Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia.

Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

Prevalence of exocrine pancreatic insufficiency at 12 months after acute pancreatitis: a prospective, multicentre, longitudinal cohort study.

Background: Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort. Methods: In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 µg/g; severe FE-1 level ≤100 µg/g; mild FE-1 101-200 µg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398. Findings: EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%). Interpretation: EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening. Funding: This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc.

Clinicopathologic Characteristics of Thyroid Microcarcinoma: Findings from a Hospital-Based Study in Vietnam.

BACKGROUND: Thyroid microcarcinoma (TMC) incidence has significantly increased in recent decades. The rates of lymph node metastasis extrathyroidal extension have been significantly different in patients with TMC ≤5 mm versus those with size >5 mm. The current analysis aimed to examine the clinicopathologic features of TMC measuring <5 mm and to compare them with those of TMC ≥5 mm. METHODS: A total of 273 patients with TMC confirmed by histological examination from December 2020 to May 2021 were enrolled in Bach Mai Hospital, Hanoi, Vietnam. Unconditional logistic regression models were used to determine the association between clinicopathological factors and tumor size, central lymph node metastasis and extrathyroidal extension. RESULTS: We found 212/273 patients (77.7%) were diagnosed incidentally. The majority of patients were female (87.5%) and had a mean age of 44.2 years. The mean tumor size (±standard deviation (SD)) was 5.72 ± 2.33 mm. Most of the patients were also diagnosed with papillary TMC. Multifocal and bilateral lesions accounted for 13.2% and 12.1%, respectively. The extrathyroidal invasion was observed in 14.7% (40 patients), while 24.5% (67 patients) were those with central lymph node metastases. The rate of extrathyroidal extension in patients with tumor size ≥5 mm was significantly higher than in patients with tumor size <5 mm (odds ratio (OR) = 4.98; 95% confidence interval (CI): 1.48-16.70; p = 0.004). Patients with body mass index (BMI) <23 kg/m2 were found to be protected against the odds of extrathyroidal extension (OR = 0.38, 95% CI: 0.19-0.75; p = 0.004) compared to those with BMI ≥23 kg/m2. In univariable mode, central lymph node metastasis was positively associated with the odds of the presence of extrathyroidal extension (OR = 2.70, 95% CI: 1.34-5.45; p = 0.004). In the multivariable model, central lymph node metastasis was also associated with the presence of extrathyroidal extension (OR = 2.507, 95% CI: 1.194-5.264; p = 0.017). Univariate analysis demonstrated that tumor size ≥5 mm (OR = 2.04; 95% CI: 1.01-4.17; p = 0.047) and extrathyroidal extension (OR = 2.71; 95% CI: 1.34-5.45; p = 0.004) were risk factors of central cervical lymph node metastasis. In multivariable models, the extrathyroidal extension was associated with central lymph metastasis. CONCLUSIONS: TMC <5 mm tumor size is less likely to have aggressive characteristics, including extrathyroidal extension, than a TMC ≥5 mm. Long-term follow-up studies are thus warranted to investigate the factors in the prognosis of TMC.

Protective effect of early immunomodulatory treatment on ocular involvement in Behcet's disease: Historical cohort of 1166 patients.

Objectives: Eye involvement is a main presentation of Behcet's disease. This study was performed to evaluate possible determinants affecting the occurrence of eye involvement, especially the role of early systemic treatment with immunomodulatory drugs on the incidence of ocular involvement. Methods: This is a retrospective cohort study performed on 1166 Behcet's patients in the Behcet's Clinic of Rheumatology Research Center. All patients were followed up for at least 10 years and a maximum of 15 years. Data analysis was performed using survival analysis models including Kaplan-Meier Survival analysis, Logrank test, and Cox's proportional hazards regression. Results: 1166 Behcet's patients were evaluated. 80 patients who had eye involvement as the first manifestation of the disease were excluded and 1086 participants entered the analysis. Among them, 647 patients (59.6%) developed ocular involvement 7.8 ± 6.7 years after the first symptom. Immunomodulatory treatment before ocular involvement reduced the risk by 3 times (P-value <0.001). Conclusion: This study demonstrated that the initiation of immunomodulatory treatment prior to eye involvement can reduce the risk of eye involvement in Behcet's patients. Therefore, reducing the onset time of disease symptoms and providing appropriate treatment can reduce Behcet's disease ocular complications.

