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1.
Clin Mol Hepatol ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839623

RESUMO

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. Methods: We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392 and vitamin D and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. Results: Carriage of the rs495392 A allele had a protective effect on steatosis severity (OR = 0.61, 95% CI: 0.42 - 0.89, P = 0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR = 0.66, 95% CI: 0.45 - 0.98, P = 0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. Conclusions: The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

2.
Endocr Connect ; 10(8): 845-851, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34223825

RESUMO

Background: A prolonged heart rate-corrected QT interval (QTc) has been associated with peripheral artery disease (PAD) in the general population. However, no study to date has identified a link between prolonged QTc and the severity of PAD in patients with diabetes mellitus and foot ulcers (DFUs). This study aimed to investigate this relationship. Methods: This multicenter study enrolled 281 patients with DFUs. The severity of PAD was classified into no severe PAD group (without stenosis or occlusion) and severe PAD group (with stenosis or occlusion) based on duplex ultrasonography. The association of prolonged QTc with severe PAD was evaluated in a multivariable mixed-effect logistic regression model, with the hospital as a random effect. Directed acyclic graphs were used to drive the selection of variables to fit the regression model. Results: Patients with severe PAD had longer QTc than those without. Based on the multivariable mixed-effect logistic regression model, a prolonged QTc was positively associated with severe PAD (odds ratio (OR) = 2.61; 95% CI: 1.07-6.35) and severe DFUs (Wagner grade score ≥ 3) (OR = 2.87; 95% CI: 1.42-5.81). Conclusions: A prolonged QTc was associated with severe PAD in patients with DFUs. Further research is required to ascertain whether the association is causal.

3.
Aliment Pharmacol Ther ; 54(4): 470-480, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34152626

RESUMO

BACKGROUND: Recently, Papatheodoridi et al proposed to refine the Baveno VI elastography dual-cutoffs and introduce an algorithm for the detection of compensated advanced chronic liver disease (cACLD) in asymptomatic European patients with chronic liver diseases. AIMS: To validate the performance of the dual-cutoffs (8/12 kPa) and the proposed algorithm to identify patients with cACLD in three well-characterised Asian nonalcoholic fatty liver disease (NAFLD) cohorts. METHODS: We included 830 patients with biopsy-proven NAFLD. Liver stiffness was measured using transient elastography (FibroScan). RESULTS: cACLD was found in 21.8% of patients. Compared with the original Baveno VI elastography criteria (10/15 kPa), the new cutoffs showed a comparable specificity and a higher sensitivity for identifying cACLD. We developed a simplified risk model incorporating age, liver stiffness value, and platelet count, which outperformed liver stiffness measurement alone in two Chinese cohorts (P = 0.001), and was further validated in a Malaysian cohort (P = 0.04). Overall, the "two-step" screening of cACLD improved classification rates from 73.5% by the original dual-cutoffs to 86.7%. Notably, usage of our simplified risk model resulted in significantly lower false-negative rate than the refined screening approach by Papatheodoridi et al (27.1% vs 41.4%; P = 0.01). CONCLUSIONS: The dual elastography cutoffs of 8 and 12 kPa are more appropriate to identify cACLD in Asian patients with NAFLD. In combination with a simplified risk model in unclassified patients, the two-step approach showed a classification rate of about 85%.


Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Contagem de Plaquetas
4.
J Clin Transl Hepatol ; 9(2): 194-202, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-34007801

RESUMO

Background and Aims: In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The impact of these variants in ethnic Chinese is unknown. The aim of this study was to investigate the potential associations in Chinese patients. Methods: In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology. Results: In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR): 2.93 (1.20-7.17), p=0.019 for the additive model; OR: 3.32 (1.39-7.91), p=0.007 for the recessive model], representing an inverse association as compared to the results from European cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24-0.98), p=0.043 for the additive model; OR: 0.62 (0.40-0.94), p=0.025 for the dominant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis. Conclusions: HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.

5.
Br J Nutr ; 126(6): 813-824, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-33198849

RESUMO

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.

6.
J Med Virol ; 93(1): 323-335, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32648973

RESUMO

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.


Assuntos
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/virologia
7.
BMC Gastroenterol ; 20(1): 139, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375660

RESUMO

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.


Assuntos
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/epidemiologia
8.
J Gastroenterol Hepatol ; 35(10): 1804-1812, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32246876

RESUMO

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.


Assuntos
Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Algoritmos , 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 ROC
9.
J Clin Transl Hepatol ; 8(1): 18-24, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32274342

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions, such as the use of potentially hepatotoxic drugs and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Based on the current evidence from case reports and case series, this review article focuses on the demographic and clinical characteristics, potential mechanisms, and treatment options for COVID-19-related liver dysfunction. This review also describes the geographical and demographic distribution of COVID-19-related liver dysfunction, as well as possible underlying mechanisms linking COVID-19 to liver dysfunction, in order to facilitate future drug development, prevention, and control measures for COVID-19.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32139603

RESUMO

BACKGROUND AND AIM: Imaging-confirmed non-alcoholic fatty liver disease (NAFLD) with normal alanine aminotransferase (nALT) levels is infrequently the subject for further evaluation. Early diagnosis of non-alcoholic steatohepatitis (NASH) is needed to prevent disease progression. Thus, we tested the clinical utility of serum Golgi protein 73 (GP73) levels and developed a new non-invasive score to diagnose NASH in patients with biopsy-confirmed NAFLD and persistent nALT levels. METHODS: Serum GP73 and cytokeratin-18 M30 fragments (CK18-M30) levels were measured in 345 patients with biopsy-proven NAFLD. We developed a new score, named G-NASH model (by incorporating serum GP73), and combined it with serum CK18-M30 measurement in a sequential non-invasive approach to accurately identify NASH among patients with NAFLD and persistent nALT levels. RESULTS: 105 (30.4%) patients had persistent nALT, 53 of whom had histologically confirmed NASH. Both serum GP73 and CK18-M30 levels alone had poor diagnostic accuracy in identifying NASH (55.2% and 51.6%, respectively) in these patients. Conversely, G-NASH model performed better than other established non-invasive scoring systems, and by using our proposed sequential non-invasive approach 82.9% of patients with NASH were correctly identified. CONCLUSIONS: NASH is highly prevalent in patients with NAFLD with persistent nALT levels. The G-NASH model accurately identifies NASH in this patient group.


