Colorectal Cancer Screening Receipt Does Not Differ by 10-Year Mortality Risk Among Older Adults.

BACKGROUND: Health status and life expectancy are important considerations for assessing potential benefits and harms of colorectal cancer (CRC) screening programs, particularly among older adults. METHODS: We examined receipt of past-year CRC screening according to predicted 10-year mortality risk among 25,888 community-dwelling adults aged 65-84 years who were not up-to-date with screening in the nationwide National Health Interview Survey. Ten-year mortality risk was estimated using a validated index; from the lowest to highest quintiles of the index, risk was 12%, 24%, 39%, 58%, and 79%, respectively. We also examined the proportion of screening performed among adults with life expectancy <10 years. RESULTS: The prevalence of past-year CRC screening was 39.5%, 40.6%, 38.7%, 36.4%, and 35.4%, from the lowest to highest quintile of 10-year mortality risk. Odds of CRC screening did not differ between adults in the lowest vs highest quintile (adjusted odds ratio 1.05, 95% confidence interval: 0.93-1.20). One-quarter (27.9%) of past-year CRC screening occurred in adults with life expectancy <10 years, and more than half (50.7%) of adults aged 75-84 years had 10-year mortality risk ≥50% at the time of screening. In an exploratory analysis, invasive but not noninvasive screening increased as 10-year mortality risk increased ( P < 0.05) among adults aged 70-79 years. DISCUSSION: Past-year CRC screening does not differ by predicted 10-year mortality risk. An age-based approach to CRC screening results in underscreening of older, healthier adults and overscreening of younger adults with chronic conditions. Personalized screening with incorporation of individual life expectancy may increase the value of CRC screening programs.

Cryptogenic hepatocellular carcinoma: characteristics, outcome, and prognostic role of albumin-bilirubin (ALBI) grade vs easy ALBI grade.

BACKGROUND: The characteristics and prognosis of cryptogenic hepatocellular carcinoma (HCC) remain unclear. The albumin-bilirubin (ALBI) grade and its updated version, the easy ALBI (EZ-ALBI) grade, are important prognostic predictors for HCC. We aimed to investigate the long-term survival of patients with cryptogenic HCC and the prognostic role of ALBI and EZ-ALBI grade in these patients. METHODS: A prospective cohort of 2,937 HCC patients with viral or cryptogenic etiology were retrospectively analyzed. The multivariate Cox model was used to determine prognostic predictors. RESULTS: Cryptogenic HCC patients were often older and diabetic, had lower serum ɑ-fetoprotein (AFP) levels, larger tumor burden, poor performance status, advanced cancer stage, and received non-curative treatments compared with hepatitis B or C-related HCC. The Cox analysis showed that age > 65 years, serum AFP > 400 ng/mL, presence of vascular invasion or distant metastasis, presence of ascites, performance status 2-4, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatment, were independent predictors of decreased survival in cryptogenic HCC (p < .001). Significant survival differences were found across ALBI grade and EZ-ALBI grade in cryptogenic HCC and subgroup patients receiving curative or non-curative treatments. The Cancer of Liver Italian Program was the best staging system for patients with cryptogenic HCC. CONCLUSIONS: Patients with cryptogenic HCC have a larger tumor burden and advanced cancer stage at disease presentation compared with those with viral HCC. The ALBI and EZ-ALBI score are robust models to evaluate liver functional reserve for these patients independent of treatment modality.

Albumin-Based Liver Reserve Models vs. MELD 3.0 in Prognostic Prediction for Hepatocellular Carcinoma Patients with Renal Insufficiency.

