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There is sparse literature on the development of malignancy in remnant gastric stomach after bariatric Roux-en-Y gastric bypass surgery. We report a case of overt upper gastrointestinal bleeding from malignant adenocarcinoma in the remnant stomach presenting several years after bariatric Roux-En-Y gastric bypass surgery. The mass in the remnant stomach was surgically resected, and the patient was subsequently diagnosed with Lynch syndrome on genetic analysis.
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BACKGROUND: Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss. AIM: To explore the relationship between BMI and survival in patients with cirrhosis and HCC. METHODS: This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers. Patient and tumor characteristics were extracted manually from medical records of each institutions' cancer registries. Patients were stratified according to BMI classes: < 25 kg/m2 (lean), 25-29.9 kg/m2 (overweight), and > 30 kg/m2 (obese). Patient and tumor characteristics were compared according to BMI classification. We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria. A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC. RESULTS: A total of 2548 patients with HCC were included in the analysis of which 11.2% (n = 286) were classified as non-cirrhotic. The three main BMI categories: Lean (n = 754), overweight (n = 861), and obese (n = 933) represented 29.6%, 33.8%, and 36.6% of the total population overall. Within each BMI class, the non-cirrhotic patients accounted for 15% (n = 100), 12% (n = 94), and 11% (n = 92), respectively. Underweight patients with a BMI < 18.5 kg/m2 (n = 52) were included in the lean cohort. Of the obese cohort, 42% (n = 396) had a BMI ≥ 35 kg/m2. Out of 2262 patients with cirrhosis and HCC, 654 (29%) were lean, 767 (34%) were overweight, and 841 (37%) were obese. The three BMI classes did not differ by age, MELD, or Child-Pugh class. Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients (71%, 62%, 49%, P < 0.001). Lean patients had significantly larger tumors compared to the other two BMI classes (5.1 vs 4.2 vs 4.2 cm, P < 0.001), were more likely outside Milan (56% vs 48% vs 47%, P < 0.001), and less likely to undergo transplantation (9% vs 18% vs 18%, P < 0.001). While both tumor size (P < 0.0001) and elevated alpha fetoprotein (P < 0.0001) were associated with worse survival by regression analysis, lean BMI was not (P = 0.36). CONCLUSION: Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria, reflecting cancer related cachexia from delayed diagnosis. Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit, but not overweight or obese BMI classifications.
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INTRODUCTION: Beyond oral contraceptives (OCs), metabolic factors have been suggested to increase the risk of hepatocellular adenoma (HCA). The impact of risks remains poorly defined, particularly among men and those with adenomatosis. Thus, we aimed to examine HCA clinical and outcome characteristics through a large multicenter cohort. METHODS: HCA diagnosis was made based on a combination of clinical, radiologic, and histologic criteria. Patient and clinical data including follow-up imaging, complications, and interventions were collected between 2004 and 2018 from 3 large academic centers. RESULTS: Among 187 patients (163 female and 24 male) with HCA, 75 had solitary HCA, 58 had multiple HCAs, and 54 had adenomatosis. Over a median follow-up of 3.3 years (quartile 1: 1.2, quartile 3: 8.8), 34 patients (18%) had radiologic interventions, 41 (21%) had surgical resections, 10 (5%) developed tumoral hemorrhage, and 1 had malignant transformation. OC and corticosteroid use were present in 70% and 16%, respectively. Obesity (51%), type 2 diabetes (24%), hypertension (42%), and hypertriglyceridemia (21%) were also common. Metabolic comorbidities were more common in patients with large HCAs and adenomatosis. Compared with women, men had less hepatic steatosis (4% vs 27%), smaller HCAs (2.3 cm vs 4.4 cm), and more corticosteroid use (38% vs 11%) ( P < 0.05 for all). With OC cessation, 69% had a decrease in size of HCA, but 25% eventually required advanced interventions. DISCUSSION: In this large HCA cohort, obesity and metabolic comorbidities were important risk factors associated with large HCAs and adenomatosis. Long-term adverse outcomes were infrequent, 5% had tumor hemorrhage, and 1 patient exhibited malignant transformation.
