Artigos e Materiais de Revistas Científicas - LIM/07

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.


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  • article 1 Citação(ões) na Scopus
    Immune Evasion of SARS-CoV-2 Omicron Subvariants XBB.1.5, XBB.1.16 and EG.5.1 in a Cohort of Older Adults after ChAdOx1-S Vaccination and BA.4/5 Bivalent Booster
    (2024) MACHADO, Rafael Rahal Guaragna; CANDIDO, erika Donizetti; AGUIAR, Andressa Simoes; CHALUP, Vanessa Nascimento; SANCHES, Patricia Romao; DORLASS, Erick Gustavo; AMGARTEN, Deyvid Emanuel; PINHO, Joao Renato Rebello; DURIGON, Edison Luiz; OLIVEIRA, Danielle Bruna Leal
    The recently emerged SARS-CoV-2 Omicron sublineages, including the BA.2-derived XBB.1.5 (Kraken), XBB.1.16 (Arcturus), and EG.5.1 (Eris), have accumulated several spike mutations that may increase immune escape, affecting vaccine effectiveness. Older adults are an understudied group at significantly increased risk of severe COVID-19. Here we report the neutralizing activities of 177 sera samples from 59 older adults, aged 62-97 years, 1 and 4 months after vaccination with a 4th dose of ChAdOx1-S (Oxford/AstraZeneca) and 3 months after a 5th dose of Comirnaty Bivalent Original/Omicron BA.4/BA.5 vaccine (Pfizer-BioNTech). The ChAdOx1-S vaccination-induced antibodies neutralized efficiently the ancestral D614G and BA.4/5 variants, but to a much lesser extent the XBB.1.5, XBB.1.16, and EG.5.1 variants. The results showed similar neutralization titers between XBB.1.16 and EG.5.1 and were lower compared to XBB.1.5. Sera from the same individuals boosted with the bivalent mRNA vaccine contained higher neutralizing antibody titers, providing a better cross-protection against Omicron XBB.1.5, XBB.1.16 and EG.5.1 variants. Previous history of infection during the epidemiological waves of BA.1/BA.2 and BA.4/BA.5, poorly enhanced neutralization activity of serum samples against XBBs and EG.5.1 variants. Our data highlight the continued immune evasion of recent Omicron subvariants and support the booster administration of BA.4/5 bivalent vaccine, as a continuous strategy of updating future vaccine booster doses to match newly emerged SARS-CoV-2 variants.
  • article 1 Citação(ões) na Scopus
    Seroprevalence of hepatitis E virus in patients with chronic liver disease
    (2024) ARAUJO, Lilian Rose Maia Gomes de; BATISTA, Andrea Doria; COELHO, Maria Rosangela Cunha Duarte; SANTOS, Joelma Carvalho; CUNHA, Gabriel Galindo; LEAL, Gabriela Rodrigues Aguiar; PINHO, Joao Renato Rebello; DOMINGUES, Ana Lucia Coutinho; LOPES, Edmundo Pessoa
    IntroductionThe seroprevalence of hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is little known in Brazil. Studies have suggested that HEV may harmfully influence the course of CLD, with a higher risk of progression to cirrhosis.ObjectiveTo estimate the prevalence of the anti-HEV antibody (IgG) in patients with CLD and to describe demographic data and risk factors, as well as clinical-laboratory and ultrasound parameters.Patients and methodsCross-sectional study that included 227 patients with CLD followed at a referral outpatient clinic from June 2022 to March 2023. The patients were investigated clinically and tested for liver functions, anti-HEV IgG and, in positive cases, for HEV-RNA. Ultrasonography of the upper abdomen was also carried out.ResultsInvestigation of 227 patients (50 with hepatitis B, 49 with nonalcoholic fatty liver disease, 33 with hepatitis C, 17 with alcoholic liver disease, 16 with schistosomiasis and 62 with mixed disease), 55.5% were female, with an average age of 57 +/- 13 years; 37.9% had liver cirrhosis. Seven patients (3.08%) presented anti-HEV positive and HEV-RNA negative. Ultrasound identified association between anti-HEV and contact with pigs, presence of gynecomastia or palmar erythema, lower platelet count, higher APRI and FIB-4 values, and splenomegaly.ConclusionAlthough the prevalence of anti-HEV in patients with CLD was low in this study, the antibody was observed more frequently in cases with a history of contact with pigs and with clinical-laboratory or imaging evidence of more advanced chronic liver disease.
