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1.
J Am Coll Cardiol ; 72(21): 2577-2587, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30466515

RESUMO

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.


Assuntos
Cardiomiopatia Chagásica/diagnóstico por imagem , Cardiomiopatia Chagásica/mortalidade , Miocárdio/patologia , Adulto , Idoso , Estudos de Coortes , Ecocardiografia/tendências , Feminino , Fibrose/diagnóstico por imagem , Fibrose/mortalidade , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
2.
PLoS One ; 13(7): e0178997, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30044781

RESUMO

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.


Assuntos
Demência/mortalidade , Fibrose/mortalidade , Psiquiatria Geriátrica , Falência Renal Crônica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Demência/complicações , Demência/fisiopatologia , Feminino , Fibrose/fisiopatologia , Previsões , Geriatria/tendências , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Estudos Longitudinais , Masculino , Mortalidade , Oxigênio , Fatores de Risco , Assistência Terminal
3.
Saudi J Gastroenterol ; 24(4): 211-219, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29956688

RESUMO

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.


Assuntos
Hepatopatias/epidemiologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/economia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2/epidemiologia , Progressão da Doença , Feminino , Fibrose/epidemiologia , Fibrose/mortalidade , Humanos , Hepatopatias/mortalidade , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Obesidade/epidemiologia , Prevalência , Arábia Saudita/epidemiologia , Emirados Árabes Unidos/epidemiologia
5.
Neuroendocrinology ; 106(2): 139-147, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28384635

RESUMO

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.


Assuntos
Neoplasias Gastrointestinais/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Idoso , Estudos de Coortes , Feminino , Fibrose/diagnóstico por imagem , Fibrose/mortalidade , Fibrose/patologia , Fibrose/cirurgia , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Ácido Hidroxi-Indolacético/urina , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Estudos Retrospectivos , Carga Tumoral
6.
PLoS One ; 12(10): e0185997, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29020046

RESUMO

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.


Assuntos
Ascite/sangue , Ascite/diagnóstico , Fibrose/sangue , Fibrose/diagnóstico , Soro/metabolismo , Espectrofotometria Infravermelho/métodos , Algoritmos , Área Sob a Curva , Ascite/mortalidade , Biomarcadores/sangue , Feminino , Fibrose/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade
7.
Eur Heart J ; 38(46): 3423-3430, 2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29020384

RESUMO

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.


Assuntos
Doenças Cardiovasculares/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Fibrose/mortalidade , Humanos , Islândia/epidemiologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias/mortalidade , Medição de Risco/métodos
8.
Radiology ; 285(3): 999-1010, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28682164

RESUMO

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.


Assuntos
Fibrose/mortalidade , Fibrose/cirurgia , Hipertensão Portal/mortalidade , Hipertensão Portal/cirurgia , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/mortalidade , Trombose Venosa/mortalidade , Causalidade , China/epidemiologia , Comorbidade , Feminino , Fibrose/diagnóstico por imagem , Humanos , Hipertensão Portal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática/estatística & dados numéricos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/cirurgia
9.
Clin Gastroenterol Hepatol ; 15(10): 1521-1530.e8, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28479502

RESUMO

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.


Assuntos
Alcoolismo/complicações , Fibrose/epidemiologia , Fibrose/prevenção & controle , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fibrose/mortalidade , Humanos , Falência Hepática/epidemiologia , Falência Hepática/mortalidade , Falência Hepática/prevenção & controle , Medição de Risco , Análise de Sobrevida
10.
Arthritis Care Res (Hoboken) ; 69(11): 1764-1770, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28544788

RESUMO

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.


Assuntos
Músculo Esquelético/patologia , Doenças Musculares/diagnóstico , Doenças Musculares/mortalidade , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/mortalidade , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Fibrose/diagnóstico , Fibrose/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Retrospectivos
11.
Clin Rev Allergy Immunol ; 52(3): 424-435, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27515672

RESUMO

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.


