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1.
Semin Liver Dis ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33788207

RESUMO

The success of liver transplant (LT) for hepatocellular carcinoma (HCC) is dependent on accurate tumor staging using validated imaging criteria, and adherence to acceptable criteria based on tumor size and number. Other factors including α-fetoprotein (AFP) and response to local regional therapy (LRT) have now played a larger role in candidate selection. Tumor downstaging is defined as reduction in the size of viable tumors using LRT to meet acceptable criteria for LT, and serves as a selection tool for a subgroup of HCC with more favorable biology. The application of tumor downstaging requires a structured approach involving three key components in tumor staging-initial tumor stage and eligibility criteria, tumor viability assessment following LRT, and target tumor stage prior to LT-and incorporation of AFP into staging and treatment response assessments. In this review, we provide in-depth discussions of the key role of these staging definitions in ensuring successful outcome.

2.
AJR Am J Roentgenol ; : 1-8, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33703926

RESUMO

OBJECTIVE. The purpose of this study was to identify risk factors for and outcomes of hepatotoxicity after selective chemoembolization of hepatocellular carcinoma. MATERIALS AND METHODS. This retrospective study included 182 patients (136 men and 46 women; median age, 63 years [interquartile range, 57-70 years]) who underwent 338 consecutive doxorubicin drug-eluting bead (DEB) chemoembolization procedures between 2011 and 2014. Outcomes were assessed until November 2019. In 97% of procedures, two or fewer segments were targeted. The Barcelona Clinic Liver Cancer (BCLC) stage was 0 or A for 77 procedures (22.8%), B for 75 (22.2%), C for 122 (36.1%), and D for 64 (18.9%). Hepatotoxicity was defined as worsened ascites or encephalopathy or as grade 3 or 4 elevations in liver function test results, creatinine levels, or the international normalized ratio within 30 days. Risk factors were assessed by univariate and multivariable generalized estimating equations. Transplant-free survival was assessed using Cox proportional hazard models. RESULTS. Hepatotoxicity was observed after 84 of 338 procedures (24.9%) performed for 70 of 182 patients (38.5%) and was irreversible for 40 procedures (11.8%). On multivariable analysis, risk factors for irreversible toxicity included Child-Pugh class C liver function (odds ratio [OR], 4.4; 95% CI, 1.0-19.0; p = .04), BCLC stage C (OR, 5.0; 95% CI, 1.6-16.0; p = .006) or D (OR, 7.4; 95% CI, 2.1-25.5; p = .002) disease, TIPS or hepatofugal portal venous flow (OR, 6.3; 95% CI, 2.3-17.0; p < .001), and a serum α-fetoprotein level of 200 ng/mL or greater (OR, 2.6; 95% CI, 1.1-6.1; p = .03). Irreversible toxicity was associated with reduced transplant-free survival among patients who were ineligible for liver transplant (hazard ratio, 2.5; standard error, 0.42; p = .03). CONCLUSION. Irreversible hepatotoxicity was common after selective chemoembolization in patients with advanced stage disease, an elevated serum α-fetoprotein level, or reduced hepatic portal venous perfusion, and it may hasten death among patients who are ineligible for liver transplant.

3.
Liver Transpl ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33570786

RESUMO

BACKGROUND: We assessed the prognostic significance and the clinical stability of NLR prior to LT in a large cohort of HCC patients from a long wait time region. A high preoperative neutrophil-to-lymphocyte (NLR) ≥ 5 has been reported to predict poor outcomes following liver transplantation (LT) for HCC, and NLR has been incorporated into several prognostic models. METHODS: We evaluated 758 HCC patients listed for LT with MELD exception from 2002-2015 at a single LT center, of which 505 underwent and 253 dropped out prior to LT. NLR was collected in all patients at LT and, if available, between 15-90 days prior to LT (NLR 2) or at dropout. RESULTS: NLR ≥ 5 was associated with microvascular invasion, poorer tumor differentiation, and more advanced pathology on explant. Patients with NLR ≥ 5 exhibited no differences in AFP, tumor burden at listing, or number of LRT compared to patients with NLR < 5. After a median post-LT follow-up of 4.7 years, overall survival and recurrence rates were similar for NLR ≥ 5 vs NLR < 5. The NLR changed frequently, and 47% of patients whose NLR2 was ≥ 5 had an NLR < 5 by LT. NLR was ≥ 5 in 47.6% of patients at dropout, compared with 14.9% of patients undergoing LT. CONCLUSIONS: While NLR at LT correlated with MVI and tumor stage at explant, NLR did not predict post-LT survival or HCC recurrence. NLR appeared to be a relatively unstable inflammatory marker over the immediate three months prior to LT for HCC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33524592

