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1.
Ann Hepatol ; 29(3): 101489, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38403068

RESUMO

INTRODUCTION AND OBJECTIVES: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. PATIENTS AND METHODS: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. RESULTS: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). CONCLUSIONS: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Recidiva , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Vacinas contra COVID-19/efeitos adversos , Estudos Retrospectivos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Estudos Prospectivos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , SARS-CoV-2 , Idoso , Adulto , Imunização Secundária , Fatores de Risco , Transplante de Fígado , Imunossupressores/efeitos adversos
2.
J Behav Med ; 47(1): 111-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37572138

RESUMO

BACKGROUND: Affective response to exercise (i.e., how individuals feel during- and post-exercise) as well as post-behavioral evaluations of affective experiences with exercise (i.e., reflecting on the experience after engaging in exercise) may be important determinants of regular exercise. PURPOSE: We compared post-exercise affective response and post-behavioral evaluations of exercise between a physically active and underactive group. Physically active (n = 32) and underactive (n = 25) participants completed a 10-minute treadmill bout of vigorous exercise and reported affective valence, positive activated affect, negative activated affect, calmness, fatigue and relief at various points during and/or after the bout. RESULTS: As expected, both groups reported an improvement in affective valence immediately post-exercise (ps < 0.001). This improvement in affective valence was associated with a concurrent decrease in negative affect (ps < 0.05) for the physically underactive group and was only associated with a concurrent increase in positive affect (ps < 0.02) for the active group. There were significant differences between physically active and underactive groups in pre-post exercise changes in positive activated affect (ps < 0.005). The underactive group reported greater relief than the active group at all-post exercise time-points (ps < 0.05). CONCLUSIONS:  These findings have implications for understanding post-exercise affective response and post-behavioral evaluations of exercise and for interventions directed at influencing the post-exercise affective response and behavioral evaluations of exercise in physically underactive individuals.


Assuntos
Afeto , Exercício Físico , Humanos , Afeto/fisiologia , Exercício Físico/psicologia , Emoções , Fadiga/psicologia , Teste de Esforço
3.
Gastroenterol Hepatol ; 46(4): 288-296, 2023 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36115630

RESUMO

BACKGROUND: Bacterial infections remain one of the main complications in cirrhosis and worsen patients' prognosis and quality of life. An increase in multidrug resistant microorganism (MDRM) infections among patients with cirrhosis, together with infection-related mortality rates, have been reported in recent years. Therefore, adaptation of the initial empiric antibiotic approach to different factors, particularly the local epidemiology of MDRM infections, has been recommended. We aim to describe the main features, outcomes and risk factors of MDRM infections in patients with cirrhosis. METHODS: Prospective registry of all episodes of in-hospital infections occurring among cirrhotic patients admitted within a 2-year period at a single center. Clinical and microbiological data were collected at the time of infection diagnosis, and the in-hospital mortality rate of the infectious episode was registered. RESULTS: A total of 139 infectious episodes were included. The disease-causing microorganism was identified in 90 episodes (65%), of which 31 (22%) were caused by MDRM. The only two factors independently associated with MDRM infections were rectal colonization by MDRM and a nosocomial or healthcare-associated source. The infection-related mortality rate was 18.7%. MDRM infection and a past history of hepatic encephalopathy were independently associated with in-hospital mortality. CONCLUSIONS: Almost one fourth of bacterial infections occurring in admitted cirrhotic patients were due to MDRM. Rectal colonization was the most important risk factor for MDRM infections in decompensated cirrhosis. Screening for MDRM rectal colonization in patients admitted for decompensated cirrhosis should be assessed as a tool to improve local empiric antibiotic strategies.


Assuntos
Infecções Bacterianas , Qualidade de Vida , Humanos , Estudos Prospectivos , Incidência , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/complicações , Fatores de Risco , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Antibacterianos/uso terapêutico
4.
Liver Int ; 42(5): 1109-1120, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35220659

RESUMO

BACKGROUND & AIMS: Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort. METHODS: This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end-stage liver disease (MELD). We evaluated bacterial infections, liver-related complications, mortality and liver function tests after 90 days. RESULTS: Twenty-one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute-on-chronic liver failure (ACLF) linked to infections within the treatment group. Liver-related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment. CONCLUSIONS: Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.