Incident diabetes following acute pancreatitis in a multicenter prospective observational cohort.

Diabetes mellitus following an episode of acute pancreatitis (AP) is an increasingly discussed complication, but there are sparse prospective data on the incidence and risk factors. We evaluated data from a prospective, multicenter observational cohort study that enrolled adults hospitalized with AP between 2017 and 2021 and followed them for one year. Ninety-eight participants who completed 12-month follow-up were included in this analysis. Diabetes status was assessed using a combination of measured glycated hemoglobin (HbA1c) at predetermined time intervals or physician diagnosis. In 68 participants without diabetes at enrollment, the cumulative incidence of new-onset diabetes was 4.4 % (n = 3) at 3 months and 10.3 % (n = 7) at 12 months. No differences were observed in demographic or pancreatitis-related characteristics between those who did versus did not develop diabetes, in part due to small sample size. In summary, new-onset diabetes was identified in approximately 10 % within one year after an episode of AP. Larger prospective studies are needed to further define the incidence, risk factors, and mechanisms of diabetes and pre-diabetes following AP. NCT03063398.

Relationship of circulating levels of long-chain fatty acids to persistent organ failure in acute pancreatitis.

During acute pancreatitis (AP), free fatty acids (FFAs) are liberated from circulating triglycerides (TG) and injured adipocytes by pancreatic lipase. Circulating FFAs have been suspected as a source of systemic lipotoxicity in AP. However, assessment of FFAs is difficult and time-consuming, and little is known about relative levels of FFAs between patients with different severities of AP and controls. This study's aims were to assess early circulating levels of FFAs, (both saturated and unsaturated) in patients with AP vs. controls, and associations between FFA levels and AP severity. Serum samples from patients with AP were collected at enrollment (day 1 of hospital stay); serum samples were also collected from controls. FFAs including palmitic, palmitoleic, stearic, oleic, and linoleic acid were extracted and quantitated using gas chromatography separation. Severity of AP was determined by Revised Atlanta Classification. Differences in FFA levels and percentages of total FFAs were assessed between patients with AP and controls and patients with AP of different severity grades. A total of 93 patients with AP (48 female, 52%) and 29 controls (20 female, 69%) were enrolled. Of the patients with AP, 74 had mild/moderate and 19 had severe AP. Serum levels of all FFAs except stearic acid were significantly higher in patients with AP compared with controls. A strong and independent association between elevated palmitoleic acid levels and severe AP was found. Serum unsaturated FFA levels, specifically palmitoleic acid, appear to correlate with severe AP. These findings have potential clinical implications for targeted AP therapies.NEW & NOTEWORTHY Drivers of the inflammatory response in acute pancreatitis remain incompletely understood. Unsaturated fatty acids, specifically palmitoleic, appear to have an association with more severe acute pancreatitis. This finding presents a new clinical understanding of fatty acid toxicity and highlights a potential future target for treatment in severe acute pancreatitis.

The Association Between Serum Riboflavin and Flavin Mononucleotide With Pancreatic Cancer: Findings From a Prospective Cohort Study.

OBJECTIVES: Vitamin B2 (riboflavin) has a prime role in metabolic reactions imperative to cell cycle and proliferation. We investigated the associations between serum concentrations of riboflavin flavin mononucleotide with the risk of pancreatic cancer in a nested case-control study involving 58 cases and 104 matched controls. METHODS: The Singapore Chinese Health Study, an ongoing prospective cohort study of 63,257 Chinese Singaporeans. Conditional logistic regression method was used to evaluate these associations with adjustment for potential confounders including the level of education, body mass index, smoking status, alcohol consumption, history of diabetes, serum cotinine and pyridoxal 5'-phosphate, estimated glomerular filtration rate, and total methyl donors (ie, the sum of serum choline, betaine, and methionine). RESULTS: The risk of pancreatic cancer increased with increasing level of serum riboflavin in a dose-dependent manner, especially in men (Ptrend = 0.003). The odds ratio (95% confidence intervals) of pancreatic cancer for the second and third tertiles of serum riboflavin, compared with the lowest tertile, were 9.92 (1.65-59.77) and 25.59 (3.09-212.00), respectively. This positive association was stronger in individuals with a longer follow-up period (≥7 years). CONCLUSIONS: The findings suggest a potential role of riboflavin in the development of pancreatic cancer, especially in men.

