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BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is associated with complications and mortality in patients with coronavirus disease 2019 (COVID-19). However, there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD, despite its high prevalence. Lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage. Therefore, we propose an index based on lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19. AIM: To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases (aspartate aminotransferase/alanine aminotransferase) in patients with COVID-19 and MAFLD [liver fibrosis and nutrition (LNF)-COVID-19 index]. METHODS: In this retrospective cohort study, two cohorts from two different tertiary centers were included. The first was the derivation cohort to obtain the score cutoffs, and the second was the validation cohort. We included hospitalized patients with severe COVID-19 and MAFLD. Liver steatosis was evaluated by computed tomography scan. Area under the receiver operating characteristic (ROC) curve analysis and survival analysis were used. RESULTS: In the derivation cohort, 44.6% had MAFLD; ROC curve analysis yielded a LFN-COVID-19 index > 1.67 as the best cutoff, with a sensitivity of 78%, specificity of 63%, negative predictive value of 91% and an area under the ROC curve of 0.77. In the multivariate analysis, the LFN-COVID-19 index > 1.67 was independently associated with the development of acute kidney injury (odds ratio: 1.8, 95% confidence interval: 1.3-2.5, P < 0.001), orotracheal intubation (odds ratio: 1.9, 95% confidence interval: 1.4-2.4, P < 0.001), and death (odds ratio: 2.86, 95% confidence interval: 1.6-4.5, P < 0.001) in both cohorts. CONCLUSION: LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19, which could be useful for the MAFLD population.
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COVID-19 , Fígado Gorduroso , Hepatopatia Gordurosa não Alcoólica , Humanos , COVID-19/complicações , Alanina Transaminase , Estudos Retrospectivos , Fígado Gorduroso/complicações , Aspartato Aminotransferases , Prognóstico , Lactato Desidrogenases , Oxirredutases , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
Metabolic diseases are highly prevalent worldwide and have been associated with adverse clinical outcomes, including mortality, in patients developing coronavirus disease (COVID-19). Because of the close relationship between metabolic diseases such as type 2 diabetes mellitus and obesity and the presence of metabolic-associated fatty liver disease (MAFLD), a high number of cases of patients affected by both MAFLD and COVID-19 would be expected, especially in high-risk populations. Some studies have shown an increased risk of adverse clinical outcomes, viral shedding, and deep vein thrombosis, especially in patients with MAFLD- related liver fibrosis. The predisposition to poor outcomes and severe acute respiratory syndrome coronavirus 2 infection in patients with MAFLD could be secondary to mechanisms common to both, including preexisting systemic chronic inflammation, endothelial dysfunction, and involvement of the renin-angiotensin system. Because of the increased risk of adverse outcomes, MAFLD should be screened in all patients admitted for COVID-19. Available computed tomography scans could be of help, assessment of liver fibrosis is also recommended, favoring noninvasive methods to limit the exposure of healthcare workers. Liver involvement in this population ranges from abnormalities in liver chemistry to hepatic steatosis in postmortem biopsies. Finally, preventive measures should be strongly advocated in patients already known to have MAFLD, including the use of telemedicine and vaccination in addition to general measures.
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COVID-19 , Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/etiologia , Humanos , SARS-CoV-2RESUMO
BACKGROUND: Metabolic diseases are risk factors for severe Coronavirus disease (COVID-19), which have a close relationship with metabolic dysfunction-associated fatty liver disease (MAFLD). AIMS: To evaluate the presence of MAFLD and fibrosis in patients with COVID-19 and its association with prognosis. METHODS: Retrospective cohort study. In hospitalized patients with COVID-19, the presence of liver steatosis was determined by computed tomography scan (CT). Liver fibrosis was assessed using the NAFLD fibrosis score (NFS score), and when altered, the AST to platelet ratio index (APRI) score. Mann-Whitney U, Student´s t-test, logistic regression analysis, Kaplan-Meier curves and Cox regression analysis were used. RESULTS: 432 patients were analyzed, finding steatosis in 40.6%. No differences in pulmonary involvement on CT scan, treatment, or number of days between the onset of symptoms and hospital admission were found between patients with and without MAFLD. The presence of liver fibrosis was associated with higher severity scores, higher levels of inflammatory markers, requirement of mechanical ventilation, incidence of acute kidney injury (AKI), and higher mortality than patients without fibrosis. CONCLUSION: The presence of fibrosis rather than the presence of MAFLD is associated with increased risk for mechanical ventilation, development of AKI, and higher mortality in COVID-19 patients.