  • article 3 Citação(ões) na Scopus
    Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)
    (2023) MOREIRA, Rodrigo Oliveira; VALERIO, Cynthia Melissa; VILLELA-NOGUEIRA, Cristiane Alves; CERCATO, Cintia; GERCHMAN, Fernando; LOTTENBERG, Ana Maria Pita; GODOY-MATAS, Amelio Fernando; OLIVEIRA, Ricardo de Andrade; MELLO, Carlos Eduardo Brandao; ALVARES-DA-SILVA, Mario Reis; LEITE, Nathalie Carvalho; COTRIM, Helma Pinchemel; PARISI, Edison Roberto; SILVA, Giovanni Faria; MIRANDA, Paulo Augusto Carvalho; HALPERN, Bruno; OLIVEIRA, Claudia Pinto
    Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.
  • article 0 Citação(ões) na Scopus
    Brazilian Landscape of Hepatocellular Carcinoma
    (2023) FONSECA, Leonardo G.; CHEN, Andre T. C.; OLIVEIRA, Irai S. de; CHAGAS, Aline L.; KRUGER, Jaime A. P.; CARRILHO, Flair J.
    The incidence of hepatocellular carcinoma (HCC) is expected to increase in the coming years, and strategies to mitigate the burden of this disease are needed in different regions. Geographic variations in epidemiology and risk factors, such as viral hepatitis and metabolic disease, pose challenges in adopting programs for early detection programs and management of patients with HCC. Brazil, like other countries, has high economic and social inequality, with heterogeneous access to health care. Viral hepatitis is themain risk factor but there is growing awareness of fatty liver disease. Risk factor monitoring and screening programs are unmet priorities because patients are often diagnosed at later stages. Advances in the management of patients with HCC have been made in recent years, including new tools for selecting patients for liver transplantation, sophisticated surgical techniques, and new systemic agents. High-volume academic centers often achieve favorable results through the adoption and application of established treatments, but this is not a reality in most regions of Brazil, because of disparities in wealth and resources. As HCC management requires a coordinated and multidisciplinary team, the role of local referral centers in decentralizing access to treatments and promoting health education in different regions should be encouraged and supported.
  • article 0 Citação(ões) na Scopus
    Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease
    (2024) MICHALCZUK, Matheus Truccolo; LONGO, Larisse; KEINGESKI, Melina Belen; BASSO, Bruno de Souza; GUERREIRO, Gabriel Tayguara Silveira; FERRARI, Jessica T.; VARGAS, Jose Eduardo; OLIVEIRA, Claudia P.; URIBE-CRUZ, Carolina; CERSKI, Carlos Thadeu Schmidt; FILIPPI-CHIELA, Eduardo; ALVARES-DA-SILVA, Mario Reis
    BACKGROUND Prevalence of hepatocellular carcinoma (HCC) is increasing, especially in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). AIM To investigate rifaximin (RIF) effects on epigenetic/autophagy markers in animals. METHODS Adult Sprague-Dawley rats were randomly assigned (n = 8, each) and treated from 5-16 wk: Control [standard diet, water plus gavage with vehicle (Veh)], HCC [high-fat choline deficient diet (HFCD), diethylnitrosamine (DEN) in drinking water and Veh gavage], and RIF [HFCD, DEN and RIF (50 mg/kg/d) gavage]. Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained. RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis, and cirrhosis, but three RIF-group did not develop HCC. Comparing animals who developed HCC with those who did not, miR-122, miR-34a, tubulin alpha-1c (Tuba-1c), metalloproteinases-2 (Mmp2), and metalloproteinases-9 (Mmp9) were significantly higher in the HCC-group. The opposite occurred with Becn1, coactivator associated arginine methyltransferase-1 (Carm1), enhancer of zeste homolog-2 (Ezh2), autophagy-related factor LC3A/B (Map1 Lc3b), and p62/sequestosome-1 (p62/SQSTM1)-protein. Comparing with controls, Map1 Lc3b, Becn1 and Ezh2 were lower in HCC and RIF-groups (P < 0.05). Carm1 was lower in HCC compared to RIF (P < 0.05). Hepatic expression of Mmp9 was higher in HCC in relation to the control; the opposite was observed for p62/Sqstm1 (P < 0.05). Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control (P = 0.024). There was no difference among groups for Tuba-1c, Aldolase-B, alpha-fetoprotein, and Mmp2 (P > 0.05). miR-122 was higher in HCC, and miR-34a in RIF compared to controls (P < 0.05). miR-26b was lower in HCC compared to RIF, and the inverse was observed for miR-224 (P < 0.05). There was no difference among groups regarding miR-33a, miR-143, miR-155, miR-375 and miR-21 (P > 0.05). CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.