Assuntos
Insuficiência Hepática Crônica Agudizada , Infecções Bacterianas , Hepatite Alcoólica , Insuficiência Hepática Crônica Agudizada/complicações , Infecções Bacterianas/complicações , Infecções Bacterianas/tratamento farmacológico , Hepatite Alcoólica/complicações , Hepatite Alcoólica/tratamento farmacológico , Humanos , Projetos Piloto , Rifaximina/uso terapêutico
5.
Liver Int ; 42(8): 1891-1901, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35608939

RESUMO

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.


Assuntos
COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , COVID-19/complicações , Teste para COVID-19 , Estudos de Coortes , Estudos Transversais , Humanos , Estudos Retrospectivos , SARS-CoV-2
6.
Am J Gastroenterol ; 116(11): 2250-2257, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34158466

RESUMO

INTRODUCTION: Obeticholic acid (OCA) and fibrates therapy results in biochemical improvement in placebo-controlled trials in patients with primary biliary cholangitis and insufficient response to ursodeoxycholic acid. There is scarce information outside of clinical trials. Therefore, we have assessed the effectiveness and adverse events of these treatments. METHODS: Data from patients included in the ColHai registry treated with OCA, fibrates, or both were recorded during a year, as well as adverse events and treatment discontinuation. RESULTS: Eighty-six patients were treated with OCA, 250 with fibrates (81% bezafibrate; 19% fenofibrate), and 15 with OCA plus fibrates. OCA group had baseline significantly higher alkaline phosphatase (ALP) (P = 0.01) and lower platelets (P = 0.03) than fibrates. Both treatments significantly decreased ALP, gamma-glutamyl transferase (GGT), and transaminases and improved Globe score. Albumin and immunoglobulin type M improved in the fibrates group. ALP decrease was higher under fibrates, whereas alanine aminotransferase decline was higher under OCA. Although baseline transaminases and GGT were higher in patients with OCA plus fibrates, significant ALP, GGT, alanine aminotransferase, and Globe score improvement were observed during triple therapy. Adverse events were reported in 14.7% of patients (21.3% OCA; 17.6% fenofibrate; 10.7% bezafibrate), mainly pruritus (10.1% with OCA). Discontinuation was more frequent in fenofibrate treatment mainly because of intolerance or adverse events. DISCUSSION: Second-line therapy with OCA or fibrates improves hepatic biochemistry and the GLOBE score in primary biliary cholangitis patients with suboptimal response to ursodeoxycholic acid. Simultaneous treatment with OCA and fibrates improved ALP as well.


Assuntos
Bezafibrato/uso terapêutico , Ácido Quenodesoxicólico/análogos & derivados , Fenofibrato/uso terapêutico , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Quenodesoxicólico/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
7.
Eat Weight Disord ; 26(6): 1957-1962, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33070265

RESUMO

PURPOSE: Body dissatisfaction is ubiquitous in our society and leads to eating disorders. Longitudinal research suggests that higher body dissatisfaction predicts higher negative affect and unhealthy weight control behaviors over time. However, no study has assessed how body dissatisfaction impacts affect and weight control behaviors in the moment. In the current study, we examined the momentary relationships between body dissatisfaction, affect and weight control behaviors using ecological momentary assessment. METHODS: Female college students (N = 67) completed measures of state body dissatisfaction, affect, and weight control behaviors across fourteen days using ecological momentary assessment. RESULTS: Greater body dissatisfaction significantly predicted lower subsequent positive affect and higher subsequent negative affect, but positive and negative affect did not predict subsequent body dissatisfaction. Daily average body dissatisfaction was not significantly associated with daily engagement in either healthy or unhealthy weight control behaviors. CONCLUSION: Short-term negative effects of body dissatisfaction on affect were apparent. Targeting body dissatisfaction may be important for improving affect. LEVEL OF EVIDENCE: Level IV, multiple time series without intervention.


Assuntos
Insatisfação Corporal , Transtornos da Alimentação e da Ingestão de Alimentos , Avaliação Momentânea Ecológica , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Estudantes
8.
J Hepatol ; 73(2): 328-341, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32240714

RESUMO

BACKGROUND & AIMS: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB. METHODS: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies. RESULTS: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth. CONCLUSIONS: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. LAY SUMMARY: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer.


