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BACKGROUND: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD). AIM: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD. METHODS: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD. RESULTS: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074). CONCLUSIONS: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD.
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BACKGROUND & AIMS: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B-related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD)-related fibrosis diagnosis and establish a machine-learning (ML) model to improve the diagnostic performance. METHODS: A total of 946 biopsy-proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). RESULTS: The AUROCs of aMAP versus fibrosis-4 index (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut-off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB-4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM-plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM-plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM-plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). CONCLUSIONS: The aMAP score is capable of diagnosing MASLD-related fibrosis. The LSM-plus model could accurately identify MASLD-related cirrhosis and advanced fibrosis.
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Técnicas de Imagem por Elasticidade , Fígado , Humanos , Fígado/patologia , Biópsia , Biomarcadores , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Fibrose , Aspartato Aminotransferases , Curva ROCRESUMO
Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16â¯603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10â¯920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.
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Carcinoma Hepatocelular , Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Fígado Gorduroso , Neoplasias Hepáticas , Adulto , Humanos , Masculino , Adolescente , Pessoa de Meia-Idade , Feminino , Técnicas de Imagem por Elasticidade/métodos , Estudos de Coortes , Vibração , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/patologia , Hemorragia Gastrointestinal , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Neoplasias Hepáticas/patologiaRESUMO
BACKGROUND & AIMS: The changes in liver stiffness measurement (LSM) are unreliable to estimate regression of fibrosis during antiviral treatment for chronic hepatitis B (CHB) patients. The age-male-albumin-bilirubin-platelets score (aMAP), as an accurate hepatocellular carcinoma risk score, may reflect the liver fibrosis stage. Here, we aimed to evaluate the performance of aMAP for diagnosing liver fibrosis in CHB patients with or without treatment. METHODS: A total of 2053 patients from 2 real-world cohorts and 2 multicentric randomized controlled trials in China were enrolled, among which 2053 CHB patients were included in the cross-sectional analysis, and 889 CHB patients with paired liver biopsies before and after 72 or 104 weeks of treatment were included in the longitudinal analysis. RESULTS: In the cross-sectional analysis, the areas under the receiver operating characteristic curve of aMAP in diagnosing cirrhosis and advanced fibrosis were 0.788 and 0.757, which were comparable with or significantly higher than those of the fibrosis index based on 4 factors and the aspartate aminotransferase-platelet ratio. The stepwise approach using aMAP and LSM further improved performance in detecting cirrhosis and advanced fibrosis with the smallest uncertainty area (29.7% and 46.2%, respectively) and high accuracy (82.3% and 79.8%, respectively). In the longitudinal analysis, we established a novel model (aMAP-LSM model) by calculating aMAP and LSM results before and after treatment, which had satisfactory performance in diagnosing cirrhosis and advanced fibrosis after treatment (area under the receiver operating characteristic curve, 0.839 and 0.840, respectively), especially for those with a significant decrease in LSM after treatment (vs LSM alone, 0.828 vs 0.748; P < .001 [cirrhosis]; 0.825 vs 0.750; P < .001 [advanced fibrosis]). CONCLUSIONS: The aMAP score is a promising noninvasive tool for diagnosing fibrosis in CHB patients. The aMAP-LSM model could accurately estimate fibrosis stage for treated CHB patients.