  • article 2 Citação(ões) na Scopus
    Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism
    Introduction: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. Methods: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. Results: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. Conclusion: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.
  • article 0 Citação(ões) na Scopus
    Potential Beneficial Effect of Rifaximin in the Prevention of Hepatocellular Carcinoma through the Modulation of the Microbiota in an Experimental Model of Non-alcoholic Fatty Liver Disease
    (2023) FERRARI, J. Tonin; GUERREIRO, G. Tayguara Silveira; LONGO, L.; SILVEIRA, T. R. D.; CERSKI, C. T. Schmidt; TOZAWA, E.; OLIVEIRA, C. P.; ÁLVARES-DA-SILVA, M. R.; URIBE-CRUZ, C.
    Summary Aim. To evaluate the effects of rifaximin through microbiota modulation in a model of hepatocellular carcinoma secondary to non-alcoholic fatty liver disease. Methods. Three groups of 8 adult male Sprague-Dawley rats each were divided as follows: the HCC group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine as a carcinogen, the hepatocellular carcinoma treated group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine and treated with rifaximin and the control group: animals fed standard diet and water. The rats were euthanized after 16 weeks. We performed analyses of liver pathology for non-alcoholic fatty liver disease severity and cancer grading, gene expression in intestinal and hepatic tissues and fecal microbiota. Results. All animals in the hepatocellular carcinoma group had non-alcoholic fatty liver disease and developed hepatocellular carcinoma lesions. Rifaximin animals showed less intense non-alcoholic fatty liver disease (assessed by non-alcoholic fatty liver disease activity score [NAS]) compared to the hepatocellular carcinoma group. Both the hepatocellular carcinoma and hepatocellular carcinoma + rifaximin groups showed areas of fibrosis as assessed by picrosirius red. Three animals in the rifaximin group did not develop cancerous lesions. Gut microbiota analyses revealed differences in diversity and composition in the control group vs hepatocellular carcinoma and rifaximin groups. Twelve differentially abundant genera were identified between the hepatocellular carcinoma and rifaximin groups. In the rifaximin group, gene expression of intestinal tight junctions decreased. Conclusions. In a rodent model of non-alcoholic fatty liver disease-related hepatocellular carcinoma, rifaximin reduces the histological severity of non-alcoholic fatty liver disease and the occurrence of hepatocellular carcinoma, probably by modulating the gut microbiota independently of markers of intestinal permeability.
  • article 0 Citação(ões) na Scopus
    Investigation of etiology of community-acquired pneumonia in hospitalized patients in a tertiary hospital of Sao Paulo City, Brazil
    (2023) JOELSONS, Daniel; ALENCAR, Cecilia Salete; PINHO, Joao Renato Rebello; HO, Yeh-Li
    Background: Community-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations. Methods: The aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens. Results: A total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy. Conclusion: Our study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics. (c) 2023 Sociedade Brasileira de Infectologia.