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Adenoma de Células Hepáticas , Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Adenoma de Células Hepáticas/epidemiologia , Adenoma de Células Hepáticas/terapia , Corticosteroides , Transformação Celular Neoplásica , Feminino , Hemorragia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Fatores de RiscoRESUMO
Semaglutide has little hepatic metabolism and is deemed low risk for causing drug-induced liver injury (DILI). We present a case of DILI from the US DILI Network. The case involved a 51-year-old man with type 2 diabetes who presented with jaundice and acute-on-chronic kidney disease 6 months after starting oral semaglutide. His liver injury progressed to biliary cirrhosis, accompanied by nephritis that led to end-stage renal disease. Extensive evaluations including liver and kidney biopsies revealed no alternative etiologies. Cholestatic gene sequencing revealed heterozygosity for ABCC2 and DHCR7. He eventually underwent combined liver and kidney transplantation.
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BACKGROUND AND AIMS: Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation. APPROACH AND RESULTS: We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay. Serum levels of LP-Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z-index, calculated by the ratio of LP-Z to total apolipoprotein B-containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z-index was associated with 90-day mortality independent from the Model for End-Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z-index ≤ 0.6 and a decline of Z-index by ≥0.1 in 2 weeks predicted 90-day survival. RNA-sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP-Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP-Z particles caused direct toxicity to human hepatocytes in a concentration-dependent manner, supporting a pathogenic role of FC in LP-Z. CONCLUSIONS: Impaired lipoprotein metabolism in AH leads to the accumulation of LP-Z in the circulation, which is hepatotoxic from excessive FC. A Z-index ≤ 0.6 predicts 90-day survival independent from conventional biomarkers for disease prognostication.
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Doença Hepática Terminal , Hepatite Alcoólica , Apolipoproteínas B , Colesterol , Humanos , Lipoproteína(a) , Lipoproteínas , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction. METHODS: Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases. RESULTS: In the DAA era (2014-2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88-0.99, P = 0.019), without change in trends of other liver diseases-related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03-1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81-0.97, P = 0.009) along with similar trends for HCV-HCC-increase in noncirrhotic cases (OR 1.35, 95% CI 1.08-1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86-0.98, P = 0.012)-were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era. DISCUSSION: Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Idoso , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Hepatite B/complicações , Humanos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Alcohol-associated liver disease (ALD) and alcoholic hepatitis (AH) significantly impact the liver, an organ central to the lipid and lipoprotein metabolism. OBJECTIVE: To define changes in the lipid and lipoprotein profiles in subjects with alcoholic hepatitis (AH) versus heavy drinkers with normal liver function and to determine the association of the AH-mediated lipoprotein phenotype with AH severity and outcomes. METHODS: AH cases (n=196) and a heavy drinker control group (n=169) were identified in a multicenter, prospective cohort. The relationships between lipid panels and lipoprotein profiles among AH and heavy drinkers were interrogated using three common measurements: the conventional lipid panel, extended lipid panel by NMR, and NMR-based direct lipoprotein profiling. Predictive values for AH severity and mortality were determined using Harrell's C-Index. RESULTS: Lipid and lipoprotein profiles were significantly different in AH compared to heavy drinkers. Among them, high density lipoprotein (HDL) particle concentration exhibited the most significant reduction in AH compared to heavy drinkers (5.3 ± 3.4 vs 22.3 ± 5.4 µmol/L, p < 0.001). Within AH patients, HDL particle concentration was inversely associated with Maddrey's Discriminant Function (DF) (p < 0.001), and independently associated with mortality at both 90 and 365 days even after adjustment for DF (p = 0.02, p = 0.05 respectively). HDL particle concentration less than 3.5 µmol/L and total cholesterol ≤ 96 mg/dL identified AH patients with higher 90-day mortality. CONCLUSION: Lipid and lipoprotein profiles are profoundly altered in AH and can help in prognosticating disease severity and mortality.