The severity of liver functional reserve is an important prognostic predictor in hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI), easy (EZ)-ALBI, platelet-albumin-bilirubin (PALBI), platelet-albumin (PAL) score, and MELD 3.0 score are used to evaluate the severity of liver dysfunction. However, their prognostic role in HCC patients, specifically with renal insufficiency (RI), is unclear. We aimed to investigate the predictive accuracy of the five models in these patients. A total of 1120 newly diagnosed HCC patients with RI were enrolled. A multivariate Cox proportional analysis was used to identify independent predictors associated with survival. In the Cox model, older age, an α-fetoprotein ≥20 ng/mL, vascular invasion, a medium and high tumor burden score, poor performance status, a higher ALBI grade, an EZ-ALBI grade, a PALBI grade, a PAL grade, and MELD 3.0 score were all independently associated with decreased overall survival (all p < 0.001). Among the five liver reserve models, the ALBI grade is the best surrogate marker to represent liver functional reserve in terms of outcome prediction. The albumin-based liver reserve models (ALBI, EZ-ALBI, PALBI, and PAL) and MELD 3.0 are all feasible prognostic markers to indicate liver injury, specifically in HCC patients with RI. Among them, the ALBI grade is the most robust tool for survival prediction in these patients.

Frequency of Bowel Movements and Risk of Diverticulitis.

OBJECTIVE: The etiology of diverticulitis is poorly understood. The long-held belief that constipation and low-fiber diet are risk factors for diverticulosis has recently been challenged by studies that suggest that more frequent bowel movements predispose to diverticulosis. We aim to prospectively explore the association between bowel movement frequency and incident diverticulitis. DESIGN: We studied participants of the Nurses' Health Study (NHS) and Health Professional Follow-up Study (HPFS). Participants' medical history, lifestyle factors and diet were used in Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios(HRs) and 95% confidence intervals(CI). RESULTS: In the NHS during over 24 years of follow-up encompassing 1,299,922 person-years, we documented 5,214 incident cases of diverticulitis, and in the HPFS over 14 years encompassing 368,661 person-years of follow-up, we documented 390 incident cases of diverticulitis. We observed an inverse association between the frequency of bowel movements and risk of diverticulitis. In the NHS, compared with women who had daily bowel movements, those with more than once daily bowel movements had a HR of 1.30 (95% CI, 1.19, 1.42) and those with less frequent bowel movements had a HR of 0.89 (95% CI, 0.82, 0.95; p-trend < 0.0001). In the HPFS, the corresponding HRs were 1.29 (95% CI, 1.04, 1.59) and 0.61 (95% CI, 0.36, 1.03; p-trend = 0.003). The association between bowel movements and diverticulitis was not modified by categories of age, BMI, physical activity, laxative use or fiber intake. CONCLUSION: More frequent bowel movements appear to be a risk factor for subsequent diverticulitis both in men and women. Further studies are needed to understand the potential mechanisms that may underlie this association.

Hypochloremia as a novel adverse prognostic factor in acute liver failure.

BACKGROUND AND AIMS: Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America. METHODS: The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21-day all-cause mortality or requirement for liver transplantation (death/LT). RESULTS: Patients with hypochloremia (<98 mEq/L) had a significantly higher 21-day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant-free cumulative survival in the hypochloremic group than in the normo- or hyper-chloremic groups (log-rank, χ2 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21-day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969-0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13-0.25) but underestimated the probability of transplant-free survival in 34% of patients (NRI = -0.34, 95% CI: -0.39 to -0.28). CONCLUSIONS: Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG-Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT.

History of Diverticulitis and Risk of Incident Cardiovascular Disease in Men: A Cohort Study.