  • article 0 Citação(ões) na Scopus
    Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D
    (2023) REUTER, Tania; GOMES-GOUVEA, Michele Soares; CHUFFI, Samira; DUQUE, Ulisses Horst; PERINI, Waltesia; AZEVEDO, Raymundo Soares; PINHO, Joao Renato Rebello; LEWIS-XIMENEZ, Lia L.; VILLAR, Livia Melo; ESPUL, Carlos Alberto; PUJOL, Flor H.; ROMAN, Sonia
    In Brazil, hepatitis B virus endemicity is low, moderate, or high in some areas, such as Espirito Santo State in the southeast region. In this study, we intend to characterize the basal core promoter (BCP) and pre-core region (PC) variants and their association with clinical/epidemiological disease patterns in patients infected with genotypes A and D. The study included 116 chronic hepatitis B patients from Espirito Santo State, Southeast Brazil, infected with genotypes A and D. Basal core promoter (BCP) and pre-core mutations were analyzed in these patients. The frequency of BCP and PC mutations was compared with age, HBeAg status, HBV genotype and subgenotype, HBV-DNA level, clinical classification, and transmission route. HBeAg-negative status was found in 101 (87.1%) patients: 87 (75.0%) were infected with genotype A (A1 = 85; A2 = 2) and 29 (25.0%) were infected with genotype D (D3 = 24; D4 = 3; D2 = 2). BCP + PC variants altogether were more frequent (48.1%) in genotype D than in genotype A strains (6.0%) (p < 0.001). When this evaluation was performed considering the cases that presented only the A1762T and/or G1764A (BCP) mutations, it was observed that the frequency was higher in genotype A (67.5%) compared to genotype D (7.4%) (p < 0.001). On the other hand, considering the samples with mutations only in positions G1896A and/or G1899A (PC), the frequency was higher in genotype D (75.8%) than in genotype A (6.9%) (p < 0.001). Interestingly, HBV DNA was lower than 2000 IU/mL especially when both BCP/PC mutations were present (p < 0.001) or when only PC mutations were detected (p = 0.047), reinforcing their role in viral replication.
  • article 0 Citação(ões) na Scopus
    Clinical Aspects and Etiologic Investigation of Pediatric Patients With Acute Liver Failure
    (2023) LUGLIO, Michele; MARQUES, Tatiana de Carvalho Silva; PEREIRA, Maria Fernanda Badue; DELGADO, Artur Figueiredo; CARVALHO, Werther Brunow de; TANNURI, Ana Cristina Aoun; SANDY, Natascha Silva; LITVINOV, Nadia; PAULA, Camila Sanson Yoshino de; SANTOS, Ariane Guissi dos; LAZARI, Carolina dos Santos; GOUVEA, Michele Soares Gomes; PAULA, Anderson Vicente de; MENDOZA, Tania Regina Tozetto; TANIGAWAH, Ryan Yukimatsu; LIMAH, Fabiana Roberto; HIRAYAMAH, Andre Bubna; SANTOS, Isabela Gusson Galdino dos; PINHOG, Joao Renato Rebello; SABINOG, Ester Cerdeira; MENDES-CORREAHG, Maria Cassia; ALVESH, Venancio Avancini Ferreira; MARQUESC, Heloisa Helena de Sousa
    A new outbreak of hepatitis of unknown origin raised awareness in the international community. A few reports have attempted to associate new cases with adenovirus infection and the immunologic effects of previous SARS-CoV-2 infections through a superantigen mechanism. Moreover, according to a case series, viral isolates were identified in 7 of 10 cases of pediatric patients with hepatitis of unknown origin and acute liver failure. Adenovirus was detected by respiratory secretion polymerase chain reaction in 2 patients, with neither presenting with SARS-CoV-2 acute infection. Clinical and laboratory descriptions and cross-referencing epidemiologic and pathophysiological data can help identify possible disease etiologies.
