mortality , Humans , Liver Diseases/mortality , Male , Metabolic Syndrome/epidemiology , Middle Aged , Non-alcoholic Fatty Liver Disease/mortality , Obesity/epidemiology , Prevalence , Saudi Arabia/epidemiology , United Arab Emirates/epidemiology
13.
Neuroendocrinology ; 106(2): 139-147, 2018.
Article in English | MEDLINE | ID: mdl-28384635

ABSTRACT

BACKGROUND: Mesenteric fibrosis (MF) surrounding a lymph node metastasis is a known phenomenon in midgut neuroendocrine tumors (NETs) with characteristic radiological appearance. Its etiology is poorly understood as it affects some but not all midgut NET patients with lymphatic involvement. This study assessed a potential relationship of MF with carcinoid syndrome, urinary 5-hydroxyindoleacetic acid (5-HIAA), and carcinoid heart disease (CHD). METHODS: A cohort of 81 patients with pathologically proven NETs with the primary site in the midgut and mesenteric lymphatic metastases on imaging were retrospectively included. Imaging characteristics of lymphatic and hepatic metastases at diagnosis (size, number, burden, and morphologic features, including presence of MF), Ki67 grading, 5-HIAA, functionality, and development of CHD were analyzed. RESULTS: Overall, 54% of patients had MF. The presence of MF was more frequently associated with mesenteric vessel encasement (100 vs. 46% without MF; p < 0.001), presence of hepatic metastases (91 vs. 62%; p = 0.002), larger hepatic tumor burden (15 vs. 5%; p = 0.001), and functionality (86 vs. 43%; p < 0.001). Multivariate analysis revealed 5-HIAA ≥395 µmol/day (p = 0.020), age (p = 0.013), and largest lymphatic metastasis ≥24 mm (p = 0.009) as independent predictors of MF, while functionality (p = 0.098) and CHD (p = 0.070) showed a tendency towards significance. MF was associated with decreased time to development of CHD in functional midgut NETs (p = 0.043). CONCLUSIONS: We found a significant association of MF with metastatic patterns and with criteria of functionality. The association of MF with elevated 5-HIAA, and consecutively with carcinoid syndrome and potential development of CHD, suggests a linked pathophysiological mechanism, which might be similar to that of endocardial fibrosis.


Subject(s)
Gastrointestinal Neoplasms/diagnostic imaging , Lymphatic Metastasis/diagnostic imaging , Neuroendocrine Tumors/diagnostic imaging , Aged , Cohort Studies , Female , Fibrosis/diagnostic imaging , Fibrosis/mortality , Fibrosis/pathology , Fibrosis/surgery , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/surgery , Humans , Hydroxyindoleacetic Acid/urine , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Grading , Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/surgery , Retrospective Studies , Tumor Burden
14.
PLoS One ; 12(10): e0185997, 2017.
Article in English | MEDLINE | ID: mdl-29020046

ABSTRACT

BACKGROUND & AIMS: Prognostic tests are critical in the management of patients with cirrhosis and ascites. Biological tests or scores perform poorly in that situation. Mid-infrared fibre evanescent wave spectroscopy (MIR-FEWS) which allows for global serum metabolic profiling may provide more relevant information by measuring a wider range of metabolic parameters in serum. Here we present the accuracy of a MIR-FEWS based predictive model for the prognosis of 6 months survival in patients with ascites and cirrhosis. METHODS: Patients with ascites were prospectively included and followed up for 6 months. MIR-FEWS spectra were measured in serum samples. The most informative spectral variables obtained by MIR-FEWS were selected by FADA algorithm and then used to build the MIR model. Accuracy of this model was assessed by ROC curves and 90%/10% Monte Carlo cross-validation. MIR model accuracy for 6 months survival was compared to that of the Child-Pugh and MELD scores. RESULTS: 119 patients were included. The mean age was 57.36±13.70, the MELD score was 16.32±6.26, and the Child-Pugh score was 9.5±1.83. During follow-up, 23 patients died (20%). The MIR model had an AUROC for 6 months mortality of 0.90 (CI95: 0.88-0.91), the MELD 0.77 (CI95: 0.66-0.89) and Child-Pugh 0.76 (CI95: 0.66-0.88). MELD and Child-Pugh AUROCs were significantly lower than that of the MIR model (p = 0.02 and p = 0.02 respectively). Multivariate logistic regression analysis showed that MELD (p<0.05, OR:0.86;CI95:0.76-0.97), Beta blockers (p = 0.036;OR:0.20;CI95:0.04-0.90), and the MIR model (p<0.001; OR:0.50; CI95:0.37-0.66), were significantly associated with 6 months mortality. CONCLUSIONS: In this pilot study MIR-FEWS more accurately assess the 6-month prognosis of patients with ascites and cirrhosis than the MELD or Child-Pugh scores. These promising results, if confirmed by a larger study, suggest that mid infrared spectroscopy could be helpful in the management of these patients.