BACKGROUND: Diverticulitis and cardiovascular disease (CVD) are two highly prevalent disorders sharing common risk factors which are hypothesized to have an inflammatory basis. AIMS: To examine the association between history of diverticulitis and risk of incident CVD. METHODS: We conducted a prospective cohort study of 43,904 men aged 40 to 75 years without a history of CVD (fatal or nonfatal myocardial infarction and stroke) at enrollment who were followed up from 1986 to 2012 in the Health Professionals Follow-Up Study. Lifestyle factors, dietary intake, and disease information were self-reported biennially or quadrennially. Incident diverticulitis and CVD were confirmed by review of medical records. We used Cox proportional hazard models to calculate age- and multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) of incident CVD. We conducted a stratified analysis according to the presence or absence of CVD risk factors (smoking, hypertension, hyperlipidemia, and diabetes). RESULTS: We identified 3848 incident cases of CVD during 856,319 person-years of follow-up. Men with diverticulitis had higher incidence of CVD (727 cases per 100,000 person-years) compared to men without diverticulitis [446 cases per 100,000 person-years, multivariate HR of 1.35 (95% CI 1.07-1.70)]. The association of diverticulitis and subsequent CVD appeared more evident among men without known CVD risk factors (HR 4.06, 95% CI 2.04-8.08) compared to those with one or more CVD risk factors (HR 1.27, 95% CI 0.98-1.63). CONCLUSIONS: Diverticulitis may be an independent risk factor of incident CVD, suggesting possible common etiopathogenic mechanisms. Diagnosis of diverticulitis underscores the importance of preventive measures to reduce future CVD.

Dual hepatitis B and C-associated hepatocellular carcinoma: clinical characteristics, outcome, and prognostic role of albumin-bilirubin grade.

BACKGROUND: Albumin-bilirubin (ALBI) grade is used to evaluate the outcome of patients with hepatocellular carcinoma (HCC) which is often associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study aimed to investigate the clinical characteristics, outcome, and prognostic role of ALBI grade in dual HBV/HCV-related HCC. METHODS: A total 3341 HCC patients with viral etiology were prospectively enrolled and retrospectively analyzed. Multivariate Cox proportional hazards model was used to identify independent prognostic predictors. RESULTS: Of all patients, 2083 (62%), 1068 (32%), and 190 (6%) patients had HBV, HCV, and dual HBV/HCV infection, respectively. The mean age of HBV, HCV, and dual virus group was 60, 68, and 64 years (p < 0.001), respectively. There was no significant survival difference between HBV, HCV, and dual HBV/HCV-related HCC group (p = 0.712). Multivariate Cox analysis in dual HBV/HCV-related HCC showed that multiple tumors [hazard ratio (HR): 1.537, p = 0.044], tumor size >3 cm (HR 2.014, p = 0.044), total tumor volume (TTV) >50 cm3 (HR 3.050, p < 0.001), vascular invasion (HR 3.258, p < 0.001), performance status 2-4 (HR 2.232, p < 0.001), ALBI grade 2-3 (HR 2.177, p < 0.001), and BCLC stage B-D (HR 2.479, p < 0.001) were independent predictors of poor survival. CONCLUSIONS: Dual viral infection does not accelerate the development of HCC in HBV carriers. Patient survival is similar between dual HBV/HCV-related HCC and single HBV- or HCV-related HCC group. The ALBI grade is a robust prognostic model in dual virus-related HCC to discriminate patient long-term survival.

Easy albumin-bilirubin score as a new prognostic predictor in hepatocellular carcinoma.

BACKGROUND: Liver functional reserve is a major prognostic determinant in patients with hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI) score is an objective method to assess the severity of cirrhosis in this setting. However, calculation of the ALBI score is complex and difficult to access in clinical practice. Recently, the EZ (easy)-ALBI score was proposed as an alternative biomarker of liver injury. We aimed to evaluate the prognostic role of the EZ-ALBI score in HCC from early to advanced stages. METHODS: A total of 3794 newly diagnosed HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were determined by using the multivariate Cox proportional hazards model. RESULTS: The EZ-ALBI score showed good correlation with the ALBI score (correlation coefficient, 0.965; p < 0.001). The correlation of the EZ-ALBI score was highly preserved in different Child-Turcotte-Pugh (CTP) classifications, treatment methods, and Barcelona Clinic Liver Cancer (BCLC) stages (correlation coefficients, 0.90-0.97). In the Cox multivariate analysis, age >65 years, male sex, serum α-fetoprotein >20 ng/ml, large or multiple tumors, total tumor volume >100 cm3 , vascular invasion or distant metastasis, ascites, poor performance status, EZ-ALBI grade 2 and 3, and noncurative treatments were independently associated with increased mortality (all p < 0.05). Moreover, EZ-ALBI grade can stratify long-term survival in patients with different CTP class, treatment strategy, and BCLC stage. CONCLUSIONS: The EZ-ALBI score is an easy and feasible method to evaluate liver functional reserve. As a new prognostic biomarker in HCC, the predictive power of the EZ-ALBI grade is independent across different cancer stages and treatments.