  • article 0 Citação(ões) na Scopus
    Lysosomal Acid Lipase Deficiency in the Etiological Investigation of Cryptogenic Liver Disease in Adults: A Multicenter Brazilian Study
    (2023) CANDOLO, Aline Coelho Rocha; CANCADO, Guilherme Grossi Lopes; ZITELLI, Patricia Momoyo; MAZO, Daniel Ferraz de Campos; OLIVEIRA, Claudia Pinto Marques; CUNHA-SILVA, Marlone; GRECA, Raquel Dias; ARAUJO, Roberta Chaves; ALUSTAU, Amanda Sacha Paulino Tolentino; COUTO, Claudia Alves; NARDELLI, Mateus Jorge; LIMA, Roque Gabriel Rezende de; FARIAS, Alberto Queiroz; CARRILHO, Flair Jose; PESSOA, Mario Guimaraes
    Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of cryptogenic liver disease. Methods: A large multicenter cross-sectional study was conducted, which included 135 patients with cryptogenic liver disease from four liver centers in Brazil. All patients were submitted to the investigation of LAL enzyme activity on dried blood spots. Results: Three patients (two female) presented levels of LAL below the reference limit, compatible with LAL-D (2.2%). They had a mean age of 43.9 +/- 10.1 years and a mean body-mass index (BMI) of 23.1 +/- 1.7 kg/m2. The mean serum levels of glucose, HDL-cholesterol, and triglycerides were 89.7 +/- 3.2, 21.7 +/- 3.2, and 206.7 +/- 25.5 mg/dL, respectively. All patients had duodenal polyposis with xanthomatous macrophages. LAL-D investigation should be considered for individuals with chronic liver disease of an unknown etiology, especially with a normal BMI, high triglycerides, and low-HDL-cholesterol levels. The identification of LAL-D patients is extremely important since enzyme replacement therapy with Sebelipase Alfa significantly increases their survival.
  • article 2 Citação(ões) na Scopus
    Liver transplantation in Latin America: reality and challenges
    Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant pro-grams and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation. Addressing these shortcomings will require national shifts aimed at improving infrastructure, increasing awareness of organ donation, training medical personnel, and providing equitable access to care for all patients.
  • article 0 Citação(ões) na Scopus
    Evaluation of oxidative stress in an experimental model of Crohn's disease treated with hyperbaric oxygen therapy
    (2023) NAKUTIS, Fernanda Serafim; NISHITOKUKADO, Ieda; SANTOS, Fabiana Maria dos; ORTIZ-AGOSTINHO, Carmen Lucia; ALENCAR, Daniel Teixeira de; ACHTSCHIN, Cassiana Ganem; NUNES, Valeria Sutti; LEITE, Andre Zonetti Arruda; SIPAHI, Aytan Miranda
    Introduction: Treatments of Inflammatory Bowel Disease (IBD) are able to control symptoms in most cases, how-ever, a fraction of patients do not improve or have a loss of response to treatments, making it important to explore new therapeutic strategies. Hyperbaric oxygen therapy (HBO) may represent one of them. The aim of this study was to evaluate the effects of HBO therapy in an experimental model of IBD. Methods: Sixty male BALBc mice were divided into six groups. Group 1 was colitis-induced with trinitrobenzene sulfonic acid (TNBS) + ethanol, group 2 received TNBS + ethanol plus HBO, group 3 received only ethanol, group 4 received ethanol plus HBO, group 5 received saline solution, and group 6 received saline solution plus HBO. HBO was performed for four days, subsequently, the mice were evaluated daily. At the end of the study, samples from the intestine were collected for histological analysis as well as for measurement of antioxidant enzymes and cytokine levels. Results: HBO significantly improved the clinical and histological status of the animals. Treatment with HBO increased the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in all of the groups; moreover, the difference was only significant between the TNBS and TNBS + HBO groups and treatments promoted a reduction in the proinflammatory cytokines IFN-gamma, IL-12, IL-17 and TNF-alpha and increased the anti-inflammatory cytokines IL-4 and IL-10, with no changes in IL-13. Conclusion: HBO effectively treats TNBS-induced colitis by increasing the activity of antioxidant enzymes and modulating cytokine profiles.
  • article 2 Citação(ões) na Scopus
    Neoadjuvant and adjuvant systemic treatment for hepatocellular carcinoma
    (2021) MATHIAS-MACHADO, Maria Cecilia; FONSECA, Leonardo G. da
    Hepatocellular carcinoma (HCC) is a highly lethal malignancy, and few patients are candidates for curative-intended therapies. The mainstay of curative treatment in HCC is surgical resection, ablation, and transplantation. However, rates of recurrence are high, and there is no established approach to reduce the risk of recurrence and mortality. We discuss the available data and current landscape of (neo)adjuvant therapies aimed at decreasing recurrence risk and improving overall survival, including liver-directed therapies, tyrosine kinase inhibitors, and immunotherapy. Neoadjuvant strategies aimed at downstaging advanced HCC to enable local treatment and minimize the risk of recurrence using novel agents are also a topic of interest in current research. The improvements achieved in the advanced stages with immune-checkpoint inhibitors are priming ongoing trials that address potential future directions for both adjuvant and neoadjuvant strategies that may change the treatment paradigm of HCC in the near future.