Assuntos
Colina Quinase , Hepatoblastoma , Neoplasias Hepáticas , beta Catenina/genética , Biomarcadores Tumorais/análise , Proteínas de Ligação ao Cálcio/genética , Colina Quinase/antagonistas & inibidores , Colina Quinase/metabolismo , Metilação de DNA , Descoberta de Drogas/métodos , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Hepatoblastoma/genética , Hepatoblastoma/metabolismo , Hepatoblastoma/mortalidade , Hepatoblastoma/patologia , Ensaios de Triagem em Larga Escala , Humanos , Lactente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Prognóstico , Medição de Risco/métodos
9.
Liver Int ; 40(6): 1467-1476, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32170821

RESUMO

BACKGROUND & AIMS: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. METHODS: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. RESULTS: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. CONCLUSIONS: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Europa (Continente) , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Diálise Renal , Sorafenibe/uso terapêutico , Resultado do Tratamento
10.
Int J Eat Disord ; 53(6): 834-851, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32100320

RESUMO

OBJECTIVE: Mindfulness is implicated in eating disorder (ED) psychopathology. However, this literature has not been synthesized to date. The current meta-analysis examined the associations between mindfulness and ED psychopathology. METHODS: A total of 74 independent samples (effects = 576) were included. We used a multilevel random-effects model to estimate summary study-level effect sizes, and multilevel mixed-effects models to examine moderator effects. RESULTS: Mindfulness was negatively associated with ED psychopathology (r = -.25, p < .001), both concurrently (r = -.25, p < .001) and prospectively (rs = -.22 to -.24, ps < .001). Associations were strongest for binge eating, emotional/external eating, and body dissatisfaction as well as the acting with awareness and nonjudging facets. DISCUSSION: Mindfulness may be an important process in ED psychopathology. Future research should prospectively and experimentally examine the relation between mindfulness and ED psychopathology.


OBJETIVO: La atención plena (mindfulness) está implicada en la psicopatología de los trastornos de la conducta alimentaria (TCA). Sin embargo, esta literatura no ha sido sintetizada a la fecha. El presente meta-análisis examinó las asociaciones entre la atención plena y la psicopatología de los TCA. MÉTODOS: Se incluyeron un total de 74 muestras independientes (efectos = 576). Utilizamos un modelo de efectos aleatorios multinivel para estimar la síntesis de los tamaños de efecto por nivel de estudio, y los modelos de efecto mixto multinivel para examinar los efectos moderadores. RESULTADOS: La atención plena fue asociada negativamente con la psicopatología de TCA (r = −.25, p < .001), tanto concurrentemente (r = −.25, p < .001) como prospectivamente (rs = −.22-−.24, ps < .001). Las asociaciones fueron más fuertes para trastorno por atracón, alimentación emocional/externa, e insatisfacción corporal, así como también el actuar con conciencia y sin juzgar las facetas. DISCUSIÓN: La atención plena (mindfulness) puede ser un proceso importante en la psicopatología de los TCA.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Atenção Plena/métodos , Psicopatologia/métodos , Adulto , Feminino , Humanos , Masculino
11.
Int J Eat Disord ; 53(4): 625-630, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32112594

RESUMO

OBJECTIVE: Eating disorders (EDs) are characterized by significant anxiety during mealtime that contributes to food avoidance and weight loss. Individuals with EDs commonly use avoidance coping (e.g., distraction) to tolerate meals and comply with meal plans. Although this strategy may be effective short term, a large body of anxiety literature suggests that avoidance can lead to worsening of psychological symptoms long term. METHOD: The current study (N = 66 individuals diagnosed with ED) used ecological momentary assessment (EMA) to examine the short-term and long-term associations of avoidance coping on ED symptoms. RESULTS: Distraction during meals predicted a reduction in anxiety in the short term, and both distraction and avoidance of emotions predicted increases in excessive exercise in the short term. Distraction and avoidance of emotions predicted increases in bulimic symptoms 1 month after completion of EMA. DISCUSSION: These results are consistent with prior literature on avoidance and suggest that avoidance coping during meals may contribute to the increase of ED behaviors in the long term. Coping strategies that encourage approach and tolerance of difficult thoughts and emotions (e.g., acceptance-based strategies) rather that avoidance coping may promote longer-term symptom reduction.