Assuntos
Corticosteroides/uso terapêutico , Bilirrubina/sangue , Fibrose/tratamento farmacológico , Hepatite Autoimune/tratamento farmacológico , Falência Hepática/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Progressão da Doença , Feminino , Fibrose/mortalidade , Hepatite Autoimune/mortalidade , Humanos , Falência Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
BMC Gastroenterol ; 16(1): 135, 2016 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-27793116

RESUMO

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.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Acetaminofen/efeitos adversos , Adulto , Fatores Etários , Idoso , Analgésicos não Entorpecentes/efeitos adversos , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/economia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Bases de Dados Factuais , Feminino , Fibrose/induzido quimicamente , Fibrose/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Tailândia/epidemiologia
14.
Am J Transplant ; 16(7): 1982-98, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26990570

RESUMO

Interstitial fibrosis and tubular atrophy (IFTA) is found in approximately 25% of 1-year biopsies posttransplant. It is known that IFTA correlates with decreased graft survival when histological evidence of inflammation is present. Identifying the mechanistic etiology of IFTA is important to understanding why long-term graft survival has not changed as expected despite improved immunosuppression and dramatically reduced rates of clinical acute rejection (AR) (Services UDoHaH. http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expression profiles of 234 graft biopsy samples were obtained with matching clinical and outcome data. Eighty-one IFTA biopsies were divided into subphenotypes by degree of histological inflammation: IFTA with AR, IFTA with inflammation, and IFTA without inflammation. Samples with AR (n = 54) and normally functioning transplants (TX; n = 99) were used in comparisons. A novel analysis using gene coexpression networks revealed that all IFTA phenotypes were strongly enriched for dysregulated gene pathways and these were shared with the biopsy profiles of AR, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. These molecular biopsy profiles correlated with future graft loss in IFTA samples without inflammation.


Assuntos
Atrofia/mortalidade , Fibrose/mortalidade , Perfilação da Expressão Gênica , Rejeição de Enxerto/mortalidade , Transplante de Rim/métodos , Túbulos Renais/patologia , Nefrite Intersticial/mortalidade , Atrofia/genética , Fibrose/genética , Taxa de Filtração Glomerular , Rejeição de Enxerto/genética , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/cirurgia , Testes de Função Renal , Túbulos Renais/metabolismo , Nefrite Intersticial/genética , Prognóstico , Fatores de Risco , Taxa de Sobrevida
15.
Am J Transplant ; 16(8): 2445-52, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26998739

RESUMO

Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV-positive, compared to 443 HCV-negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1-, 3-, and 5-year survival were similar in HCV RNA-positive versus -negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long-term follow-up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon-free HCV therapies this should not be a barrier to LuTx.


Assuntos
Fibrose/mortalidade , Rejeição de Enxerto/mortalidade , Hepatite C/cirurgia , Cirrose Hepática/mortalidade , Transplante de Pulmão/mortalidade , Complicações Pós-Operatórias/mortalidade , Adulto , Feminino , Fibrose/etiologia , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Humanos , Cirrose Hepática/etiologia , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco
16.
J Nutr Health Aging ; 20(4): 408-14, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26999241

RESUMO

OBJECTIVES: To identify main prognostic factors for 5-year mortality among age-related comorbidities (ARCs) in older people living with HIV (PLHIV). DESIGN: A prospective, multicentre cohort study with a 5-year follow-up period in the late HAART era (from January 2008 to December 2012). SETTING: The Dat'AIDS cohort involving 12 French hospitals. PARTICIPANTS: All actively followed HIV-1 infected patients aged 60 or older. MEASUREMENTS: The study endpoint was all-cause five-year mortality. The following ARCs were considered: chronic renal disease, cardiovascular diseases, cancer, chronic pulmonary disease, cirrhosis, diabetes and nutritional status. Hepatitis C (HCV), hepatitis B (HBV) co-infection and sociodemographic characteristics were also evaluated. Cox's Proportional Hazards model was used for multivariate analysis. RESULTS: Among 1415 PLHIV aged 60 or more patients included, mean age was 66±5.5 years; 154 died (mortality rate 2.47/100 patient-years). The most prevalent ARCs were chronic renal disease (20.1%), diabetes (14.2%) and cardiovascular diseases (12.2%). By multivariate analysis, chronic renal disease (adjusted hazard ratio (aHR)=2.25; 95% confidence interval (CI) [1.58-2.21]; p<10-4), cardiovascular diseases (aHR=2.40; 95%CI[1.64-3.52]; p<10-4), non-HIV related cancer (aHR=1.91; 95%CI[1.20-3.05]; p=0.007), cirrhosis (aHR=2.99; 95%CI[1.68-5.33]; p<10-3), HCV co-infection (aHR=2.00; 95%CI[1.18-3.38]; p=0.009), low body mass index (aHR=2.42; 95%CI[1.46-4.01]; p<10-3) and CD4 cell count < 200 cells/µl (aHR=2.23; 95%CI[1.36-3.65]; p=0.002) were independently associated with 5 year mortality. CONCLUSION: Due to a high prevalence, chronic renal disease and cardiovascular disease are main prognostic factors for 5-year mortality among aged PLHIV.