Tumor burden score as a new prognostic marker for patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BACKGROUND AND AIM: Size and number are major determinants of tumor burden in hepatocellular carcinoma (HCC). Patients with HCC undergoing transarterial chemoembolization (TACE) have variable outcomes due to heterogeneity of tumor burden. Recently, tumor burden score (TBS) was proposed to evaluate the extent of tumor involvement. However, the prognostic accuracy of TBS has not been well evaluated in HCC. This study aimed to assess its prognostic role in HCC patients undergoing TACE. METHODS: A total of 935 treatment-naïve HCC patients receiving TACE were retrospectively analyzed. Multivariate Cox proportional hazards model was used to determine independent prognostic predictors. RESULTS: Tumor burden score tended to increase with increasing size and number of tumors in study patients. The Cox model showed that serum creatinine ≥ 1.2 mg/dL (hazard ratio [HR]: 1.296, 95% confidence interval [CI]: 1.077-1.559, P = 0.006), serum α-fetoprotein ≥ 400 ng/dL (HR: 2.245, 95% CI: 1.905-2.645, P < 0.001), vascular invasion (HR: 1.870, 95% CI: 1.520-2.301, P < 0.001), medium TBS (HR: 1.489, 95% CI: 1.206-1.839, P < 0.001) and high TBS (HR: 2.563, 95% CI: 1.823-3.602, P < 0.001), albumin-bilirubin (ALBI) grade 2-3 (HR: 1.521, 95% CI: 1.291-1.792, P < 0.001), and performance status 1 (HR: 1.362, 95% CI: 1.127-1.647, P < 0.001) and status 2 (HR: 1.553, 95% CI: 1.237-1.948, P < 0.001) were associated with increased mortality. Patients with high TBS had poor overall survival in Barcelona Clinic Liver Cancer stage B/C and different ALBI grades. CONCLUSIONS: Tumor burden score is a feasible new prognostic surrogate marker of tumor burden in HCC and can well discriminate survival in patients undergoing TACE across different baseline characteristics.

Albumin-Bilirubin (ALBI) Grade-Based Nomogram for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

BACKGROUND/AIM: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is highly heterogeneous because of variable characteristics of tumor burden and liver dysfunction. We aimed to propose and validate an albumin-bilirubin (ALBI) grade-based prognostic nomogram for HCC patients undergoing TACE. METHODS: A total of 1051 patients with HCC undergoing TACE were randomly assigned to derivation (n = 525) and validation (n = 526) set in this retrospective study based on prospective data. The multivariate Cox proportional hazards model in derivation set was used to generate the nomogram. The predictive accuracy of the nomogram was evaluated by discrimination and calibration tests. RESULTS: In multivariate analysis, presence of ascites, ALBI grade 2-3, serum ɑ-fetoprotein level ≥ 400 ng/mL, total tumor volume ≥ 396 cm3, presence of vascular invasion, and poor performance status were independently associated with decreased survival of patients in the derivation set. Each patient had an individualized score from 0 to 41 by adding up the points from these six prognostic predictors. The nomogram generated from the derivation set had a concordance index of 0.72 (95% confidence interval [CI] 0.63-0.82). Discrimination test in the validation set provided a good concordance index 0.72 (95% CI 0.62-0.81), and the calibration plots consistently matched the ideal 45-degree reference line for 3- and 5-year survival prediction. CONCLUSIONS: The ALBI grade-based prognostic model can well discriminate the survival in HCC patients undergoing TACE. The proposed easy-to-use nomogram may accurately predict the survival at 3 and 5 years for individual HCC patient in the precision medicine era.