Assuntos
Adaptação Psicológica/fisiologia , Ansiedade/psicologia , Emoções/fisiologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Refeições/psicologia , Feminino , Humanos , Masculino
12.
J Hepatol ; 70(5): 874-884, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30684506

RESUMO

BACKGROUND & AIMS: Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC. METHODS: This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years. RESULTS: A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96-4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55-5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased. CONCLUSION: These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation. LAY SUMMARY: In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Hepatite C/tratamento farmacológico , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Hepatite C/complicações , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resposta Viral Sustentada , Fatores de Tempo
13.
Hepatology ; 67(2): 612-622, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28898447

RESUMO

The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic reactions have shown to have a positive outcome. In addition, sorafenib is described as an antiangiogenic drug, but it also acts on immunological cells. Thus, the goal of this study was to assess the complete response rate in a retrospective cohort of HCC patients treated with sorafenib and to describe the profile of the patients who achieve complete response for identifying factors related to this event and their connection with the immunological profile of sorafenib. Ten Spanish centers submitted cases of complete response under sorafenib. The baseline characteristics, development of early dermatologic reactions, and cause of treatment discontinuation were annotated. Radiological images taken before starting sorafenib, at first control, after starting sorafenib, at the time of complete response, and at least 1 month after treatment were centrally reviewed. Of the 1119 patients studied, 20 had been classified as complete responders by the centers, but eight of these patients were excluded after central review. Ten patients had complete disappearance of all tumor sites, and two had just a small residual fibrotic scar. Thus, 12 patients were classified as complete responders (58% HCV, median age 59.7 years, 83.4% Child-Pugh class A, Eastern Cooperative Oncology Group performance status 0 91.7%, and Barcelona Clinic Liver Cancer stage C 83.3%). The median overall survival and treatment duration were 85.8 and 40.1 months, respectively. All but one patient developed early dermatologic reactions, and seven patients discontinued sorafenib after achieving complete response due to adverse events, patient decision, or liver decompensation. Conclusion: Complete response affects 1% of patients with HCC who are treated with sorafenib. The association of complete response with early dermatologic reactions supports the role of a specific immune/inflammatory patient profile in the improved response to sorafenib. (Hepatology 2018;67:612-622).


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Pele/efeitos dos fármacos , Sorafenibe/uso terapêutico , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sorafenibe/efeitos adversos , alfa-Fetoproteínas/análise
14.
FASEB J ; 32(7): 3878-3891, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29465313

RESUMO

CD5-like (CD5L) is a soluble scavenger cysteine-rich protein that modulates inflammatory responses. We studied the involvement of CD5L in liver cancer. Immunohistochemistry (IHC) of CD5L in 60 hepatocellular carcinomas and 34 adjacent nontumor livers, showed that CD5L staining was higher in tumor than in nontumor tissue (Mann-Whitney test; P = 0.0039). High CD5L correlated with elevated proliferation (Ki67, linear regression; P < 0.0001) and lower patient event-free survival (log-rank; P = 0.0185). Accordingly, CD5L expression was detected in the liver cancer cell lines Huh7, HepG2, and SNU-398. In vitro technologies using these cell lines, including small interfering RNA (siRNA) and cDNA transfection, showed that CD5L promoted colony formation and cell proliferation and protected against cisplatin-induced apoptosis. To find a molecular explanation for these roles, novel CD5L-interacting protein ligands in liver cancer cells were identified by immunoprecipitation followed by mass spectrometry. Among these, the molecular chaperone of the unfolded protein response (UPR), heat shock protein (HSP)-A5, was selected for validation. The interaction was confirmed by confocal microscopy in the Huh7 and HepG2 cell lines. Furthermore, functional experiments revealed that CD5L activates the UPR and autophagy mechanisms in Huh7 cells, thereby providing a novel molecular link between the UPR and autophagy in liver cancer.-Aran, G., Sanjurjo, L., Bárcena, C., Simon-Coma, M., Téllez, É., Vázquez-Vitali, M., Garrido, M., Guerra, L., Díaz, E., Ojanguren, I., Elortza, F., Planas, R., Sala, M., Armengol, C., Sarrias, M.-R. CD5L is upregulated in hepatocellular carcinoma and promotes liver cancer cell proliferation and antiapoptotic responses by binding to HSPA5 (GRP78).