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Alcoolismo/sangue , Hepatite Alcoólica/sangue , Lipídeos/sangue , Lipoproteínas HDL/sangue , Lipoproteínas/sangue , Adulto , Alcoolismo/diagnóstico , Alcoolismo/mortalidade , Colesterol/sangue , Diagnóstico Diferencial , Feminino , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/mortalidade , Humanos , Estimativa de Kaplan-Meier , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND & AIMS: Patients with irritable bowel syndrome (IBS) may pursue complementary and alternative medicine (CAM). We conducted a comprehensive systematic review and meta-analysis examining efficacy of CAM vs. placebo or sham in adults with IBS. METHODS: Publication databases were searched for randomized controlled trials of CAM therapies (herbal therapy, dietary supplements, mind-body based, body-based, and energy-healing) in adults with IBS. Data were extracted to obtain pooled estimates of mean improvement in abdominal pain (standardized mean difference [SMD]) and relative risk (RR) of overall response using random effects models. Sensitivity and subgroup analyses along with quality assessments were completed. RESULTS: Among 2825 articles identified, 66 were included. Herbal therapy (SMD=0.47, 95% CI: 0.20 to 0.75, I2=82%) demonstrated significant benefit over placebo for abdominal pain (low confidence in estimates). Benefit with mind-body based therapy for abdominal pain was of borderline significance (SMD=0.29, 95% CI: -0.01 to 0.59, I2=78%). Herbal therapy (RR=1.57, 95% CI: 1.31 to 1.88, I2=77%), dietary supplements (RR=1.95, 95% CI: 1.02 to 3.73, I2=75%), and mind-body based therapy (RR=1.67, 95% CI: 1.13 to 2.49, I2=63%) showed benefit for overall response compared to placebo (low confidence in estimates). Body-based and energy healing therapies demonstrated no significant benefit over placebo or sham for abdominal pain or overall response. CONCLUSIONS: CAM therapies such as herbal or dietary supplements and mind-body based approaches may be beneficial for abdominal pain and overall response in IBS. However, overall quality of evidence is low. Rigorous, high quality clinical trials are warranted to investigate CAM in IBS.
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Terapias Complementares , Síndrome do Intestino Irritável , Dor Abdominal , Adulto , Humanos , Síndrome do Intestino Irritável/terapiaRESUMO
The prevalence and impact of hepatic steatosis among patients with autoimmune hepatitis (AIH) is not well described.We conducted a cross-sectional study to determine the prevalence of hepatic steatosis in AIH patients and examined its relationship with hepatic fibrosis using vibration controlled transient elastography. Liver stiffness measurement (LSM), controlled attenuation parameter (CAP), gender, current age, and body mass index (BMI) were collected from 277 AIH patients. Hepatic steatosis was defined as CAP >263âdb/m.The study participants were mostly female (82%) with an average age of 49 years and BMI 29.7âkg/m. Mean LSM was 12.5 (standard deviation 13.5) kPa and CAP was 244 (standard deviation 63) db/m. The prevalence of coexisting steatosis was 33.2%, and steatosis did not correlate with LSM (râ=â0.05, Pâ=â.46). In this study, only gender (females with 31% lower LSM on average compared to males, Pâ=â.001) and BMI (each unit increase of BMI resulted in a 1.48% increase on average LSM, Pâ=â.01) correlated with LSM. Male gender had significant association with increased LSM, after controlling for age, BMI, and CAP (Pâ=â.001).This exploratory study using noninvasive vibration controlled transient elastography revealed hepatic steatosis is highly prevalent in patients with AIH but not associated with liver fibrosis.