RESUMO

Among patients with hepatocellular carcinoma (HCC), elevated α-fetoprotein (AFP) has been shown to predict waitlist dropout, high-risk histopathologic features, and inferior post-liver transplant (LT) outcome.1,2 Nevertheless, many patients with HCC have a normal AFP and yet still experience waitlist dropout or post-LT recurrence.2 Because of the degree of imprecision associated with AFP, there is a quest for other biomarkers that may be complementary to or better than AFP in predicting prognosis in LT. Lectin-reactive AFP (AFP-L3) and des-gamma-carboxyprothrombin (DCP) are biomarkers that have been used in conjunction with AFP as HCC surveillance or diagnostic tools.3,4 However, the utility of these biomarkers in LT for HCC is not established.

5.
Ann Epidemiol ; 56: 18-25, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33493649

RESUMO

PURPOSE: To identify life-long body mass index (BMI) trajectories across two related generations and estimate their associated mortality risks and population attributable deaths. METHODS: We use prospective cohort data from the Framingham Heart Study (1948-2011) original (4576 individuals, 3913 deaths) and offspring (3753 individuals, 967 deaths) cohorts and latent trajectory models to model BMI trajectories from age 31 to 80 years. Survival models are used to estimate trajectory-specific mortality risk. RESULTS: We define seven BMI trajectories among original cohort and six among offspring cohort. Among original cohort, people who are normal weight at age 31 years and gradually move to overweight status in middle or later adulthood have the lowest mortality risk even compared to those who maintain normal weight throughout adulthood, followed by overweight stable, lower level of normal weight, overweight downward, class I obese upward, and class II/III upward trajectories. Mortality risks associated with obesity trajectories have declined across cohorts, while the prevalence of high-risk trajectories has increased. CONCLUSIONS: The mortality impact of weight gain depends on an individual's BMI trajectory. Population attributable deaths associated with unhealthy weight trajectories have grown over generations because the prevalence has increased, offsetting the decline in trajectory-specific mortality risks.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33279780

RESUMO

BACKGROUND: &AIMS: Early liver transplantation (LT) for alcoholic hepatitis (AH) is lifesaving but concerns regarding return to harmful alcohol use remain. We sought to identify distinct patterns of alcohol use post-LT to inform pre-LT candidate selection and post-LT addiction care. METHODS: Detailed post-LT alcohol use data was gathered retrospectively from consecutive patients with severe AH at 11 ACCELERATE-AH sites from 2006-2018. Latent class analysis identified longitudinal patterns of alcohol use post-LT. Logistic and Cox regression evaluated associations between patterns of alcohol use with pre-LT variables and post-LT survival. A microsimulation model estimated the effect of selection criteria on overall outcomes. RESULTS: Of 153 LT recipients, 1-, 3-, and 5-year survival were 95%, 88% and 82%. Of 146 LT recipients surviving to home discharge, four distinct longitudinal patterns of post-LT alcohol use were identified: Pattern 1 [abstinent](n=103;71%), pattern 2 [late/non-heavy](n=9;6.2%), pattern 3 [early/non-heavy](n=22;15%), pattern 4 [early/heavy](n=12;8.2%). One-year survival was similar among the 4 patterns (100%), but patients with early post-LT alcohol use had lower 5-year survival (62% and 53%) compared to abstinent and late/non-heavy patterns (95% and 100%). Early alcohol use patterns were associated with younger age, multiple prior rehabilitation attempts, and overt encephalopathy. In simulation models, the pattern of post-LT alcohol use changed the average life-expectancy after early LT for AH. CONCLUSIONS: A significant majority of LT recipients for AH maintain longer-term abstinence, but there are distinct patterns of alcohol use associated with higher risk of 3- and 5-year mortality. Pre-LT characteristics are associated with post-LT alcohol use patterns and may inform candidate selection and post-LT addiction care.