Subject(s)
Ascites/blood , Ascites/diagnosis , Fibrosis/blood , Fibrosis/diagnosis , Serum/metabolism , Spectrophotometry, Infrared/methods , Algorithms , Area Under Curve , Ascites/mortality , Biomarkers/blood , Female , Fibrosis/mortality , Humans , Male , Middle Aged , Prognosis , ROC Curve , Reproducibility of Results , Risk Assessment , Sensitivity and Specificity
15.
Eur Heart J ; 38(46): 3423-3430, 2017 Dec 07.
Article in English | MEDLINE | ID: mdl-29020384

ABSTRACT

BACKGROUND: Fibrosis is a key pathological process in many chronic inflammatory disease states. AIMS: We hypothesized that tissue inhibitor metalloproteinase-1 and matrix metalloproteinase-9 (TIMP-1 and MMP-9), biomarkers of fibrosis, would predict all-cause mortality and we assessed the incremental value of these biomarkers when adjusting for clinical and other biomarkers. METHODS: The cohort included 5511 community-dwelling participants in the AGES-Reykjavik Study. The baseline Cox proportional hazards regression model was based on the Framingham Risk Score variables; we added TIMP-1, MMP-9, serum high-sensitivity C-reactive protein (hsCRP), and estimated glomerular filtration rate (eGFR). The primary outcome was all-cause 10-year mortality. Cause of death was categorized as cardiovascular death (CVD), cancer death, and other causes. RESULTS: Participants averaged 76 years and 43% were male. Ten-year mortality was 41% (2263 deaths). Of these, 915 (16.6%) died of cardiovascular disease (CVD), 543 (9.9%) with cancer, and 805 (14.6%) from other causes. For 10-year mortality, age was the strongest predictor (log likelihood χ2 = 798.7, P < 0.0001), followed by TIMP-1 (χ2 = 125.2, P < 0.0001), female gender, current smoker, diabetes mellitus, total cholesterol, eGFR (χ2 16.7, P < 0.0001), body mass index, and hsCRP (χ2 11.3, P = 0.0008) in that order. TIMP-1 and hsCRP had the highest continuous net reclassification improvement over the baseline model for 5-year survival [net reclassification index (NRI) 0.28 and 0.19, respectively, both P < 0.0001] and for 10-year survival (NRI 0.19 and 0.11, respectively, both statistically significant). CONCLUSION: TIMP-1 is the strongest predictor of all-cause mortality after age. The metabolic pathways regulating extracellular matrix homeostasis and fibrogenic processes appear pathologically relevant and are prognostically important.