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Técnicas de Imagem por Elasticidade , Hepatite B Crônica , Humanos , Masculino , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Estudos Transversais , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Curva ROC , Biópsia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND & AIMS: There is an unmet clinical need for non-invasive tests to diagnose non-alcoholic fatty liver disease (NAFLD) and individual fibrosis stages. We aimed to test whether urine protein panels could be used to identify NAFLD, NAFLD with fibrosis (stage F ≥ 1) and NAFLD with significant fibrosis (stage F ≥ 2). METHODS: We collected urine samples from 100 patients with biopsy-confirmed NAFLD and 40 healthy volunteers, and proteomics and bioinformatics analyses were performed in this derivation cohort. Diagnostic models were developed for detecting NAFLD (UPNAFLD model), NAFLD with fibrosis (UPfibrosis model), or NAFLD with significant fibrosis (UPsignificant fibrosis model). Subsequently, the derivation cohort was divided into training and testing sets to evaluate the efficacy of these diagnostic models. Finally, in a separate independent validation cohort of 100 patients with biopsy-confirmed NAFLD and 45 healthy controls, urinary enzyme-linked immunosorbent assay analyses were undertaken to validate the accuracy of these new diagnostic models. RESULTS: The UPfibrosis model and the UPsignificant fibrosis model showed an AUROC of .863 (95% CI: .725-1.000) and 0.858 (95% CI: .712-1.000) in the training set; and .837 (95% CI: .711-.963) and .916 (95% CI: .825-1.000) in the testing set respectively. The UPNAFLD model showed an excellent diagnostic performance and the area under the receiver operator characteristic curve (AUROC) exceeded .90 in the derivation cohort. In the independent validation cohort, the AUROC for all three of the above diagnostic models exceeded .80. CONCLUSIONS: Our newly developed models constructed from urine protein biomarkers have good accuracy for non-invasively diagnosing liver fibrosis in NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Cirrose Hepática/patologia , Fibrose , Biomarcadores/metabolismo , Biópsia , Fígado/patologiaRESUMO
The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS-CoV-2 may also adversely affect other organ systems. To date, however, there is a very limited understanding of the extent and management of COVID-19-related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extrapulmonary manifestations of COVID-19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes the current understanding of the extrapulmonary complications caused by COVID-19 to improve the management and prognosis of patients with COVID-19.
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COVID-19/complicações , COVID-19/fisiopatologia , Infecções Cardiovasculares/virologia , Gastroenteropatias/virologia , Doenças Hematológicas/virologia , Humanos , Doenças do Sistema Nervoso/virologia , Infecções do Sistema Genital/virologia , Doenças Urológicas/virologiaRESUMO
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
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Fibronectinas , Hepatopatia Gordurosa não Alcoólica , Sarcopenia , Adulto , Biópsia , Fibronectinas/genética , Humanos , Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Sarcopenia/genéticaRESUMO
BACKGROUNDS: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. METHODS: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. RESULTS: A total of 60,965 participants were analyzed, including 11,844 from the US and 51,229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p < 0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. CONCLUSION: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.
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Conjuntos de Dados como Assunto/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Medição de Risco/estatística & dados numéricos , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND AND AIM: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype. METHODS: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin-18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis-4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups). RESULTS: Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin-18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis-4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively). CONCLUSIONS: Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.
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Técnicas de Diagnóstico do Sistema Digestório , Genótipo , Lipase/genética , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIM: There is an immediate need for non-invasive accurate tests for diagnosing liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). Previously, it has been suggested that MACK-3 (a formula that combines homeostasis model assessment-insulin resistance with serum serum aspartate aminotransferase and cytokeratin [CK]18-M30 levels) accurately identifies patients with fibrotic NASH. Our aim was to assess the performance of MACK-3 and develop a novel, non-invasive algorithm for diagnosing fibrotic NASH. METHODS: Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis. RESULTS: Metabolic syndrome (MetS), platelet count and MACK-3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75-0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74-0.87) than that of MACK-3 (AUROC: 0.75, 95%CI 0.68-0.82; P < 0.05) with a NPV of 93.2%. The sequential combination of this nomogram with LSM data avoided the need for liver biopsy in 56.9% of patients. CONCLUSIONS: Our novel nomogram (combining MACK-3, platelet count and MetS) shows promising utility for diagnosing fibrotic NASH. The sequential combination of this nomogram and vibration-controlled transient elastography limits indeterminate results and reduces the number of unnecessary liver biopsies.