  • article 2 Citação(ões) na Scopus
    COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS
    (2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Caroline Toledo do; BRITO, Jose Mara de; ANTONANGELO, Leila; FARIA, Caroline Silverio; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; SEELAENDER, Marilia; CASTRO, Gabriela Salim de; LIMA, Joanna D. C. C.; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz da; DOLHNIKOFF, Marisa; MAUAD, Thais
    BackgroundLung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS.MethodsWe have quantified different ECM elements and TGF-beta expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile.ResultsWe observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-beta, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-beta was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course.ConclusionsFatal COVID-19 is associated with an early TGF-beta expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.
  • article 2 Citação(ões) na Scopus
    Association of UCP3 Polymorphisms with Nonalcoholic Steatohepatitis and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease Brazilian Patients
    (2022) TODA-OTI, Karla Sawada; STEFANO, Jose Tadeu; CAVALEIRO, Ana Mercedes; CARRILHO, Flair Jose; CORREA-GIANELLA, Maria Lucia; OLIVEIRA, Claudia Pinto Marques de Souza de
    Background: We investigated the possible association of uncoupling protein 3 gene (UCP3) single nucleotide polymorphisms (SNPs) with nonalcoholic steatohepatitis (NASH) and metabolic syndrome (MetS) in nonalcoholic fatty liver disease (NAFLD) Brazilian patients.Methods: UCP3 SNPs rs1726745, rs3781907, and rs11235972 were genotyped in 158 biopsy-proven NAFLD Brazilian patients. Statistics was performed with JMP, R, and SHEsis softwares.Results: The TT genotype of rs1726745 was associated with less occurrence of MetS (P = 0.006) and with lower body mass index (BMI) in the entire NAFLD sample (P = 0.01) and in the NASH group (P = 0.02). The rs1726745-T was associated with lower values of AST (P = 0.001), ALT (P = 0.0002), triglycerides (P = 0.01), and total cholesterol (P = 0.02) in the entire NAFLD sample. Between groups, there were lower values of aminotransferases strictly in individuals with NASH (AST, P = 0.002; ALT, P = 0.0007) and with MetS (AST, P = 0.002; ALT, P = 0.001). The rs3781907-G was associated with lower GGT elevation values in the entire NAFLD sample (P = 0.002), in the NASH group (P = 0.004), and with MetS group (P = 0.003) and with protection for advanced fibrosis (P = 0.01). The rs11235972-A was associated with lower GGT values in the entire NAFLD sample (P = 0.006) and in the NASH group (P = 0.01) and with MetS group (P = 0.005), with fibrosis absence (P = 0.01) and protection for advanced fibrosis (P = 0.01). The TAA haplotype was protective for NASH (P = 0.002), and TGG haplotype was protective for MetS (P = 0.01).Conclusion: UCP3 gene variants were associated with protection against NASH and MetS, in addition to lower values of liver enzymes, lipid profile, BMI and, lesser fibrosis severity in the studied population.