Assuntos
Envelhecimento , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Insuficiência Renal Crônica/epidemiologia , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Estudos de Coortes , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/mortalidade , Feminino , Fibrose/epidemiologia , Fibrose/mortalidade , França/epidemiologia , Infecções por HIV/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal Crônica/mortalidade
17.
Am J Med Sci ; 351(2): 169-76, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26897272

RESUMO

BACKGROUND: Patients with cirrhosis and portal hypertensive complications have reduced survival. As such, it has been suggested that nonselective beta-blocker therapy in patients with advanced ascites is harmful. The aim of this study was, therefore, to determine the risk of mortality in patients with cirrhosis and ascites taking nonselective beta-blocker therapy for the prevention of variceal hemorrhage. MATERIALS AND METHODS: This study was a retrospective analysis of 2,419 patients with cirrhosis and portal hypertension admitted to Parkland Memorial Hospital (a university-affiliated county teaching hospital) from 2003-2010. Patients were subdivided into those with varices only, ascites only and those with both varices and ascites. The primary outcome measure for this study was all-cause in-hospital mortality. RESULTS: Overall, 68 of 1,039 (6.5%) patients taking beta-blockers died during their hospitalization, while 223 of 1,380 (16.2%) patients not taking beta-blockers died (P < 0.001). Beta-blocker use was also assessed in specific cohorts; mortality was 21.1% in patients with severe ascites with varices who were not taking beta-blockers compared with 8.9% in patients who were taking beta-blockers (P = 0.05). Overall, fewer patients taking beta-blockers died compared with those not taking beta-blockers in patients with varices only (6.4% versus 12.1%) and those with ascites with or without varices (6.6% versus 18.1%) (P < 0.001). CONCLUSIONS: Mortality was lower in patients with cirrhosis and portal hypertension taking nonselective beta-blockers than in those not taking beta-blockers. The use of nonselective beta-blockers provided a significant survival benefit in patients with all grades of ascites, including those with severe ascites.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Ascite/mortalidade , Fibrose/mortalidade , Mortalidade Hospitalar , Hipertensão Portal/mortalidade , Adulto , Idoso , Ascite/tratamento farmacológico , Feminino , Fibrose/tratamento farmacológico , Humanos , Hipertensão Portal/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Texas/epidemiologia , Varizes/tratamento farmacológico , Varizes/mortalidade
18.
Stat Methods Med Res ; 25(5): 2088-2102, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-24395866

RESUMO

Assessments of the discriminative performance of prognostic models have led to the development of several measures that extend the concept of discrimination as evaluated by the receiver operating characteristics curve and the area under the receiver operating characteristic curve (AUC) of diagnostic settings. Thus, several time-dependent-receiver operating characteristic curve and AUC(t) have been proposed. One of the most used, the cumulative/dynamic AUCC,D(t) is the probability that, given two randomly chosen patients, one having failed before t and the other having failed after t, the prognostic marker will be correctly ranked. In this paper, we propose a weighted AUCC,D(t) with time- and data-dependent weights as a summary measure of the mean AUCC,D(t), restricted to a finite time range to ensure its clinical relevance. A simulation study shows that estimated restricted mean AUC increased with the strength of association of the covariate with the outcome, with low impact of censoring, and adequate coverage of bootstrap confidence intervals. We illustrate this methodology to two real datasets from two randomized clinical trials to assess the prognostic factors of the overall mortality in patients who have compensated cirrhosis and to assess the prognostic factors of event-free survival in patients who have acute myeloid leukemia.