7.
Mol Metab ; : 101133, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33271332

RESUMO

OBJECTIVE: Nonalcoholic hepatic steatosis, also known as fatty liver, is a uniform response of the liver to hyperlipidic-hypercaloric diet intake. However, the post-ingestive signals and the mechanistic processes driving hepatic steatosis are not well understood. Emerging data demonstrate that protein kinase C beta (PKCß), a lipid-sensitive kinase, plays a critical role in energy metabolism and adaptation to environmental and nutritional stimuli. Despite its powerful effect on glucose and lipid metabolism, knowledge of the physiological roles of hepatic PKCß in energy homeostasis is limited. METHODS: The floxed-PKCß and hepatocyte-specific PKCß deficient mouse models were generated to study the in vivo role of hepatocyte PKCß on diet-induced hepatic steatosis, lipid metabolism, and mitochondrial function. RESULTS: We report that hepatocyte-specific PKCß deficiency protects mice from development of hepatic steatosis induced by high-fat diet, without affecting body weight gain. This protection is associated with attenuation of SREBP-1c transactivation and improved hepatic mitochondrial respiratory chain. Lipidomic analysis identified significant increases in the critical mitochondrial inner membrane lipid, cardiolipin, in PKCß-deficient livers compared to control. Moreover, hepatocyte PKCß deficiency had no significant effect on either hepatic or whole-body insulin sensitivity supporting dissociation between hepatic steatosis and insulin resistance. CONCLUSIONS: The above data indicate that hepatocyte PKCß is a key focus of dietary lipid perception and is essential for efficient storage of dietary lipids in liver largely through coordinating energy utilization and lipogenesis during postprandial period. These results highlight the importance of hepatic PKCß as a drug target for obesity-associated nonalcoholic hepatic steatosis.

8.
Transplantation ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33323764

RESUMO

BACKGROUND: Women with chronic liver disease have lower rates of hepatocellular carcinoma (HCC) as compared to men; it is unknown if there are sex-based differences in HCC recurrence post-liver transplant. METHODS: We conducted an analysis of patients who underwent liver transplant for HCC in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2012 through December 31, 2017. RESULTS: A total of 12,711 patients underwent liver transplant for HCC: 2,909 (23%) women and 9,802 (73%) men. Women had significantly lower rates of post-liver transplant HCC recurrence than men (4.0 v. 5.4%, p=0.002). A cox-regression analysis for post-liver transplant HCC recurrence highlighted that even after accounting for etiology of cirrhosis, alpha-fetoprotein (AFP) at liver transplant, tumor diameter, tumor pathology, and vascular invasion, female sex was associated with a 25% lower risk of post-liver transplant HCC recurrence (95CI 0.57-0.99). There were no interactions between female sex and the following variables: age, type of locoregional therapy, AFP, donor sex, body mass index, or nonalcoholic steatohepatitis etiology (p>0.05 for each). CONCLUSIONS: This study demonstrates an independent effect of sex on risk for HCC recurrence post-liver transplant. Our data highlight an opportunity to better understand HCC tumor biology by investigating the drivers of this sex-based difference in HCC recurrence.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33337478

RESUMO

AIMS: This meta-analysis provides summary odds ratio (OR) estimates for associations between treatment with (vs. without) renin-angiotensin system (RAS) blockers and risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and coronavirus disease 2019 (CoViD-19) severity (including case-fatality) in patients with hypertension, and in all patients (irrespective of hypertension). METHODS AND RESULTS: PubMed, EMBASE, Web of Science, Google Scholar, medRxiv and SSRN were searched (May 02, 2020 to August 12, 2020) for non-randomised observational CoViD-19 studies. Event/patient numbers were extracted, comparing ACE inhibitor/ARB treatment (and each separately), to treatment with neither drug, for the outcomes: (a) Likelihood of SARS-CoV-2 infection; (b) CoViD-19 severity (including hospitalisation, Intensive Therapy Unit (ITU), ventilation); (c) Case-fatality. Risk of bias was assessed (ROBINS-I). Random-effects meta-analysis estimates were pooled. Eighty six studies including 459,755 patients (103,317 with hypertension), were analysed. In patients with hypertension, ACE inhibitor or ARB treatment was not associated with a greater likelihood of SARS-CoV-2 infection in 60,141 patients (OR 1.06, 95% CI 0.99-1.14), hospitalisation in 5,925 patients (OR 0.90, 0.62-1.31), ITU in 7,218 patients (OR 1.06, 0.73-1.56), ventilation (or ITU/ventilation/death) in 13,163 patients (OR 0.91, 0.72-1.15) or case-fatality in 18,735 patients with 2,893 deaths (OR 0.75, 0.61-0.92). CONCLUSION: ACE inhibitors and ARBs appear safe in the context of SARS-CoV-2 infection and should not be discontinued. PROSPERO registration number: CRD42020186996.