Association Between Inflammatory Diets, Circulating Markers of Inflammation, and Risk of Diverticulitis.

BACKGROUND & AIMS: Lifestyle and dietary risk factors for diverticulitis also have been associated with chronic inflammation. We performed a prospective study of associations among the inflammatory potential of diets, circulating markers of inflammation, and the incidence of diverticulitis. METHODS: We followed 46,418 men, initially free of diverticulitis, from 1986 through 2014 in the Health Professionals Follow-Up Study. We collected data on empiric dietary inflammatory pattern scores, which indicate the inflammatory potential of diets, and determined their association with the risk of incident diverticulitis using Cox proportional hazards regression. We used blood samples provided by 18,225 participants from 1993 through 1995 to conduct a nested case-control study; we used conditional logistic regression to evaluate prediagnostic plasma levels of markers of inflammation, including C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor-receptor superfamily member 1B, in 310 diverticulitis cases and 310 matched diverticulitis-free individuals (controls). RESULTS: We documented 1110 cases of incident diverticulitis over 992,589 person-years of follow-up. Compared with participants in the lowest quintile of empiric dietary inflammatory pattern scores, men in the highest quintile had a multivariable-adjusted hazard ratio for diverticulitis of 1.31 (95% CI, 1.07-1.60; Ptrend = .01). The association did not differ significantly by strata of body mass index or vigorous activity (P for interaction > .05 for each). In the nested case-control study, plasma levels of CRP and IL6 were associated with risk of diverticulitis. When we compared extreme quintiles, the multivariable-adjusted relative risk for diverticulitis was 1.85 for CRP (95% CI, 1.04-3.30) and 2.04 for IL6 (95% CI, 1.09-3.84). CONCLUSIONS: In a large prospective cohort of men, we found that the inflammatory potential of diet and prediagnostic plasma levels of markers of inflammation were associated with incident diverticulitis.

Thrombocytosis is associated with worse survival in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Thrombocytosis is associated with more aggressive tumour biology in many malignancies. There are limited data in patients with hepatocellular carcinoma (HCC), which often occurs in patients with cirrhosis and portal hypertension. We aimed to explore the prognostic value of thrombocytosis in two cohorts of patients with HCC. METHODS: We included 3561 patients from Taiwan and 1145 patients from the USA. Thrombocytopenia was defined as platelet count < 150×109 /L and thrombocytosis as ≥ 300 × 109 /L at HCC diagnosis. We used multivariable Cox proportional hazard models to identify independent predictors of survival. RESULTS: Thrombocytosis was present in 9.0% and 6.9% of Taiwan and USA patients respectively. Compared to patients with normal platelet counts and those with thrombocytopenia, patients with thrombocytosis had larger tumours, increased vascular invasion and a higher proportion had extrahepatic metastases in both cohorts. In multivariable analysis, thrombocytosis (aHR 1.40, 95% CI 1.23-1.60) and thrombocytopenia (aHR 1.13, 95% CI 1.04-1.23) were both associated with worse survival after adjusting for age, gender, liver disease aetiology, Child-Pugh score, maximal tumour size, tumour nodularity, vascular invasion, lymph node or distant metastasis, performance status and alpha-fetoprotein level. Patients with thrombocytosis had a median survival of 6 and 4 months in the Taiwan and USA cohorts, compared to 32 and 14 months for those with normal platelet counts and 38 and 16 months for thrombocytopenic patients. CONCLUSION: Thrombocytosis is independently associated with increased tumour burden and worse overall survival among HCC patients.

Albumin-bilirubin grade-based nomogram of the BCLC system for personalized prognostic prediction in hepatocellular carcinoma.