  • article 2 Citação(ões) na Scopus
    AFP score and metroticket 2.0 perform similarly and could be used in a ""within-ALL"" clinical decision tool
    (2023) PINERO, Federico; COSTENTIN, Charlotte; DEGROOTE, Helena; NOTARPAOLO, Andrea; BOIN, Ilka FSF.; BOUDJEMA, Karim; BACCARO, Cinzia; CHAGAS, Aline; BACHELLIER, Philippe; ETTORRE, Giuseppe Maria; PONIACHIK, Jaime; MUSCARI, Fabrice; DIBENEDETTO, Fabrizio; DUQUE, Sergio Hoyos; SALAME, Ephrem; CILLO, Umberto; MARCIANO, Sebastian; VANLEMMENS, Claire; FAGIUOLI, Stefano; CARRILHO, Flair; CHERQUI, Daniel; BURRA, Patrizia; VLIERBERGHE, Hans Van; LAI, Quirino; SILVA, Marcelo; RUBINSTEIN, Fernando; DUVOUX, Christophe
    Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds.Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds.Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p <0.0001). At last tumor reassessment before LT, c statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs. 0.68; p = 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models (""within-ALL"") at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6).Conclusions: In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach.Impact and implications: Composite models were recently proposed for the selection of liver transplant (LT) candidates among individuals with hepatocellular carcinoma (HCC). We found that both the AFP score and Metroticket 2.0 predicted post-LT HCC recurrence and survival better than Milan criteria; the Metroticket 2.0 did not result in better reclassification for transplant selection compared to the AFP score, with predictive gaps and overlaps between the two models; patients who met low-risk thresholds for both models had the lowest 5-year recurrence rate. We propose prospectively testing the combination of both models, to further optimize the LT selection process for candidates with HCC.& COPY; 2022 The Authors.
  • article 0 Citação(ões) na Scopus
    Treatment Outcomes in Patients with Advanced Fibrolamellar Hepatocellular Carcinoma Under Systemic Treatment: Analysis of Clinical Characteristics, Management, and Radiomics
    (2023) FONSECA, Leonardo Da; YAMAMOTO, Victor Junji; CUNHA, Mateus Trinconi; TORRE, Giovanna Sawaya; ARAUJO, Raphael L. C.; FONSECA, Gilton Marques; CHEN, Andre Tsin Chih; CHAGAS, Aline Lopes; HERMAN, Paulo; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair Jose
    Purpose: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare primary liver malignancy often diagnosed at advanced stages. While there are limited data on the efficacy of specific agents, we aim to report outcomes of patients treated with systemic therapies and explore prognostic factors.Patients and Methods: Medical records of patients treated between 2010 and 2022 were reviewed. Treatments were defined after multidisciplinary assessment. Descriptive statistics were used for baseline demographics. Time-to-event outcomes were estimated using the Kaplan-Meier method, compared by log-rank and adjusted by a regression model. Radiomic features (including size, shape, and texture) of the primary lesion were extracted and dimensionality reduced. An unsupervised Gaussian Mixture Model (GMM) clustering was performed, and survival was compared between clusters.Results: We identified 23 patients: 12 males, with a median age of 23.6 years. At diagnosis, 82.6% had metastases, most frequently to the lungs (39.1%), lymph nodes (39.1%), and peritoneum (21.7%). Patients received a median of three lines (1-8) of treatment, including different regimens. Sorafenib (39.1%), capecitabine (30.4%), and capecitabine/interferon (13%) were the most used first-line regimens. The median time-to-failure was 3.8 months (95% CI: 3.2-8.7). Capecitabine + interferon (42.1%) and platinum combinations (39.1%) were the most used second-line regimens, with a time-to-failure of 3.5 months (95% CI: 1.5-11.6). Median overall survival was 26.7 months (95% CI: 15.1-40.4). A high baseline neutrophil-to-lymphocyte ratio (NLR) was associated with worse survival (p=0.02). Radiomic features identified three clusters, with one cluster (n=6) having better survival (40.4 vs 22.6 months, p=0.039). Tumor sphericity in the arterial phase was the most relevant characteristic associated with a better prognosis (accuracy=0.93).Conclusion: FLHCC has unique features compared to conventional HCC, including young onset, gender balance, and absence of hepatopathy. Systemic therapies can provide encouraging survival, but lack of uniformity precludes defining a preferable regimen. Radiomics and NLR were suggested to correlate with prognosis and warrant further validation.
  • article 1 Citação(ões) na Scopus
    P53 and VEGF are promising biomarkers for sorafenib efficacy in an experimental model of NASH-related HCC
    (2023) NASSAR-REIS, Joao Pedro; UMETA, Pedro Fukui; STEFANO, Jose Tadeu; LONGATTO-FILHO, Adhemar; CARRILHO, Flair Jose; ALVES, Venancio Avancini Ferreira; COGLIATI, Bruno; OLIVEIRA, Claudia P.