10.
J Hepatol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33188904

RESUMO

BACKGROUND & AIMS: It has been suggested that patients with hepatocellular carcinoma (HCC) at high risk of waitlist dropout would have done poorly after liver transplantation (LT) due to tumor aggressiveness. To test this hypothesis, we analyzed risk of waitlist dropout among HCC patients in long wait regions (LWR) to create a dropout risk score, and applied this score in short (SWR) and mid wait regions (MWR) to evaluate post-LT outcomes. We sought to identify a threshold in dropout risk that predicts worse post-LT outcome. METHODS: Using the UNOS database including all patients with T2 HCC receiving priority listing from 2010-2014, a dropout risk score was created from a developmental cohort of 2,092 LWR patients, and tested in a validation cohort of 1,735 SWR and 2,894 MWR patients. RESULTS: On multivariable analysis, 1 tumor 3.1-5 cm or 2-3 tumors, AFP >20 ng/ml, and increasing Child-Pugh and MELD-Na scores significantly predicted waitlist dropout. A dropout risk score using these four variables (C-statistic 0.74) was able to stratify 1-year cumulative incidence of dropout from 7.1% with a score <7 to 39.5% with a score >23. Patients with a dropout risk score >30 had 5-year post-LT survival of 60.1% versus 71.8% for those with a score <30 (p=0.004). There were no significant differences in post-LT survival below this threshold. CONCLUSIONS: This study provided evidence that HCC patients with the highest dropout risk have aggressive tumor biology that would also result in poor post-LT outcomes when transplanted quickly. Below this threshold risk score of <30, priority status for organ allocation could be stratified based on the predicted risks of waitlist dropout without significant differences in post-LT survival.

11.
Transplant Direct ; 6(10): e605, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33134485

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of hepatocellular carcinoma (HCC) in the United States. Prior data suggest that NAFLD-HCC patients are less likely to receive liver transplantation (LT) and have worse overall survival; however, the reason for this discrepancy is unknown. Methods: We conducted a retrospective study of 631 HCC patients listed for LT at a large academic center from 2004 to 2013. Waitlist dropout and LT were analyzed using competing risk regression. Results: Compared with other-HCC patients (n = 589), NAFLD-HCC patients (n = 42, 6.7%) were older (65 versus 58, P < 0.001) with more women (50.0 versus 23.6%, P < 0.001), Hispanic ethnicity (40.5 versus 17.7%, P = 0.001), obesity (69.0 versus 29.9%, P < 0.001), diabetes mellitus (59.5 versus 27.8%, P < 0.01), insulin-dependence (23.8 versus 10.2%, P = 0.007), hyperlipidemia (40.5 versus 10.5, P < 0.001), and statin use (33.3 versus 5.3%, P < 0.001). Cumulative incidence of waitlist dropout at 2 y was 17.4% (95% confidence intervals, 7.7-30.4) for NAFLD HCC and 25.4% (95% confidence intervals, 21.9-29.0) for other HCC (P = 0.28). No difference in waitlist dropout or receipt of LT between NAFLD HCC and other HCC was found on regression analysis. Similarly, NAFLD and obesity, obesity alone, diabetes mellitus, insulin-dependence, hyperlipidemia, and statin use were not associated with waitlist outcomes. Finally, we observed no statistically significant difference in 5-y survival from HCC diagnosis between NAFLD HCC and other HCC (78.5% versus 66.9%, P = 0.9). Conclusions: In our single-center cohort, we observed no difference in waitlist outcomes or survival in NAFLD HCC, although conclusions are limited by the small number of NAFLD-HCC patients. Notably, the inclusion of patients with obesity in the NAFLD-HCC group and stratification by individual metabolic factors also showed no difference in waitlist outcomes.

12.
Clin Liver Dis ; 24(4): 665-679, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33012452

RESUMO

Hepatocellular carcinoma is a rising indication for liver transplantation in the United States. Downstaging, defined as the reduction of tumor burden using local-regional therapy into Milan criteria, opens an avenue to access cure through transplant for patients who traditionally would not qualify. Approaching the selection of downstaging candidates through an assessment of hepatic function, staying within a modest expansion of tumor burden, and incorporation of serologic/imaging markers for tumor biology provide the best chance for successful downstaging. Following well-defined downstaging protocols with built-in failure criteria ensures excellent post-transplant outcomes.