BACKGROUND & AIMS: The prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. We aimed to develop and validate an albumin-bilirubin (ALBI) grade-based nomogram of BCLC to estimate survival for individual HCC patient. METHODS: Between 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analysed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram. RESULTS: Beta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3- and 5-year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71-0.81) in the derivation cohort and 0.76 (95% CI: 0.71-0.81) in the validation cohort. The calibration plots to predict both 3- and 5-year survival rate well matched with the 45-degree ideal line for both cohorts, except for ALBI-based BCLC stage 0 in the validation cohort. CONCLUSIONS: The proposed ALBI-based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and user-friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.

Fruit and vegetable consumption is associated with lower prevalence of asymptomatic diverticulosis: a cross-sectional colonoscopy-based study.

BACKGROUND: Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis. METHODS: Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDER), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: Among 549 participants with a mean age of 61 years enrolled in GIDER, we confirmed diverticulosis in 245 (44.6%). The prevalence of diverticulosis appeared to decrease with higher consumption of fruit and vegetables (Ptrend = 0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60-1.17) with five to seven servings per week and 0.62 (95% CI, 0.44-0.89) with greater than one serving per day. Similarly, compared to participants with less than five servings per week of fruit, the multivariable-adjusted PR of diverticulosis was 0.60 (95% CI, 0.41-0.87) with greater than one serving per day. These associations were not modified by age, BMI, smoking, or red meat intake (All Pinteraction > 0.055). CONCLUSION: In a colonoscopy-based longitudinal cohort study, we show that higher consumption of fruit and vegetables is associated with lower risk of prevalent diverticulosis.

Differential Survival Impact of Diabetes Mellitus on Hepatocellular Carcinoma: Role of Staging Determinants.

BACKGROUND: Diabetes mellitus (DM) is common in patients with hepatocellular carcinoma (HCC) and may impact survival. Very few studies focused on the influence of DM in different clinical scenarios. We evaluated the prognostic impact of DM on HCC patients stratified by liver dysfunction, Milan criteria, and performance status defined in the Barcelona Clínic Liver Cancer staging parameters. METHODS: A prospective dataset of 3573 HCC patients between 2002 and 2016 was retrospectively analyzed. The multivariate Cox proportional hazards model was used to identify independent prognostic predictors. The Kaplan-Meier method with a log-rank test was applied to compare the survival distributions between different patient groups. RESULTS: Among all, DM was not an independent prognostic predictor in the Cox multivariate analysis (p = 0.1044). In the subgroup analysis, DM was not a significant prognostic predictor in Child-Turcotte-Pugh class A or class B/C patients. However, DM was associated with a decreased survival in patients within the Milan criteria (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.155-1.601, p = 0.0002) and in those with the performance status 0 (HR 1.213, 95% CI 1.055-1.394, p = 0.0067) in the multivariate Cox analysis, but not in those beyond the Milan criteria and poor performance status. CONCLUSIONS: DM is highly prevalent in HCC patients and has a distinct survival impact. DM is an independent survival predictor among patients within the Milan criteria and good performance status. These high-risk patients should be closely monitored, and aggressive anticancer treatment should be considered.

A New Prognostic Model Based on Albumin-Bilirubin Grade for Hepatocellular Carcinoma Beyond the Milan Criteria.