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Técnicas de Imagem por Elasticidade , Fígado Gorduroso/diagnóstico , Hepatite Autoimune/complicações , Índice de Massa Corporal , Estudos Transversais , Fígado Gorduroso/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
BACKGROUND: We examined how extra-hepatic comorbidity burden impacts mortality in patients with cirrhosis referred for liver transplantation (LT). METHODS: Adults with cirrhosis evaluated for their first LT in 2012 were followed through their clinical course with last follow up in 2019. Extra-hepatic comorbidity burden was measured using the Charlson Comorbidity Index (CCI). The endpoints were 90-day transplant free survival (Cox-Proportional Hazard regression), and overall mortality (competing risk analysis). RESULTS: The study included 340 patients, mean age 56 ± 11, 63% male and MELD-Na 17.2 ± 6.6. The CCI was 0 (no comorbidities) in 44%, 1-2 in 44% and > 2 (highest decile) in 12%, with no differences based on gender but higher CCI in patients with fatty and cryptogenic liver disease. Thirty-three (10%) of 332 patients not receiving LT within 90 days died. Beyond MELD-Na, the CCI was independently associated with 90-day mortality (hazard ratio (HR), 1.32 (95% confidence interval (CI) 1.02-1.72). Ninety-day mortality was specifically increased with higher CCI category and MELD ≥18 (12% (CCI = 0), 22% (CCI = 1-2) and 33% (CCI > 2), (p = 0.002)) but not MELD-Na ≤17. At last follow-up, 69 patients were alive, 100 underwent LT and 171 died without LT. CCI was associated with increased overall mortality in the competing risk analysis (Sub-HR 1.24, 95%CI 1.1-1.4). CONCLUSIONS: Extra-hepatic comorbidity burden significantly impacts short-term mortality in patients with cirrhosis and high MELD-Na. This has implications in determining urgency of LT and mortality models in cirrhosis and LT waitlisting, especially with an ageing population with increasing prevalence of fatty liver disease.
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Hepatopatias , Transplante de Fígado , Adulto , Idoso , Comorbidade , Feminino , Humanos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , SódioRESUMO
BACKGROUND AND AIMS: Utilization and safety of cannabidiol (CBD) in patients with autoimmune hepatitis (AIH) are currently unknown. We aimed to identify the frequency of CBD use, impact on symptoms, and safety profile. METHODS: An invitation to complete a CBD-specific questionnaire was posted every other day to well-established autoimmune hepatitis Facebook communities (combined membership of 2600 individuals) during a 10-day study period. Age ≥ 18 years and an AIH diagnosis by a physician were the eligibility criteria for participation in the survey. RESULTS: In total, 371 AIH patients (median age 49 years, 32% reported advanced fibrosis) completed the questionnaire. Respondents were 91% women, 89% Caucasian, and 89% from North America. Ninety-three (25%) respondents were ever CBD users, with 55 of them (15% of the survey responders) identified as current users. Among ever users, 45.7% reported their treating doctors were aware of their CBD use. The most common reason cited for CBD use was pain (68%), poor sleep (62%), and fatigue (38%). Most respondents using CBD for these symptoms reported a significant improvement in pain (82%), sleep (87%), and fatigue (61%). In ever CBD users, 17.3% were able to stop a prescription medication because of CBD use: pain medication (47%), immunosuppression (24%), and sleep aids (12%). Side effects attributed to CBD use were reported in 3% of CBD users, yet there were no reported emergency department visits or hospitalizations. CONCLUSION: CBD use was not uncommon in patients with AIH, and its use was associated with reports of improvement in extrahepatic symptoms.