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COVID-19 , Fígado Gorduroso , Cirrose Hepática , Fígado , Respiração Artificial/estatística & dados numéricos , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Plaquetas/patologia , COVID-19/sangue , COVID-19/complicações , COVID-19/mortalidade , COVID-19/terapia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/metabolismo , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/metabolismo , Testes de Função Hepática/métodos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodosRESUMO
Retinol plays a significant role in several physiological processes through their nuclear receptors, whose expression depends on retinol cytoplasmic concentration. Loss of expression of nuclear receptors and low retinol levels have been correlated with lung cancer development. Stimulated by retinoic acid 6 (STRA6) is the only described cell membrane receptor for retinol uptake. Some chronic diseases have been linked with specific polymorphisms in STRA6. This study aimed to evaluate four STRA6 single nucleotide polymorphisms (SNPs) (rs4886578, rs736118, rs351224, and rs97445) among 196 patients with locally-advanced and metastatic non-small cell lung cancer (NSCLC) patients. Genotyping, through a validated SNP assay and determined using real time-PCR, was correlated with clinical features and outcomes. NSCLC patients with a TT SNP rs4886578 and rs736118 genotype were more likely to be >60 years, non-smokers, and harboring EGFR mutations. Patients with a TT genotype compared with a CC/CT SNP rs974456 genotype had a median progression-free survival (PFS) of 3.2 vs. 4.8 months, p = 0.044, under a platinum-based regimen in the first-line. Furthermore, patients with a TT rs351224 genotype showed a prolonged overall survival (OS), 47.5 months vs. 32.0 months, p = 0.156. This study showed a correlation between clinical characteristics, such as age, non-smoking history, and EGFR mutational status and oncological outcomes depending on STRA6 SNPs. The STRA6 TT genotype SNP rs4886578 and rs736118 might be potential biomarkers in locally-advanced and metastatic NSCLC patients.
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BACKGROUND: The National Program for Chagas disease was implemented in Bolivia in 2006, and it greatly decreased the number of infections through vector control. Subsequently, a treatment regimen of benznidazole (BNZ) was started in seropositive school-age children living in certified vector control areas. METHODS AND FINDINGS: We conducted a 12-month follow-up study and seven blood samples were taken during and after the treatment. Serology, conventional diagnostic PCR (cPCR) and quantitative Real-time PCR (qPCR) were performed. Plasma Th1/Th2/Th17 cytokines levels were also determined. Approximately 73 of 103 seropositive children complied with BNZ, with three interruptions due to side effects. To evaluate each individual's treatment efficacy, the cPCR and qPCR values during the final 6 months of the follow-up period were observed. Among 57 children who completed follow-up, 6 individuals (11%) showed both cPCR(+) and qPCR(+) (non reactive), 24 (42%) cPCR(-) but qPCR(+) (ambiguous) and 27 (47%) cPCR(-) and qPCR(-) (reactive). Within 14 Th1/Th2/Th17 cytokines, IL-17A showed significantly higher levels in seropositive children before the treatment compared to age-matched seronegative children and significantly decreased to the normal level one-year after. Moreover, throughout the follow-up study, IL-17A levels were positively co-related to parasite counts detected by qPCR. At the 12 months' time point, IL-17A levels of non-reactive subjects were significantly higher than either those of reactive or ambiguous subjects suggesting that IL-17A might be useful to determine the reactivity to BNZ treatment. CONCLUSIONS: Plasma levels of IL-17A might be a bio-marker for detecting persistent infection of T. cruzi and its chronic inflammation.