Subject(s)
Cardiovascular Diseases/pathology , Tissue Inhibitor of Metalloproteinase-1/metabolism , Aged , Aged, 80 and over , Biomarkers/metabolism , Cardiovascular Diseases/mortality , Cause of Death , Female , Fibrosis/mortality , Humans , Iceland/epidemiology , Male , Matrix Metalloproteinase 9/metabolism , Neoplasms/mortality , Risk Assessment/methods
16.
Radiology ; 285(3): 999-1010, 2017 12.
Article in English | MEDLINE | ID: mdl-28682164

ABSTRACT

Purpose To assess the effects of preexisting nonmalignant portal vein thrombosis (PVT) on mortality, clinical relapse, shunt dysfunction, and overt hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) placement. Materials and Methods This retrospective study was approved by the institutional ethics committee, and written informed consent was obtained from all patients. From March 2001 to December 2014, 1171 consecutive patients with cirrhosis (762 men, 409 women; mean age, 50.0 years ± 12.8) and PVT (n = 212; 18%) or without PVT (n = 959; 82%) who underwent TIPS placement were included. The association between PVT and outcomes after TIPS placement was measured by using Fine and Gray competing risk regression model after adjusting for important baseline characteristics or by using propensity score. The Wald test was used to assess the homogeneity of the effects of PVT across different strata (stratified PVT according to the stages, degrees, and extents) and major subgroups. Results During a median follow-up period of 28.4 months, 507 (43%) patients died, 373 (32%) experienced clinical relapse, 217 (19%) developed shunt dysfunction, and 475 (41%) experienced overt HE. Compared with patients without PVT, patients with PVT had a similar risk of mortality (adjusted hazard ratio, 0.82; 95% confidence interval [CI]: 0.63, 1.09; P = .17), clinical relapse (adjusted hazard ratio, 1.24; 95% CI: 0.92, 1.69; P = .15), shunt dysfunction (adjusted hazard ratio, 1.03; 95% CI: 0.70, 1.51; P = .43), and overt HE (adjusted hazard ratio, 0.88; 95% CI: 0.70, 1.11; P = .29). Furthermore, the effects of PVT were consistent across the relevant strata and subgroups. Conclusion There was no evidence that preexisting PVT was associated with an improved or worsened outcome after TIPS. © RSNA, 2017 Online supplemental material is available for this article.


Subject(s)
Fibrosis/mortality , Fibrosis/surgery , Hypertension, Portal/mortality , Hypertension, Portal/surgery , Portal Vein/surgery , Portasystemic Shunt, Transjugular Intrahepatic/mortality , Venous Thrombosis/mortality , Causality , China/epidemiology , Comorbidity , Female , Fibrosis/diagnostic imaging , Humans , Hypertension, Portal/diagnostic imaging , Male , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/statistics & numerical data , Prevalence , Retrospective Studies , Risk Factors , Survival Rate , Treatment Outcome , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/surgery
17.
Clin Gastroenterol Hepatol ; 15(10): 1521-1530.e8, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28479502

ABSTRACT

BACKGROUND & AIMS: Statins have been variably shown to decrease risk and complications of chronic liver diseases (CLDs). We performed a systematic review and meta-analysis to evaluate the association between statins and risk of cirrhosis and related complications in patients with CLDs. METHODS: Through a systematic literature search up to March 2017, we identified 13 studies (3 randomized trials, 10 cohort studies) in adults with CLDs, reporting the association between statin use and risk of development of cirrhosis, decompensated cirrhosis, improvements in portal hypertension, or mortality. Pooled relative risk (RR) estimates with 95% confidence interval (CIs) were calculated using random effects model. Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess quality of evidence. RESULTS: Among 121,058 patients with CLDs (84.5% with hepatitis C), 46% were exposed to statins. In patients with cirrhosis, statin use was associated with 46% lower risk of hepatic decompensation (4 studies; RR, 0.54; 95% CI, 0.46-0.62; I2 = 0%; moderate-quality evidence), and 46% lower mortality (5 studies; RR, 0.54; 95% CI, 0.47-0.61; I2 = 10%; moderate-quality evidence). In patients with CLD without cirrhosis, statin use was associated with a nonsignificant (58% lower) risk of development of cirrhosis or fibrosis progression (5 studies; RR, 0.42; 95% CI, 0.16-1.11; I2 = 99%; very-low-quality evidence). In 3 randomized controlled trials, statin use was associated with 27% lower risk of variceal bleeding or progression of portal hypertension (hazard ratio, 0.73; 95% CI, 0.59-0.91; I2 = 0%; moderate-quality evidence). CONCLUSIONS: Based on a systematic review and meta-analysis, statin use is probably associated with lower risk of hepatic decompensation and mortality, and might reduce portal hypertension, in patients with CLDs. Prospective observational studies and randomized controlled trials are needed to confirm this observation.