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Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Algoritmos , Povo Asiático , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biópsia , Estudos de Coortes , Técnicas de Imagem por Elasticidade , Feminino , Fibrose , Humanos , Resistência à Insulina , Queratina-18/sangue , Masculino , Síndrome Metabólica , Pessoa de Meia-Idade , Nomogramas , Hepatopatia Gordurosa não Alcoólica/patologia , Contagem de Plaquetas , Curva ROCRESUMO
Tumor vascular normalization has been proposed as a therapeutic strategy for malignant neoplasms, which can also interpret the synergistic effect of anti-angiogenesis agents combined with chemotherapy. Apatinib (Apa), a highly selective VEGFR2 inhibitor, attracts much attentions due to its encouraging anticancer activity, especially in the clinical trials of combined treatment. In this study, we investigated whether Apa could promote vascular normalization in tumor in a certain time window. Mice bearing LoVo colon cancer xenograft were orally administrated Apa (150 mg kg-1 per day) for 5, 7, 10, or 12 days. Apa significantly inhibited tumor growth and decreased the microvessel density. Using multi-photon microscopy and electron microscopy, we found that Apa improved tumor vessel morphology by pruning distorted vessel branches and decreased the gap between endothelial cells after a 7-day treatment. Furthermore, Apa decreased vessel leakage and increased pericyte coverage on vascular endothelial cells, suggesting that tumor vessels were more mature and integrated. The intratumoral distribution of adriamycin (ADR) in Apa group was improved from day 7 to 10 without change in plasma drug concentration. Tumor blood perfusion was also increased in this window, and the expression of hypoxia induced factor 1α was downregulated, suggesting the effect of Apa on alleviating tumor hypoxic micro-environment. In conclusion, Apa may improve the effective perfusion of tumor vessels and increase the intratumoral distribution of ADR in a certain time window via normalizing tumor vessels. This normalization window (7 to 10 days of treatment) may contribute to develop a regimen of combined medication in clinic use of Apa.
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Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Piridinas/química , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Injeção Intratimpânica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Piridinas/administração & dosagem , Piridinas/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND Inappropriate use of antibiotics results in antimicrobial resistance and dysbacteriosis. Among critically ill cirrhotic patients, consensus regarding the most optimal prescription strategy for antibiotics use has not been achieved. For these patients, the score for end-stage liver disease (MELD) demonstrated its value in predicting prognosis of cirrhosis. This study investigated use of the MELD score to guide antibiotics choice. MATERIAL AND METHODS We enrolled 1250 patients with cirrhosis. We collected patient information, including antibiotics administration. Linear regression analyses were performed to determine independent predictors of antibiotic administration. Survival curves were constructed based on Cox regression models. Cox proportional hazard models were used to calculate the hazard ratio, shown by forest plots. RESULTS The population was equally stratified into 4 groups based on the MELD score (Q1: MELD <10; Q2: 10≤ MELD <17; Q3: 17≤ MELD <26; Q4: 26≤ MELD). In Q1, all the HR (hazard ratio) related to the duration of antibiotics use demonstrated no statistical significance. In Q2, the HR related to the duration of antibiotics use revealed a successive decrease. In Q3, the HR showed statistical significance only with a duration of antibiotics use of 7 days or more. In Q4, all the HR were statistically significant. As for categories of antibiotics use, whatever the MELD score was, the HR continued to increase with ascending categories. CONCLUSIONS For low MELD score patients (MELD <17), changing the duration of antibiotics use was not associated with a better prognosis. For high MELD score patients (MELD ≥17), longer duration of antibiotics use was associated with a reduction in mortality. Whatever the MELD score was, an increase of number of antibiotic categories was positively associat ed with poor prognosis.
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Antibacterianos/uso terapêutico , Estado Terminal , Doença Hepática Terminal/complicações , Doença Hepática Terminal/tratamento farmacológico , Cirrose Hepática/complicações , Modelos Biológicos , Antibacterianos/administração & dosagem , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-IdadeRESUMO
Although several risk factors for metabolic syndrome (MetS) have been reported, there are few clinical scores that predict its incidence. Therefore, we created and validated a risk score for prediction of 3-year risk for MetS. Three-year follow-up data of 4395 initially MetS-free subjects, enrolled for an annual physical examination from Wenzhou Medical Center were analyzed. Subjects at enrollment were randomly divided into the training and the validation cohort. Univariate and multivariate logistic regression models were employed for model development. The selected variables were assigned an integer or half-integer risk score proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. The predictive performance of the model was tested by computing the area under the receiver operating characteristic curve (AUROC). Four independent predictors were chosen to construct the MetS risk score, including BMI (HR=1.906, 95% CI: 1.040-1.155), FPG (HR=1.507, 95% CI: 1.305-1.741), DBP (HR=1.061, 95% CI: 1.002-1.031), HDL-C (HR=0.539, 95% CI: 0.303-0.959). The model was created as -1.5 to 4 points, which demonstrated a considerable discrimination both in the training cohort (AUROC=0.674) and validation cohort (AUROC=0.690). Comparison of the observed with the estimated incidence of MetS revealed satisfactory precision. We developed and validated the MetS risk score with 4 risk factors to predict 3-year risk of MetS, useful for assessing the individual risk for MetS in medical practice.