Assuntos
Alanina Transaminase/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Queratina-18/sangue , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Sensibilidade e Especificidade
14.
J Gastroenterol Hepatol ; 35(6): 1057-1064, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31677195

RESUMO

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.


Assuntos
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-Idade
15.
Eur J Gastroenterol Hepatol ; 32(1): 80-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625959

RESUMO

OBJECTIVE: Insulin resistance (IR) has been established as a major risk factor for nonalcoholic fatty liver disease (NAFLD) where it exerts effects on plasma glucose homeostasis, cellular anabolism, and organ glucose uptake. Owing to paucity of studies focused on peripheral IR in relation to pathological outcome, we aim to investigate homeostatic model assessment of insulin resistance (HOMA-IR) by histological characteristics of NAFLD. METHODS: Liver biopsy of 588 patients was screened. After excluding etiologies other than NAFLD and factors contributing to IR, serum HOMA-IR was compared with patients' histologic features. Univariate and multivariate analyses were conducted to assess their relationship. Area under the receiver operating characteristic (AUROC) was calculated to assess the discriminatory ability of homeostatic model assessment of IR for advanced lobular inflammation (LI). RESULTS: We observed higher serum level of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and low-density lipoprotein as HOMA-IR increased. HOMA-IR is significantly associated with severity of LI (odds ratio = 1.222, 95% confidence interval = 1.135-1.315, P < 0.001), similar association remained after adjusting for age, BMI, hemoglobin A1c, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, high-density lipoprotein, and triglycerides (odds ratio = 1.205, 95% confidence interval = 1.102-1.317, P < 0.001). HOMA-IR is discriminant of LI with AUROC = 0.832 and cutoff = 2.995 (sensitivity = 0.938, specificity = 0.569). CONCLUSION: This study demonstrated a strong and independent association of HOMA-IR with the severity of liver inflammation by histological evaluation in NAFLD patients without diabetes or metabolic syndrome, and its possible role in diagnosis of LI could be translated into clinical assessment of NAFLD patients with uncertainty of nonalcoholic steatohepatitis progression.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Alanina Transaminase , Aspartato Aminotransferases , Humanos , Inflamação , Hepatopatia Gordurosa não Alcoólica/diagnóstico
16.
United European Gastroenterol J ; 7(8): 1124-1134, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31662869

RESUMO

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.


Assuntos
Fibrose/sangue , Fibrose/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto , Antropometria , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biópsia , Plaquetas/citologia , Feminino , Fibrose/diagnóstico , Fibrose/mortalidade , Humanos , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Nomogramas , Hepatopatia Gordurosa não Alcoólica/complicações , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade
17.
J Clin Transl Hepatol ; 7(2): 112-121, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31293910

RESUMO

Background and Aims: The metabolic acid-base disorders have a high incidence of acute kidney injury (AKI) in critically ill cirrhotic patients (CICPs). The aims of our study were to ascertain the composition of metabolic acidosis of CICPs with AKI and explore its relationship with hospital mortality. Methods: Three-hundred and eighty consecutive CICPs with AKI were eligible for the cohort study. Demographic, clinical and laboratory parameters were recorded and arterial acid-base state was analyzed by the Stewart and Gilfix methodology. Results: Net metabolic acidosis, lactic acidosis, acidosis owing to unmeasured anions, acidemia, and dilutional acidosis were less frequent in the non-survival group compared to the survival group of CICPs. The presence of acidemia, acidosis owing to unmeasured anions, and lactic acidosis were independently associated with increased risk of intensive care unit 30-day mortality, with hazard ratios of 2.11 (95% confidence interval (CI): 1.43-3.12), 3.38 (95% CI: 2.36-4.84), and 2.16 (95% CI: 1.47-3.35), respectively. After full adjustment for confounders, the relationship between acidosis owing to unmeasured anions with hospital mortality was still significant, with hazard ratio of 2.29 (95% CI: 1.22-4.30). Furthermore, arterial lactate concentration in combination with chronic liver failure-sequential organ failure assessment and BEUMA had the strongest ability to differentiate 30-day mortality (area under the receiver operating characteristic curve: 0.79, 95% CI: 0.74-0.83). Conclusions: CICPs with AKI exhibit a complex metabolic acidosis during intensive care unit admission. Lactic acidosis and BEUMA, novel markers of acid-base disorders, show promise in predicting mortality rate of CICPs with AKI.

18.
Med Sci Monit ; 25: 5005-5014, 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31278890

RESUMO

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.


Assuntos
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-Idade
19.
Acta Pharmacol Sin ; 40(4): 556-562, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29977004

RESUMO

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.


Assuntos
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 Xenoenxerto
20.
Horm Metab Res ; 50(9): 683-689, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30184562

RESUMO

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.


Assuntos
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 Risco
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