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Doença de Chagas/tratamento farmacológico , Interleucina-17/sangue , Nitroimidazóis/uso terapêutico , Resultado do Tratamento , Adolescente , Biomarcadores/sangue , Bolívia , Doença de Chagas/sangue , Criança , Pré-Escolar , Citocinas , Feminino , Seguimentos , Humanos , Masculino , Nitroimidazóis/sangue , Reação em Cadeia da Polimerase/métodos , Tripanossomicidas/sangue , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
Understanding the microstructure in heterostructured nanoparticles is crucial to harnessing their properties. Although microscopy is ideal for this purpose, it allows for the analysis of only a few nanoparticles. Thus, there is a need for structural methods that take the whole sample into account. Here, a novel bulk-approach based on the combined analysis of synchrotron X-ray powder diffraction with whole powder pattern modeling, Rietveld and pair distribution function is presented. The microstructural temporal evolution of FeO/Fe3 O4 core/shell nanocubes is studied at different time intervals. The results indicate that a two-phase approach (FeO and Fe3 O4 ) is not sufficient to successfully fit the data and two additional interface phases (FeO and Fe3 O4 ) are needed to obtain satisfactory fits, i.e., an onion-type structure. The analysis shows that the Fe3 O4 phases grow to some extent (≈1 nm) at the expense of the FeO core. Moreover, the FeO core progressively changes its stoichiometry to accommodate more oxygen. The temporal evolution of the parameters indicates that the structure of the FeO/Fe3 O4 nanocubes is rather stable, although the exact interface structure slightly evolves with time. This approach paves the way for average studies of interfaces in different kinds of heterostructured nanoparticles, particularly in cases where spectroscopic methods have some limitations.
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OBJECTIVES: To draw evidence-based conclusions about the epidemiology, drivers, and management of diabetes in Panama based on a literature review and original analyses of large databases. METHODS: A search about diabetes in Panama was conducted through PubMed. We used the final reports of 2 studies: the first Survey of Health and Life Quality, 2007, and the first Survey of Risk Factors Associated to Cardiovasular Diseases, 2010-2011, conducted in Panama and analyzed the databases. We reviewed the approach adopted by the Panamanian Social Security institution and the diabetes national guidelines published by the Panamanian Ministry of Health. FINDINGS: The prevalence of diabetes, as estimated in 1 database (ENSCAVI), was 5.4% (4.3% men; 6.0% women; OR = 1.41 [confidence interval 1.26-1.59]; P < 0.0001), with the highest prevalence in urbanized regions. In another database (PREFREC), prevalence was 9.5% (10.3% men and 9.1% women), again higher in urbanized regions, but also in males, older adults, and Afro-Panamanians. Obesity, abdominal obesity, physical inactivity, family history of diabetes, high blood pressure, and triglycerides ≥ 150 mg/dL were associated as risk factors for diabetes in both genders (P < 0.0001). Total cholesterol ≥ 200 mg/dL and high-density lipoprotein cholesterol < 40 mg/dL were risk factors in men (P < 0.0001). In the last 5 years, diabetes was ranked between the sixth and fifth cause of death in Panama. In response, the Panamanian Social Security created the "Program for Prevention and Control of Diabetes" to strengthen primary health care. CONCLUSIONS: Diabetes is a serious national public health threat in Panama. To address this problem in a public health modality, information from large databases was analyzed and presented to the Panamanian Ministry of Health to prompt constructive policy change to enhance diabetes prevention.
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Diabetes Mellitus/epidemiologia , Triglicerídeos/sangue , Diabetes Mellitus/etnologia , Diabetes Mellitus/mortalidade , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Sobrepeso/epidemiologia , Panamá/epidemiologia , Prevalência , Fatores de Risco , População Rural , População UrbanaRESUMO
AIM: In previous CYP2D6 genotyping studies in Mexican-Amerindians a very low frequency of poor metabolizers (PMs) has been reported. Moreover, ultrarapid metabolizers (UMs) status has only been analyzed in some groups from Northern Mexico. MATERIALS & METHODS: In the present study we evaluated the hypothesis of low frequency of PMs in Mexican-Amerindians in Southern Mexican populations from Chiapas (Lacandones [ML] vs Mestizos [MM]). The frequency of UMs is also reported. CYP2D6 alleles *2, *3, *4, *5, *6, *10, *17, *35 and *41 and copy number variations were analyzed in 154 ML and 100 MM healthy volunteers. RESULTS: The PM frequency was 0% in MLs and 1% in MMs, and for UMs was 2.6% in MLs and 3% in MMs. CONCLUSION: The present data support previous findings reporting a very low frequency of CYP2D6 PMs in Mexican-Amerindians. Furthermore, the predicted UM phenotype in both MMs and MLs was lower than those reported for most Mexican populations.