13.
JMIR Public Health Surveill ; 6(4): e21340, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33001831

RESUMO

BACKGROUND: The magnitude and time course of the COVID-19 epidemic in the United States depends on early interventions to reduce the basic reproductive number to below 1. It is imperative, then, to develop methods to actively assess where quarantine measures such as social distancing may be deficient and suppress those potential resurgence nodes as early as possible. OBJECTIVE: We ask if social media is an early indicator of public social distancing measures in the United States by investigating its correlation with the time-varying reproduction number (Rt) as compared to social mobility estimates reported from Google and Apple Maps. METHODS: In this observational study, the estimated Rt was obtained for the period between March 5 and April 5, 2020, using the EpiEstim package. Social media activity was assessed using queries of "social distancing" or "#socialdistancing" on Google Trends, Instagram, and Twitter, with social mobility assessed using Apple and Google Maps data. Cross-correlations were performed between Rt and social media activity or mobility for the United States. We used Pearson correlations and the coefficient of determination (ρ) with significance set to P<.05. RESULTS: Negative correlations were found between Google search interest for "social distancing" and Rt in the United States (P<.001), and between search interest and state-specific Rt for 9 states with the highest COVID-19 cases (P<.001); most states experienced a delay varying between 3-8 days before reaching significance. A negative correlation was seen at a 4-day delay from the start of the Instagram hashtag "#socialdistancing" and at 6 days for Twitter (P<.001). Significant correlations between Rt and social media manifest earlier in time compared to social mobility measures from Google and Apple Maps, with peaks at -6 and -4 days. Meanwhile, changes in social mobility correlated best with Rt at -2 days and +1 day for workplace and grocery/pharmacy, respectively. CONCLUSIONS: Our study demonstrates the potential use of Google Trends, Instagram, and Twitter as epidemiological tools in the assessment of social distancing measures in the United States during the early course of the COVID-19 pandemic. Their correlation and earlier rise and peak in correlative strength with Rt when compared to social mobility may provide proactive insight into whether social distancing efforts are sufficiently enacted. Whether this proves valuable in the creation of more accurate assessments of the early epidemic course is uncertain due to limitations. These limitations include the use of a biased sample that is internet literate with internet access, which may covary with socioeconomic status, education, geography, and age, and the use of subtotal social media mentions of social distancing. Future studies should focus on investigating how social media reactions change during the course of the epidemic, as well as the conversion of social media behavior to actual physical behavior.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vigilância em Saúde Pública/métodos , Mídias Sociais/estatística & dados numéricos , Número Básico de Reprodução , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/epidemiologia , Estados Unidos/epidemiologia
14.
Mucosal Immunol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060802

RESUMO

Interleukin-22 (IL-22) signaling in the intestines is critical for promoting tissue-protective functions. However, since a diverse array of cell types (absorptive and secretory epithelium as well as stem cells) express IL-22Ra1, a receptor for IL-22, it has been difficult to determine what cell type(s) specifically respond to IL-22 to mediate intestinal mucosal host defense. Here, we report that IL-22 signaling in the small intestine is positively correlated with Paneth cell differentiation programs. Our Il22Ra1fl/fl;Lgr5-EGFP-creERT2-specific knockout mice and, independently, our lineage-tracing findings rule out the involvement of Lgr5+ intestinal stem cell (ISC)-dependent IL-22Ra1 signaling in regulating the lineage commitment of epithelial cells, including Paneth cells. Using novel Paneth cell-specific IL-22Ra1 knockout mice (Il22Ra1fl/fl;Defa6-cre), we show that IL-22 signaling in Paneth cells is required for small intestinal host defense. We show that Paneth cell maturation, antimicrobial effector function, expression of specific WNTs, and organoid morphogenesis are dependent on cell-intrinsic IL-22Ra1 signaling. Furthermore, IL-22 signaling in Paneth cells regulates the intestinal commensal bacteria and microbiota-dependent IL-17A immune responses. Finally, we show ISC and, independently, Paneth cell-specific IL-22Ra1 signaling are critical for providing immunity against Salmonella enterica serovar Typhimurium. Collectively, our findings illustrate a previously unknown role of IL-22 in Paneth cell-mediated small intestinal host defense.