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Canabidiol/administração & dosagem , Hepatite Autoimune/tratamento farmacológico , Automedicação , Adulto , Canabidiol/efeitos adversos , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Medição de Risco , Automedicação/efeitos adversos , Mídias Sociais , Fatores de Tempo , Resultado do TratamentoRESUMO
SIGNIFICANCE: This study reports prevalence data combined independently for accommodative dysfunction, convergence insufficiency, visual field loss, and visual acuity loss in patients with traumatic brain injury in the absence of eye injury. OBJECTIVE: The objective of this study was to conduct a systematic review and meta-analysis to determine the prevalence rates of accommodative dysfunction, convergence insufficiency, visual field loss, and visual acuity loss in TBI patients without concomitant eye injury. DATA SOURCES: The data sources used in this study were PubMed, EMBASE, EBSCO, and Cochrane Library. STUDY APPRAISAL AND SYNTHESIS METHODS: Publications reporting the prevalence of diagnosed accommodative dysfunction, convergence insufficiency, visual field loss, or visual acuity loss to the level of legal blindness in TBI patients of any age were included. Univariate metaregression analyses and subgroup analyses were performed to account for statistical heterogeneity. RESULTS: Twenty-two eligible publications were identified across the four visual conditions. Random-effects models yielded combined prevalence estimates: accommodative dysfunction (42.8; 95% confidence interval [CI], 31.3 to 54.7), convergence insufficiency (36.3%; 95% CI, 28.2 to 44.9%), visual field loss (18.2%; 95% CI, 10.6 to 27.1%), and visual acuity loss (0.0%; 95% CI, 0.0 to 1.1%). Metaregression and subgroup analyses revealed that visual field loss was significantly more prevalent in moderate to severe (39.8%; 95% CI, 29.8 to 50.3%) compared with mild TBI (6.6%; 95% CI, 0 to 19.5%). CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: This study demonstrates that accommodative dysfunction, convergence insufficiency, and visual field loss are common sequelae of TBI. Prospective longitudinal research with rigorous and uniform methodology is needed to better understand short- and long-term effects of TBI on the vision system.
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Lesões Encefálicas Traumáticas/complicações , Transtornos da Motilidade Ocular/etiologia , Transtornos da Visão/etiologia , Acomodação Ocular/fisiologia , Lesões Encefálicas Traumáticas/fisiopatologia , Humanos , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia , Campos Visuais/fisiologiaRESUMO
Noncirrhotic portal hypertension (NCPH) is often a diagnostic challenge due to signs and symptoms of portal hypertension that overlap with cirrhosis. The etiology of NCPH is broadly classified as prehepatic, hepatic (presinusoidal and sinusoidal) and posthepatic. Some common etiologies of NCPH encountered in clinical practice include portal vein thrombosis (prehepatic) and nodular regenerative hyperplasia (hepatic). Liver histology, although considered gold standard to exclude cirrhosis in individuals with suspected NCPH, is often limited by subtle histologic features or inadequate sampling. Liver stiffness measurements (LSMs) by vibration-controlled transient elastography may provide clinically important information to distinguish NCPH from cirrhosis by revealing normal LSM in prehepatic and presinusoidal NCPH.
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Técnicas de Imagem por Elasticidade , Hipertensão Portal/diagnóstico , Cirrose Hepática/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: Social decision making has recently been evaluated in alcohol use disorder (AUD) using the ultimatum game (UG) task, suggesting a possible deficit in aversive emotion regulation elicited by the unfairness during this task. Despite the relevance to relapse of this possible faulty regulation, the brain correlates of the UG in AUD are unknown. METHODS: In total, 23 AUD and 27 healthy controls (HC) played three consecutive fMRI runs of the UG, while behavioral and brain responses were recorded. RESULTS: Overall, acceptance rate of unfair offers did not differ between groups, but there was a difference in the rate of behavioral change across runs. We found significant anterior insula (aINS) activation in both groups for both fair and unfair conditions, but only HC showed a trend towards increased activation during unfair vs. fair offers. There were not overall whole-brain between-group significant differences. We found a trend of signal attenuation, instead of an increase, in the aINS for AUD when compared to HC during the third run, which is consistent with our recent findings of selective insula atrophy in AUD. CONCLUSION: We found differential group temporal dynamics of behavioral response in the UG. The HC group had a low acceptance rate for unfair offers in the first two runs that increased markedly for the third run; whereas the AUD group was consistent in their rejection of unfair offers across the three runs. We found a strong significant decrease in neural response across runs for both groups. SHORT SUMMARY: This fMRI study of UG in alcohol use disorder found behavioral group differences in acceptance rate across runs, which together with significant BOLD-signal decrease across runs in UG-related regions in both groups, highlights the impairment of strategy in AUD and the effect of repetitive exposure to unfairness in this task.