Assuntos
Intervalo Livre de Doença , Curva ROC , Área Sob a Curva , Fibrose/diagnóstico , Fibrose/mortalidade , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Probabilidade , Prognóstico , Fatores de Tempo
19.
PLoS One ; 10(5): e0126707, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25966025

RESUMO

BACKGROUND: Cardiac involvement in systemic sclerosis (SSc) is associated with a variable phenotype including heart failure, arrhythmias and pulmonary hypertension. The aim of the present study was to evaluate clinical characteristics, histopathological findings and outcome of patients with SSc and a clinical phenotype suggesting cardiac involvement. METHODS AND RESULTS: 25 patients with SSc and clinical signs of cardiac involvement were included between June 2007 and December 2010. They underwent routine clinical work-up including laboratory testing, echocardiography, left and right heart catheterization, holter recordings and endomyocardial biopsy. Primary endpoint (EP) was defined as the combination of cardiovascular death, arrhythmic endpoints (defined as appropriate discharge of implantable cardioverter defibrillator (ICD)) or rehospitalization due to heart failure. The majority of patients presented with slightly impaired left ventricular function (mean LVEF 54.1±9.0%, determined by echocardiography). Endomyocardial biopsies detected cardiac fibrosis in all patients with a variable area percentage of 8% to 32%. Cardiac inflammation was diagnosed as follows: No inflammation in 3.8%, isolated inflammatory cells in 38.5%, a few foci of inflammation in 30.8%, several foci of inflammation in 15.4%, and pronounced inflammation in 7.7% of patients. During follow up (FU) (22.5 months), seven (28%) patients reached the primary EP. Patients with subsequent events showed a higher degree of fibrosis and inflammation in the myocardium by trend. While patients with an inflammation grade 0 or 1 showed an event rate of 18.2%, the subgroup of patients with an inflammation grade 2 presented with an event rate of 25% versus an event rate of 50% in the subgroup of patients with an inflammation grade 3 and 4, respectively (p=0.193). Furthermore, the subgroup of patients with fibrosis grade 1 showed an event rate of 11%, patients with fibrosis grade 2 and 3 presented with an event rate of 33% and 42% respectively (p = 0.160). CONCLUSIONS: Patients with SSc and clinical signs of cardiac involvement presented with mildly impaired LVEF. Prognosis was poor with an event rate of 28% within 22.5 months FU and was associated with the degree of cardiac inflammation and fibrosis.


Assuntos
Fibrose/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Inflamação/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Adulto , Biópsia , Morte , Desfibriladores Implantáveis , Ecocardiografia , Feminino , Fibrose/mortalidade , Coração/fisiopatologia , Insuficiência Cardíaca/mortalidade , Humanos , Inflamação/mortalidade , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Escleroderma Sistêmico/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia
20.
Circ J ; 79(8): 1733-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26016925

RESUMO

BACKGROUND: The natural history of hypertrophic cardiomyopathy (HCM) varies from an asymptomatic benign course to a poor prognosis. Myocardial fibrosis may play a critical role in ventricular tachyarrhythmias (VT/VF); however, the clinical significance of tissue fibrosis by right ventricular (RV) biopsy in the long-term prognosis of HCM patients remains unclear. METHODS AND RESULTS: We enrolled 185 HCM patients (mean age, 57±14 years). The amount of fibrosis (%area) was quantified using a digital microscope. Hemodynamic, echocardiographic, and electrophysiologic parameters were also evaluated. Patients with severe fibrosis had longer QRS duration and positive late potential (LP) on signal-averaged ECG, resulting in a higher incidence of VT/VF. At the 5±4 year follow-up, VT/VF occurred in 31 (17%) patients. Multivariate Cox regression analysis revealed that tissue fibrosis (hazard ratio (HR): 1.65; P=0.003 per 10% increase), lower left ventricular ejection fraction (HR: 0.64; P=0.001 per 10% increase), and positive SAECG (HR: 3.14; P=0.04) led to a greater risk of VT/VF. The combination of tissue fibrosis severity and lower left ventricular ejection fraction could be used to stratify the risk of lethal arrhythmic events in HCM patients. CONCLUSIONS: Myocardial fibrosis in RV biopsy samples may contribute to abnormal conduction delay and spontaneous VT/VF, leading to a poor prognosis in HCM patients.


Assuntos
Arritmias Cardíacas , Cardiomegalia , Miocárdio/patologia , Volume Sistólico , Sístole , Adulto , Idoso , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Cardiomegalia/mortalidade , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Intervalo Livre de Doença , Feminino , Fibrose/mortalidade , Fibrose/patologia , Fibrose/fisiopatologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
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