BACKGROUND: The survival of patients with advanced hepatocellular carcinoma (HCC) is highly variable due to heterogeneous tumoral characteristics. We proposed and validated an albumin-bilirubin (ALBI)-based model for HCC beyond Milan criteria, the ALBI-HOME, for these patients. METHODS: A total of 2186 patients were enrolled and randomly assigned to the derivation cohort (n = 1093) and validation cohort (n = 1093). Multivariate Cox proportional hazards model was used to determine significant prognostic factors in the derivation cohort. The performance of ALBI-HOME was evaluated in the validation cohort. RESULTS: In the Cox model, six factors were identified as independent predictors of poor survival: ALBI grade 2 [hazard ratio (HR) 1.848, 95% confidence incidence (CI) 1.556-2.195, p < 0.001], ALBI grade 3 (HR 3.266, 95% CI 2.531-4.215, p < 0.001), serum AFP ≥ 100 ng/ml (HR 1.482, 95% CI 1.279-1.717, p < 0.001), total tumor volume ≥ 250 cm3 (HR 1.503, 95% CI 1.294-1.746, p < 0.001), ascites (HR 1.400, 95% CI 1.187-1.561, p < 0.001), performance status 0-1 (HR 1.756, 95% CI 1.485-2.076 p < 0.001), and vascular invasion or metastasis (HR 2.110, 95% CI 1.809-2.0, p < 0.001). The ALBI-HOME is based on these six parameters, and the score ranges from 0 to 7. This model was associated with the best prognostic ability among different HCC staging systems to predict survival in patients beyond Milan criteria; its ability remained consistently stable in different treatment subgroups and viral etiologies. CONCLUSIONS: The proposed ALBI-HOME is a simple and feasible predictive model for HCC beyond Milan criteria. It demonstrates superior prognostic performance among the currently used staging systems and may help identify at-risk patients to undergo more aggressive treatments.

Identification of Menopausal and Reproductive Risk Factors for Microscopic Colitis-Results From the Nurses' Health Study.

BACKGROUND & AIMS: Microscopic colitis is a chronic inflammatory disorder of the colon primarily affecting postmenopausal women. However, the relation between hormonal determinants, including reproductive and menopausal factors, and risk of microscopic colitis has yet to be characterized. METHODS: We collected data from 227,766 women who participated in the Nurses' Health Study (NHS) and the NHSII without a baseline history of microscopic colitis. Reproductive and menopausal factors were assessed in 1988 in the NHS and 1989 in the NHSII and updated biennially. Cases of microscopic colitis were confirmed through review of pathology records. We used Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals. RESULTS: Through 2014 in the NHS and 2015 in the NHSII, we confirmed 275 incident cases of microscopic colitis over 5,147,282 person-years. Compared with never use, current use of menopausal hormone therapy was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 2.64; 95% confidence interval 1.78-3.90). The risk increased with longer duration of use (P for trend < .0001) and decreased after discontinuation (P for trend = .002). The association did not differ according to disease subtype (P for heterogeneity = .34). Similarly, ever use of oral contraceptives was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 1.57; 95% confidence interval 1.16-2.13). There were no associations between age at menarche, parity, age at first birth, age at menopause, or menopause type and incident microscopic colitis. CONCLUSIONS: In 2 large prospective cohort studies, we observed an association between exogenous hormone use and incident microscopic colitis. Further studies are needed to determine the mechanisms underlying these associations.

Association Between Obesity and Weight Change and Risk of Diverticulitis in Women.

BACKGROUND & AIMS: There is little evidence that adiposity associates with diverticulitis, especially among women. We conducted a comprehensive evaluation of obesity, weight change, and incidence of diverticulitis in a large cohort of women. METHODS: We conducted a prospective cohort study of 46,079 women enrolled in the Nurses' Health Study who were 61-89 years old and free of diverticulitis, diverticular bleeding, cancers, or inflammatory bowel disease at baseline (in 2008). We used Cox proportional hazards models to examine the associations among risk of incident diverticulitis and body mass index (BMI), waist circumference, waist to hip ratio, and weight change from age 18 years to the present. The primary end point was first incident diverticulitis requiring antibiotic therapy or hospitalization. RESULTS: We documented 1084 incident cases of diverticulitis over 6 years of follow-up, encompassing 248,001 person-years. After adjustment for other risk factors, women with a BMI ≥35.0 kg/m2 had a hazard ratio for diverticulitis of 1.42 (95% confidence interval [CI], 1.08-1.85) compared to women with a BMI <22.5 kg/m2. Compared to women in the lowest quintile, the multivariable hazard ratios among women in the highest quintile were 1.35 (95% CI, 1.02-1.78) for waist circumference and 1.40 (95% CI, 1.07-1.84) for waist to hip ratio; these associations were attenuated with further adjustment for BMI. Compared to women maintaining weight from age 18 years to the present, those who gained ≥20 kg had a 73% increased risk of diverticulitis (95% CI, 27%-136%). CONCLUSIONS: During a 6-year follow-up period, we observed an association between obesity and risk of diverticulitis among women. Weight gain during adulthood was also associated with increased risk.