Assuntos
Apoptose , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Neoplasias Hepáticas/metabolismo , Receptores Depuradores Classe B/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Chaperona BiP do Retículo Endoplasmático , Feminino , Proteínas de Choque Térmico/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Receptores Depuradores , Receptores Depuradores Classe B/genética , Resposta a Proteínas não Dobradas , Regulação para Cima
15.
Eur Eat Disord Rev ; 27(3): 295-305, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30467917

RESUMO

Mindfulness-based treatments for eating disorders could be improved by understanding how facets of mindfulness predict eating disorder symptoms over time. We examined whether facets of mindfulness predict eating disorder symptoms over time and vice versa. Individuals with an eating disorder diagnosis (N = 124; 87.9% diagnosed with anorexia nervosa) and an undergraduate sample (N = 290) completed measures of mindfulness at baseline. The clinical sample also completed these measures 1 month later. Individuals in the clinical sample had lower acting with awareness and higher observing than individuals in the undergraduate sample (ps < 0.002). In the clinical sample, higher body dissatisfaction prospectively predicted lower acting with awareness (p = 0.02). Lower acting with awareness prospectively predicted higher drive for thinness (p < 0.01) and bulimic symptoms (p < 0.01). Acting with awareness shows potential as a process that can be altered to effect positive outcomes on drive for thinness and bulimic symptoms.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Atenção Plena , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Eat Weight Disord ; 24(6): 1079-1088, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30847689

RESUMO

BACKGROUND: Eating disorders are characterized by high levels of anxiety, especially while eating. However, little is known about anxiety experienced during meals and specifically what other variables may impact such anxiety. OBJECTIVE: We sought to further quantify and understand the relationship between food anxiety, eating disorders, and related correlates (e.g., comorbid diagnoses, personality). METHODS: In the current study [N = 42 participants diagnosed with an eating disorder (n = 36 participants with anorexia nervosa)], we quantified anxiety before, during, and after a meal using data from a food exposure session in a partial hospital eating disorder center. We examined diagnostic, personality, and clinical factors as correlates of food anxiety. RESULTS: Participants were more likely to experience higher food anxiety if they had a current diagnosis of major depression, obsessive-compulsive disorder, or post-traumatic stress disorder (PTSD). Concern over mistakes was the strongest and most consistent correlate of food anxiety regardless of time during the meal that anxiety was assessed. Other significant correlates were fear of positive evaluation, social appearance anxiety, BMI, and trust. CONCLUSIONS: These findings show how diagnoses, perfectionism (concern over mistakes), and other correlates relate to anxiety during meals. Food exposure interventions may benefit from personalizations that address these factors. LEVEL OF EVIDENCE: IV Evidence from a randomized control trial, but from the first session before effects of the design would be present.


Assuntos
Anorexia Nervosa/psicologia , Ansiedade/psicologia , Bulimia Nervosa/psicologia , Alimentos , Refeições/psicologia , Personalidade , Anorexia Nervosa/terapia , Bulimia Nervosa/terapia , Hospital Dia , Transtorno Depressivo Maior/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Humanos , Terapia Implosiva , Transtorno Obsessivo-Compulsivo/psicologia , Perfeccionismo , Transtornos de Estresse Pós-Traumáticos/psicologia
17.
Appetite ; 129: 252-261, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29958864

RESUMO

OBJECTIVE: Outcome variables gauging the frequency of specific disordered eating behaviors (e.g., binge eating, vomiting) are common in the study of eating and health behaviors. The nature of such data presents several analytical challenges, which may be best addressed through the application of underutilized statistical approaches. While zero-sensitive models are well-supported by methodologists, application of these models has yet to gain traction among a widespread audience of researchers who study eating-related behaviors. The current study examined several approaches to predicting count-based behaviors, including zero-sensitive (i.e., zero-inflated and hurdle) regression models. METHOD: Exploration of alternative models to predict eating-related behaviors occurred in two parts. In Part 1, participants (N = 524; 54% female) completed the Eating Disorder Examination-Questionnaire and Daily Stress Inventory. We considered the theoretical basis and practical utility of several alternative approaches for predicting the frequency of binge eating and compensatory behaviors, including ordinary least squares (OLS), logistic, Poisson, negative binomial, and zero-sensitive models. In Part 2, we completed Monte Carlo simulations comparing negative binomial, zero-inflated negative binomial, and negative binomial hurdle models to further explore when these models are most useful. RESULTS: Traditional OLS regression models were generally a poor fit for the data structure. Zero-sensitive models, which are not limited to traditional distribution assumptions, were preferable for predicting count-based outcomes. In the data presented, zero-sensitive models were useful in modeling behaviors that were relatively rare (laxative use and vomiting, 9.7% endorsed) along with those that were somewhat common (binge eating, 33.4% endorsed; driven exercise, 40.7% endorsed). Simulations indicated missing data, sample size, and the number of zeros may impact model fit. DISCUSSION: Zero-sensitive approaches hold promise for answering key questions about the presence and frequency of common eating-related behaviors and improving the specificity of relevant statistical models. The current manuscript provides practical guidance to aid the use of these models when studying eating-related behaviors.