Subject(s)
Alcoholism/complications , Fibrosis/epidemiology , Fibrosis/prevention & control , Hepatitis B, Chronic/complications , Hepatitis C, Chronic/complications , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Fibrosis/mortality , Humans , Liver Failure/epidemiology , Liver Failure/mortality , Liver Failure/prevention & control , Risk Assessment , Survival Analysis
18.
Arthritis Care Res (Hoboken) ; 69(11): 1764-1770, 2017 11.
Article in English | MEDLINE | ID: mdl-28544788

ABSTRACT

OBJECTIVE: To determine if a unique subtype of scleroderma muscle disease exists by comparing the clinical features of systemic sclerosis (SSc; scleroderma) patients with predominant fibrosis on muscle biopsy to those with inflammatory muscle histopathology. METHODS: This retrospective, cross-sectional study included SSc patients with muscle weakness and an available muscle biopsy. Biopsies with fibrosis but without inflammation/necrosis were designated as "fibrosing myopathy," and those with inflammation and/or necrosis were assigned a category of "inflammatory myopathy." Clinical data, including features of SSc, serum creatine kinase (CK) levels, electromyography, autoantibody profile, and survival, were compared between the 2 groups. RESULTS: The study population consisted of 37 weak SSc patients, 8 with fibrosing myopathy and 29 with inflammatory myopathy. Compared to those with inflammatory myopathy, patients with fibrosing myopathy were more likely to have diffuse SSc skin subtype (87% versus 62%; P = 0.18), African American race (62.5% versus 37.9%; P = 0.20), and a lower mean ± SD forced vital capacity (55.5 ± 31.9 versus 66.4 ± 17.6; P = 0.23). They also had lower mean ± SD CK values (516 ± 391 versus 2,477 ± 3,511 IU/liter; P = 0.007) and lower aldolase values (13.8 ± 4.7 versus 27.3 ± 4.7; P = 0.01). Patients with fibrosing myopathy had a significantly higher mortality (5 of 8 [62.5%] versus 4 of 29 [14.3%]; P = 0.005). CONCLUSION: Fibrosing myopathy is a unique histologic subtype of muscle disease among weak patients with SSc and is associated with significantly worse mortality compared to those with inflammation and/or necrosis on muscle biopsy.


Subject(s)
Muscle, Skeletal/pathology , Muscular Diseases/diagnosis , Muscular Diseases/mortality , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/mortality , Adult , Cohort Studies , Cross-Sectional Studies , Female , Fibrosis/diagnosis , Fibrosis/mortality , Humans , Male , Middle Aged , Mortality/trends , Retrospective Studies
19.
Clin Rev Allergy Immunol ; 52(3): 424-435, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27515672