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Síndrome Metabólica , Modelos Biológicos , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Breaking the symmetry in the out-of-plane direction in two-dimensional materials to trigger distinctive electronic properties has long been predicted. Inspired by the recent progress in the experimental synthesis of a sandwiched S-Mo-Se structure (Janus SMoSe) at the monolayer limit [Zhang et al., ACS Nano, 2017, 11, 8192-8198], we investigate the transport and electronic structure of two-faced XMoY monolayers (X, Y = O, S, Se and Te) through first-principles calculations. It is found that all the monolayers are semiconductors except OMoTe, which is metallic. Interestingly, the "parents" of OMoTe (MoO2 and MoTe2) are both semiconductors. Further analysis shows that it is the out-of-plane asymmetry-induced strain that results in the metal-semiconductor transition between Janus OMoTe and its parents. By increasing the ratio of O atoms in one face of MoTe2, a progressive decreasing trend of the bandgap, as well as the transition to metallic, is found. In addition, a transition from the direct band gap semiconductor to the indirect one is also observed in the process. This could be used as an effective way to precisely control electronic structures, e.g., the bandgap. Different from other methods, this method uses the intrinsic features of the material, which can persist without the need of additional equipment. Moreover, such a modulating method is expected to be extended to many other transition-metal chalcogenides, showing great application potential.
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BACKGROUND: Inflammation plays an important role in the initiation and progression of acute kidney injury (AKI). However, evidence regarding the prognostic effect of the platelet-to-lymphocyte ratio (PLR), a novel systemic inflammation marker, among patients with AKI is scarce. In this study, we investigated the value of the PLR in predicting the outcomes of critically ill patients with AKI. METHODS: Patient data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III version 1.3. PLR cutoff values were determined using smooth curve fitting or quintiles and were used to categorize the subjects into groups. The clinical outcomes were 30-day and 90-day mortality in the intensive care unit (ICU). Cox proportional hazards models were used to evaluate the association between the PLR and survival. RESULTS: A total of 10,859 ICU patients with AKI were enrolled. A total of 2277 thirty-day and 3112 ninety-day deaths occurred. A U-shaped relationship was observed between the PLR and both 90-day and 30-day mortality, with the lowest risk being at values ranging from 90 to 311. The adjusted HR (95% CI) values for 90-day mortality given risk values < 90 and > 311 were 1.25 (1.12-1.39) and 1.19 (1.08-1.31), respectively. Similar trends were observed for 30-day mortality or when quintiles were used to group patients according to the PLR. Statistically significant interactions were found between the PLR and both age and heart rate. Younger patients (aged < 65 years) and those with more rapid heart rates (≥89.4 beats per minute) tended to have poorer prognoses only when the PLR was < 90, whereas older patients (aged ≥ 65 years) and those with slower heart rates (<89.4 beats per minute) had higher risk only when the PLR was > 311 (P < 0.001 for age and P < 0.001 for heart rate). CONCLUSIONS: The preoperative PLR was associated in a U-shaped pattern with survival among patients with AKI. The PLR appears to be a novel, independent prognostic marker of outcomes in critically ill patients with AKI.