15.
Circ Arrhythm Electrophysiol ; 13(11): e007953, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33021815

RESUMO

The field of cardiac electrophysiology has been on the cutting edge of advanced digital technologies for many years. More recently, medical device development through traditional clinical trials has been supplemented by direct to consumer products with advancement of wearables and health care apps. The rapid growth of innovation along with the mega-data generated has created challenges and opportunities. This review summarizes the regulatory landscape, applications to clinical practice, opportunities for virtual clinical trials, the use of artificial intelligence to streamline and interpret data, and integration into the electronic medical records and medical practice. Preparation of the new generation of physicians, guidance and promotion by professional societies, and advancement of research in the interpretation and application of big data and the impact of digital technologies on health outcomes will help to advance the adoption and the future of digital health care.

16.
PLoS One ; 15(10): e0240904, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33091024

RESUMO

Little is known about body size over the life-course and non-communicable disease risk in low- and middle-income country populations. Our study explored the role of body mass index (BMI) trajectories from infancy through mid-adulthood on cardio-metabolic disease (CMD) risk factors in a prospective cohort of Guatemalan adults. Study participants were born in Guatemala from 1962-77 and have been followed prospectively since participating in a nutrition supplementation trial as children. Sex-specific BMI latent class trajectories were derived using latent class growth modeling from up to 22 possible BMI values from age 1 month to 42 years measured between 1969 and 2004. CMD risk factors were assessed in 2015-17 (at age 37-54 years) using anthropometry, blood glucose and lipids, and blood pressure. We used logistic regression to assess the role of BMI trajectory on CMD risk factors in 510 women and 346 men (N = 856). We identified two BMI latent classes for women (low [n = 287, 56.3%] and high [n = 223, 43.7%]) and three classes for men (low [n = 141, 40.8%], medium [n = 160, 46.2%], and high [n = 45, 13.0%]). Given the small percentage of men in the high BMI latent class, we collapsed the medium and high BMI latent classes for men (n = 205, 59.1%). Among the most prevalent CMD risk factors at ages 37-54 years were abdominal obesity defined by waist-height ratio (99.6% of women and 87.3% of men), obesity defined by percent body fat (96.6% of women and 75.9% of men), low HDL-c (87.5% of women and 74.5% of men), and elevated triglycerides (78.3% of women and 73.6% of men). Except for obesity defined by BMI, we found no associations between BMI latent class and CMD risk factors in women. Among men, BMI latent class was not associated with CMD risk factors after controlling for current BMI. For the CMD risk factors we analyzed, the role of early life BMI on adult CMD appeared to be mediated by adult BMI among men-highlighting the need to establish and maintain healthy body weight over the life course.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32927050

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers' opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient's HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 U.S. medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient's HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; p<0.001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; p<0.001). CONCLUSION: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.

18.
Expert Rev Gastroenterol Hepatol ; : 1-12, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32933351

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) is an increasingly common disease with liver transplant (LT) the best long-term therapy for early stage disease. We will review the data for assessing risk and managing recurrence for patients undergoing LT for HCC. AREAS COVERED: In this review, we will provide an overview of methods of patient risk stratification in the post-transplant period, the data around surveillance for HCC recurrence, and the evidence for and against post-LT adjuvant treatment strategies. Finally, we will provide data regarding treatment options for patients with HCC recurrence after LT. Using an extensive search of original papers and society guidelines, this paper provides a comprehensive review of the data for assessing risk and managing recurrence for patients undergoing LT for HCC. EXPERT OPINION: The development of multiple post-transplant prognostic scoring systems have allowed for improved assessment of recurrence risk and stratification of patients. However, the ability to translate this information into surveillance and therapeutic strategies that improve patient outcomes still have to be fully demonstrated. Post-LT immunosuppression strategies have been implemented in order to attempt to reduce this risk. Evidence-based strategies for managing recurrent HCC are evolving. We expect that with further understanding of individual patient characteristics will allow for optimal therapeutic selection.

20.
JAMA Cardiol ; 5(9): 1020-1026, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936273

RESUMO

Importance: The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. Objective: To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). Design, Setting, and Participants: Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. Exposures: History of taking ACEIs or ARBs at the time of COVID-19 testing. Main Outcomes and Measures: Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive. Results: A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). Conclusions and Relevance: This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adulto , Técnicas de Laboratório Clínico , Cuidados Críticos , Feminino , Hospitalização , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco
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