ABSTRACT

There is a paucity of information related to the usefulness of corticosteroid therapy in autoimmune hepatitis (AIH) with decompensated cirrhosis. In this study, we sought to determine the therapeutic effect of corticosteroids in this special group of AIH patients. Eighty-two AIH patients with decompensated cirrhosis were included through a retrospective analysis from January 2009 to September 2015. Sixty-four patients were treated with corticosteroids while 18 patients did not receive any corticosteroids. Clinical, laboratory, and histological characteristics and outcomes were analyzed comparing corticosteroid-treated and untreated groups. Patients that did not receive corticosteroids were older than corticosteroid-treated patients and had a worse survival. In corticosteroid-treated group, 40 of 64 patients reverted to compensated state and 15 patients remained decompensated, while 9 patients experienced liver-related death or transplantation. Patients who reverted to compensated state had significantly greater ALT, AST, GGT, white blood cell count, and platelet levels at presentation. Changes (Δ) in total bilirubin (TBIL) and MELD scores at day 7 after starting corticosteroid therapy revealed favorable predictive effects of treatment outcomes. Survival was significantly greater in patients with a ΔTBIL <-0.196 mg/dL (p = 0.001) 7 days after treatment. Infection was the most common cause of death or transplantation in the patients with treatment failure. Although it cannot be determined whether the results were due to the therapy or underlying patient characteristics, survival was greater in the corticosteroid-treated group with the benefit being greatest in patients with the greatest decrease in TBIL at day 7 after starting corticosteroid therapy.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Bilirubin/blood , Fibrosis/drug therapy , Hepatitis, Autoimmune/drug therapy , Liver Failure/drug therapy , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Aspartate Aminotransferases/blood , Disease Progression , Female , Fibrosis/mortality , Hepatitis, Autoimmune/mortality , Humans , Liver Failure/mortality , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome , Young Adult
20.
BMC Gastroenterol ; 16(1): 135, 2016 Oct 28.
Article in English | MEDLINE | ID: mdl-27793116

ABSTRACT

BACKGROUND: Toxic liver diseases are mainly caused by drug-induced liver injury (DILI). We assessed incidences and outcomes of DILI including associated factors for mortality. METHODS: We performed a population-based study of hospitalized patients with DILI. Information was retrieved from the Nationwide Hospital Admission Data using ICD-10 code of toxic liver diseases (K71) and additional codes (T36-T65). The associated factors were analyzed with log-rank test, univariate and multiple cox regression analysis. RESULTS: During 2009-2013, a total of 159,061 (average 21,165 per year) admissions were related to liver diseases. 6,516 admissions (1,303 per year) were due to toxic liver diseases. The most common type of toxic liver disease was acute hepatitis (33.5 %). In-hospital and 90-day mortality rates were 3.4 % and 17.2 %. DILI with cirrhosis yielded the highest in-hospital and 90-day mortality rates (15.8 % and 47.4 %). Acetaminophen, cirrhosis and age ≥ 60 years were seen in 0.5 %, 8.3 % and 50.1 % of patients who died versus 5 %, 2.3 % and 32.4 % of survivors. Factors associated with mortality were cirrhosis (HR 2.72, 95 % CI: 2.33-3.19), age ≥60 years (HR 2.16, 95 % CI: 1.96-2.38), human immunodeficiency viral infection (HR 2.11, 95 % CI: 1.88-2.36), chronic kidney disease (HR 1.59, 95 % CI: 1.33-1.90), chronic obstructive pulmonary disease and bronchiectasis (HR 1.55, 95 % CI: 1.17-2.04), malnutrition (HR 1.43, 95 % CI: 1.10-1.86) and male (HR 1.31, 95 % CI: 1.21-1.43). Acetaminophen DILI yielded lower risks of mortality (HR 0.24, 95 % CI: 0.13-0.42). The most common causes of DILI were acetaminophen (35.0 %) and anti-tuberculous drugs (34.7 %). CONCLUSIONS: DILI is an uncommon indication for hospitalization carrying lower risks of death except in patients with non-acetaminophen, cirrhosis, elderly or concomitant diseases.


Subject(s)
Chemical and Drug Induced Liver Injury/mortality , Hospital Mortality , Hospitalization/statistics & numerical data , Acetaminophen/adverse effects , Adult , Age Factors , Aged , Analgesics, Non-Narcotic/adverse effects , Antitubercular Agents/adverse effects , Chemical and Drug Induced Liver Injury/complications , Chemical and Drug Induced Liver Injury/economics , Chemical and Drug Induced Liver Injury/epidemiology , Databases, Factual , Female , Fibrosis/chemically induced , Fibrosis/mortality , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sex Factors , Thailand/epidemiology
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