Assuntos
Injúria Renal Aguda/diagnóstico , Contagem de Linfócitos/normas , Contagem de Plaquetas/normas , Prognóstico , Injúria Renal Aguda/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/sangue , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Estimativa de Kaplan-Meier , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Modelos de Riscos ProporcionaisRESUMO
Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary heart disease and tumors by boosting Qi and nourishing Yin. In this study we examined whether SMI could produce direct synergetic effects on the cytoxicity of adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro, and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg·kg-1·3d-1) or PTX (7.5 mg·kg-1·3d-1) with or without SMI (0.01 mL·g-1·d-1) for 13 d. Co-administration of SMI significantly enhanced the chemotherapeutic efficacy of ADR and PTX, whereas administration of SMI alone at the given dosage did not produce visible anti-cancer effects, The chemosensitizing action of SMI was associated with increased concentrations of ADR and PTX in the plasma and tumors. In Caco-2 and LoVo cells in vitro, co-treatment with SMI (2 µL/mL) significantly enhanced the cytotoxicity of ADR and PTX, and resulted in some favorable pharmacokinetic changes in the subcellular distribution of ADR and PTX. In addition, SMI-induced intracellular accumulation of ADR was closely correlated with the increased expression levels of P-glycoprotein in 4 colon cancer cell lines (r2=+0.8558). SMI enhances the anti-cancer effects of ADR and PTX in colon cancers in vivo and in vitro by improving the subcellular distributions of ADR and PTX.
Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Doxorrubicina/farmacologia , Doxorrubicina/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/farmacocinética , Paclitaxel/farmacologia , Paclitaxel/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/sangue , Combinação de Medicamentos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/análise , Humanos , Camundongos , Paclitaxel/sangue , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Nomograms are widely used as predictive tools to predict oncological outcomes intuitively and precisely. The aim of our study was to develop a nomogram for predicting overall survival (OS) of patients with early stage cervical cancer. METHODS: In this retrospective study, the clinical, pathological, and hematological data and prognosis of 795 cervical cancer patients were investigated. We identified and incorporated independent significant prognostic factors for OS to develop a nomogram. The predictive accuracy and discriminative ability were measured by concordance index. RESULTS: By univariable analysis and subsequent multivariable analysis, we identified body mass index, albumin, platelet, leukocyte, tumor differentiation, and the status of the pelvic lymph node (PLN) (all P < 0.05) as independent prognostic factors. The concordance index of the nomogram integrating these 6 variables was 0.74. The calibration curves for probability of 3- and 5-year OS also demonstrated ideal agreement between nomogram prediction and actual observation. CONCLUSIONS: We developed a novel nomogram that can provide prediction of OS for patients with early stage cervical cancer individually. Furthermore, studies are required to validate whether it can be applied to other cohorts.
Assuntos
Nomogramas , Neoplasias do Colo do Útero/mortalidade , China/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Risco , Taxa de Sobrevida , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologiaRESUMO
The prevalence of end-stage renal disease is emerging as a serious worldwide public health problem because of the shortage of donor organs and the need to take lifelong immunosuppressive medication in patients who receive a transplanted kidney. Recently, tissue bioengineering of decellularization and recellularization scaffolds has emerged as a novel strategy for organ regeneration, and we review the critical technologies supporting these methods. We present a summary of factors associated with experimental protocols that may shed light on the future development of kidney bioengineering and we discuss the cell sources and bioreactor techniques applied to the recellularization process. Finally, we review some artificial renal engineering technologies and their future prospects, such as kidney on a chip and the application of three-dimensional and four-dimensional printing in kidney tissue engineering.
Assuntos
Regeneração Tecidual Guiada/métodos , Falência Renal Crônica/terapia , Regeneração , Medicina Regenerativa/tendências , Engenharia Tecidual/métodos , Animais , Reatores Biológicos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Rim/citologia , Rim/patologia , Organogênese , Ratos , Alicerces TeciduaisRESUMO
Allogeneic transplantation is the definitive treatment for patients with end-stage liver disease but is limited by donor shortage and very high cost. Through de-cellularization and re-cellularization methods, re-engineered liver may provide a promising alternative for treating patients with end-stage liver disease. To achieve this, the prevention of the native extracellular matrix ultrastructure plays a central role in de-cellularization protocol; the re-seeding cell types, as well as re-seeding strategies, need more explorations in re-cellularization protocol. Some success of this approach has been published in a rat model; however, the re-engineered liver remains functional in vivo for only several hours, which suggests that the recent protocol may be far from the ideal target. This Review highlights the challenges still to be overcome and presents an overview and summary of methods of de-cellularization and re-cellularization strategies, together with a view on future directions that may lead to the regeneration of a functional liver.