Obesity and Weight Gain Since Early Adulthood Are Associated With a Lower Risk of Microscopic Colitis.

BACKGROUND & AIMS: Obesity promotes intestinal inflammation and might contribute to the pathogenesis of inflammatory bowel disease. We examined the association between obesity and risk of microscopic colitis in a prospective cohort study. METHODS: We collected data from 192,101 women enrolled in the Nurses' Health Study (NHS) (from 1986 through 2014) or the NHSII (from 1991 through 2015). Anthropomorphic and lifestyle information were self-reported biennially. Obesity was defined using body mass index (BMI). Microscopic colitis was confirmed by review of medical records. We used Cox proportional hazard models to estimate adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: Among the participants in the NHS and NHSII, we confirmed 244 cases of microscopic colitis during 4,223,868 person-years of follow-up evaluation. Higher BMI was associated inversely with risk of microscopic colitis (Ptrend < .001). Compared with women with BMIs ranging from 18.5 to 20.9 kg/m2, the aHRs were 0.61 (95% CI, 0.41-0.91) for overweight women (BMI, 25-29.9 kg/m2) and 0.50 (95% CI, 0.32-0.79) for obese women (BMI ≥ 30 kg/m2). The aHR for each 5-kg/m2 increase in BMI was 0.79 (95% CI, 0.69-0.90). Weight gain since early adulthood (age, 18 y) also was associated inversely with risk of microscopic colitis (Ptrend = .001). The aHR for each 10-kg weight gain since early adulthood was 0.85 (95% CI, 0.77-0.94). The associations were not modified by age, cohort, physical activity, or smoking status (all Pinteraction ≥ .26). CONCLUSIONS: Unlike many other immune- and metabolic-related disorders, obesity and weight gain since early adulthood were associated with a lower risk of microscopic colitis, based on an analysis of participants in the NHS and NHSII.

Intake of Dietary Fiber, Fruits, and Vegetables and Risk of Diverticulitis.

OBJECTIVES: Although low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited in women despite having a disproportionate burden of disease, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of fiber including fruits and vegetables with risk of diverticulitis in a large cohort of women. METHODS: We followed 50,019 women in the Nurses' Health Study (1990-2014) who were aged 43-70 years and free of diverticulitis, cancer, and inflammatory bowel disease at baseline. Incident diverticulitis was identified through self-report with validity confirmed by review of medical records. RESULTS: We documented 4,343 incident cases of diverticulitis, encompassing 1,106,402 person-years of follow-up. Compared with participants in the lowest quintile, the multivariable hazard ratio of diverticulitis in the highest quintile of total fiber intake was 0.86 (95% confidence interval: 0.78-0.95; P-trend = 0.002). Fiber from fruits and cereals, but not vegetables, was associated with a decreased risk of diverticulitis. Furthermore, intake of total whole fruit intake and specific fruits such as apples/pears and prunes were associated with reduced risk of diverticulitis with a multivariable hazard ratio for diverticulitis of 0.95 (0.92-0.98; P-trend < 0.001) for every serving increase of total whole fruit intake per day. DISCUSSION: Higher intake of dietary fiber and fiber from different food sources, except for vegetable fiber, are associated with a lower risk of diverticulitis in women. A greater intake of whole fruit is also associated with reduced risk.