Assuntos
Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Modelos Psicológicos , Modelos Estatísticos , Adolescente , Feminino , Humanos , Masculino , Método de Monte Carlo , Análise de Regressão , Inquéritos e Questionários
18.
Eat Weight Disord ; 23(6): 731-737, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30288725

RESUMO

INTRODUCTION: Anorexia nervosa (AN) is a serious psychiatric disorder that is difficult to treat and often follows a protracted course. A number of theoretical models have been proposed for the etiology and maintenance of AN. Two domains that have received substantial attention in the literature on AN are affect and reward/punishment processes. However, despite an overlap in the nature and implications of these processes, studies of AN addressing these constructs have typically investigated them independently. PURPOSE: The purpose of this narrative review is to integrate the literature on the role of affect, reward, and punishment in AN. METHOD: We provide a focused narrative overview of the literature relating to the affect, reward, and punishment in AN via a synthesis of recent reviews and meta-analyses. RESULTS: We first describe several prominent affect and reward/punishment-based conceptualizations of AN, followed by a brief overview of the existing empirical literature in these domains. CONCLUSION: We provide a critical discussion of the disparate nature of these literatures in AN, including associated limitations. We then conclude with an extensive discussion of directions for future research that integrate the study of affect and reward/punishment processes in AN. LEVEL OF EVIDENCE: Level V, narrative review.


Assuntos
Afeto/fisiologia , Modelos Psicológicos , Punição , Recompensa , Anorexia Nervosa/psicologia , Humanos
19.
Int J Eat Disord ; 50(12): 1413-1420, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29098699

RESUMO

OBJECTIVE: Stress is associated with the maintenance of eating disorders and exercise behaviors. However, it is unclear how stress is associated with exercise and vice-versa among individuals with higher levels of eating disorder symptoms in daily life. The current study tested the moderating effect of eating disorder symptoms on the relationships between (1) daily stress and later exercise behavior and (2) daily exercise behavior and later stress. METHOD: Female college students [N = 129, mean age = 19.19 (SD = 1.40)] completed the Eating Disorder Inventory-2. Participants then completed measures of stress and exercise four times daily across seven days using an automated telephone ecological momentary assessment system. Data were analyzed using multilevel models. RESULTS: Drive for thinness, bulimic symptoms, and body dissatisfaction significantly moderated the relationship between daily stress and later exercise (ps = .01-.05), such that higher daily stress predicted higher later exercise only in individuals who were low (but not average or high) in drive for thinness, bulimic symptoms, and body dissatisfaction symptoms. DISCUSSION: Stress is associated with exercise differentially depending on individuals' eating disorder symptoms. Our findings suggest that only individuals with lower levels of eating disorder symptoms exercise when stressed.


Assuntos
Avaliação Momentânea Ecológica/estatística & dados numéricos , Exercício Físico/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Estresse Fisiológico/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
20.
J Women Aging ; 29(1): 3-14, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27399268

RESUMO

We conducted a qualitative study of 1,849 women over age 50 to capture the thoughts, feelings, and attitudes that women at middle age have about their bodies and the experience of aging. Via an open-ended question online survey, four primary themes emerged: (a) the physical and psychological experience of aging; (b) the injustices, inequities, and challenges of aging; (c) the importance of self-care; and (d) a plea for recognition of the need to maintain a contributory role in society. Results highlight the complexities of women's psychological and physical aspects of aging and point toward important topics worthy of further study in this growing population.


Assuntos
Envelhecimento/psicologia , Atitude Frente a Saúde , Imagem Corporal/psicologia , Identidade de Gênero , Feminino , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa , Saúde da Mulher
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