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Alcoolismo/diagnóstico por imagem , Alcoolismo/psicologia , Córtex Cerebral/diagnóstico por imagem , Tomada de Decisões/fisiologia , Emoções/fisiologia , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Distribuição Aleatória , Tempo de Reação/fisiologia , Comportamento SocialRESUMO
Alcohol dependence is characterized by impulsiveness toward consumption despite negative consequences. Although neuro-imaging studies have implicated some regions underlying this disorder, there is little information regarding its large-scale connectivity pattern. This study investigated the within- and between-network functional connectivity (FC) in alcohol dependence and examined its relationship with clinical impulsivity measures. Using probabilistic independent component analysis on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 alcohol-dependent (AD) and 26 healthy control (HC) participants, we compared the within- and between-network FC between AD and HC. Then, the relationship between FC and impulsiveness as measured by the Barratt Impulsiveness Scale (BIS-11), the UPPS-P Impulsive Scale and the delay discounting task (DDT), was explored. Compared with HC, AD exhibited increased within-network FC in salience (SN), default mode (DMN), orbitofrontal cortex (OFCN), left executive control (LECN) and amygdala-striatum (ASN) networks. Increased between-network FC was found among LECN, ASN and SN. Between-network FC correlations were significantly negative between Negative-Urgency and OFCN pairs with right executive control network (RECN), anterior DMN (a-DMN) and posterior DMN (p-DMN) in AD. DDT was significantly correlated with the between-network FC among the LECN, a-DMN and SN in AD. These findings add evidence to the concept of altered within-network FC and also highlight the role of between-network FC in the pathophysiology of AD. Additionally, this study suggests differential neurobiological bases for different clinical measures of impulsivity that may be used as a systems-level biomarker for alcohol dependence severity and treatment efficacy.
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Alcoolismo/fisiopatologia , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Comportamento Impulsivo/fisiologia , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Masculino , Descanso , Adulto JovemRESUMO
BACKGROUND: To comprehensively examine the cardiovascular health of Canadians, we developed the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) health index. We analyzed trends in health behaviours and factors to monitor the cardiovascular health of the Canadian population. METHODS: We used data from the Canadian Community Health Survey (2003-2011 [excluding 2005]; response rates 70%-81%) to examine trends in the prevalence of 6 cardiovascular health factors and behaviours (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes and hypertension) among Canadian adults aged 20 or older. We defined ideal criteria for each of the 6 health metrics. The number of ideal metrics was summed to create the CANHEART health index; values range from 0 (worst) to 6 (best or ideal). A separate CANHEART index was developed for youth age 12-19 years; this index included 4 health factors and behaviours (smoking, physical activity, fruit and vegetable consumption and overweight/obesity). We determined the prevalence of ideal cardiovascular health and the mean CANHEART health index score, stratified by age, sex and province. RESULTS: During the study period, physical activity and fruit and vegetable consumption increased and smoking decreased among Canadian adults. The prevalence of overweight/obesity, hypertension and diabetes increased. In 2009-2010, 9.4% of Canadian adults were in ideal cardiovascular health, 53.3% were in intermediate health (4-5 healthy factors or behaviours), and 37.3% were in poor cardiovascular health (0-3 healthy factors or behaviours). Twice as many women as men were in ideal cardiovascular health (12.8% vs. 6.1%). Among youth, the prevalence of smoking decreased and the prevalence of overweight/obesity increased. In 2009-2010, 16.6% of Canadian youth were in ideal cardiovascular health, 33.7% were in intermediate health (3 healthy factors or behaviours), and 49.7% were in poor cardiovascular health (0-2 healthy factors or behaviours). INTERPRETATION: Fewer than 1 in 10 Canadian adults and 1 in 5 Canadian youth were in ideal cardiovascular health from 2003 to 2011. Intensive health promotion activities are needed to meet the Heart and Stroke Foundation of Canada's goal of improving the cardiovascular health of Canadians by 10% by 2020 as measured by the CANHEART health index.