    The efficacy of systemic therapy for hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is poorly understood. In this study we evaluated the effects of sorafenib based on the expression of molecular markers related to major hepatocarcinogenesis pathways and angiogenesis in a NASH-related HCC model. Forty male rats were submitted to NASH-HCC induction through the combination of a high-fat and choline deficient diet and diethylnitrosamine (100 mg/L) administration in the drinking water for 13 and 16 weeks. After the induction period, the rats received daily gavage administration of saline solution (control) or Sorafenib (5 mg/kg/day) for 3 weeks. Thereafter, the animals were euthanized and samples from liver nodules were collected for histopathological analysis and immunohistochemical assessment of HEP-PAR-1, glutamine-synthetase, VEGF, survivin, & beta;-catenin and p53. A semi-quantitative score was used for VEGF, survivin and & beta;-catenin analysis. For p53, the percentage of positive cells was determined. Results were processed by Wilcoxon's test or Student's t-test. Both protocols efficiently induced HCC, most of them being moderately to poorly differentiated. Sorafenib-treated animals showed a decreased expression of VEGF and p53 in HCCs generated at 13 weeks when compared to control animals (p = 0.03; p = 0.04, respectively). No significant difference in & beta;-catenin and survivin were observed. There was a significant decrease in VEGF and p53 expression when comparing the two control groups (13 vs. 16 weeks, p < 0.01). p53 and VEGF are promising biomarkers for assessment of efficacy of Sorafenib, whereas survivin and & beta;-catenin were not found useful. Decreased immunohistochemical expression of p53 and VEGF in the 16 week control group may indicate a different metabolic status of HCC.
  • article 0 Citação(ões) na Scopus
    Impact of radiotherapy on adverse events of self-expanding metallic stents in patients with esophageal cancer
    (2023) MACHADO, Andressa A.; MARTINS, Bruno C.; JOSINO, Iatagan R.; CHEN, Andre T. C.; HONG, Carlos B. C.; SANTOS, Alisson L. D. R.; LIMA, Gustavo R. A.; CORDERO, Martin A. C.; V, Adriana Safatle-Ribeiro; PENNACCHI, Caterina; GUSMON, Carla C.; PAULO, Gustavo A.; LENZ, Luciano; LIMA, Marcelo S.; BABA, Elisa R.; KAWAGUTI, Fabio S.; UEMURA, Ricardo S.; SALLUM, Rubens A. A.; JR, Ulysses Ribeiro; MALUF-FILHO, Fauze
    Self-expanding metallic stents (SEMS) are considered the treatment of choice for the palliation of dysphagia and fistulas in inoperable esophageal neoplasms. However, the safety of SEMSs in patients who received or who will be submitted to radiotherapy (RT) is uncertain. The study aimed to evaluate the impact of RT on adverse events (AEs) in patients with esophageal cancer with SEMSs. This is a retrospective study conducted at a tertiary cancer hospital from 2009 to 2018. We collected information regarding RT, the histological type of the tumor, the model of SEMSs and AEs after stent placement. Three hundred twenty-three patients with malignant stenosis or fistula were treated with SEMSs. The predominant histological type was squamous cell carcinoma (79.6%). A total of 282 partially covered and 41 fully covered SEMSs were inserted. Of the 323 patients, 182 did not received RT, 118 received RT before SEMS placement and 23 after. Comparing the group that received RT before stent insertion with the group that did not, the first one presented a higher frequency of severe pain (9/118 7.6% vs. 3/182 1.6%; P = 0.02). The group treated with RT after stent placement had a higher risk of global AEs (13/23 56.5% vs. 63/182 34.6%; P = 0.019), ingrowth/overgrowth (6/23 26.1% vs. 21/182 11.5%; P = 0.045) and gastroesophageal reflux (2/23 8.7% vs. 2/182 1.1%; P = 0.034). Treatment with RT before stent placement in patients with inoperable esophageal neoplasm prolongs survival and is associated with an increased risk of severe chest pain. Treatment with RT of patients with an esophageal stent increases the frequency of minor, not life-threatening AEs.