Incidence of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis.

BACKGROUND: HCC can develop in the absence of cirrhosis in patients with NAFLD. We aimed to estimate the incidence of HCC in patients with NAFLD with and without cirrhosis or advanced liver fibrosis. METHODS: We performed a cohort study to determine the incidence of HCC in patients with NAFLD identified by the International Classification of Diseases 9/10 codes in the electronic health records of a US health care system between 2004 and 2018. The incidence of HCC was stratified by the presence or absence of cirrhosis and by the Fibrosis-4 index (FIB-4) at the time of HCC diagnosis. RESULTS: Of 47,165 patients with NAFLD aged 40-89 years, 981 (2.1%) developed HCC (mean follow-up 3.4 y). Among patients with HCC, 842 (85.8%) had cirrhosis, while 139 (14.2%) did not. Of the 139 patients with HCC without cirrhosis-related diagnostic codes, 26 (2.7%) had FIB-4 >2.67 (advanced fibrosis likely), whereas 43 (4.4%) had FIB-4 < 1.30 (excluding advanced fibrosis). The annual incidence of HCC in patients with NAFLD with and without cirrhosis was 23.6 and 1.1 per 1000 person-years, respectively. Among patients without cirrhosis, the annual incidence of HCC was 2.8 per 1000 person-years with FIB-4 >2.67 and 0.7 per 1000 person-years with FIB-4 <1.30. Patients with NAFLD and cirrhosis were 31.8 times (95% CI, 23.3-43.4) more likely to develop HCC than those without cirrhosis and FIB-4 <1.30, after adjustment for age and sex. CONCLUSIONS: Patients with NAFLD without cirrhosis nor advanced fibrosis have a low incidence of HCC.

Lactated Ringers Use in the First 24 Hours of Hospitalization Is Associated With Improved Outcomes in 999 Patients With Acute Pancreatitis.

INTRODUCTION: Recent pilot trials in acute pancreatitis (AP) found that lactated ringers (LR) usage may result in decreased risk of moderately severe/severe AP compared with normal saline, but their small sample sizes limit statistical power. We investigated whether LR usage is associated with improved outcomes in AP in an international multicenter prospective study. METHODS: Patients directly admitted with the diagnosis of AP were prospectively enrolled at 22 international sites between 2015 and 2018. Demographics, fluid administration, and AP severity data were collected in a standardized prospective manner to examine the association between LR and AP severity outcomes. Mixed-effects logistic regression analysis was performed to determine the direction and magnitude of the relationship between the type of fluid administered during the first 24 hours and the development of moderately severe/severe AP. RESULTS: Data from 999 patients were analyzed (mean age 51 years, female 52%, moderately severe/severe AP 24%). Usage of LR during the first 24 hours was associated with reduced odds of moderately severe/severe AP (adjusted odds ratio 0.52; P = 0.014) compared with normal saline after adjusting for region of enrollment, etiology, body mass index, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume. DISCUSSION: LR administration in the first 24 hours of hospitalization was associated with improved AP severity. A large-scale randomized clinical trial is needed to confirm these findings.

Association between Sleep Duration and Colorectal Adenomas: Findings from a Case-Control Study in Vietnam.

BACKGROUND: Colorectal cancer is one of the leading cancers worldwide and in Vietnam. Adenomas are important precursors of colorectal cancer. Study on the association between sleep duration and development of colorectal adenoma (CRA) is limited, particularly among Vietnamese population. METHODS: We conducted an individually matched case-control study of 870 CRA cases and 870 controls in a large-scale colorectal screening program involving 103,542 individuals ages ≥40 years old in Hanoi, Vietnam. Sleep duration was categorized in three groups: short: ≤6 hours/day, normal: 7 to 8 hours/day, and long: >8 hours/day. Conditional logistic regression was used to evaluate the association between sleep duration and adenomas risk after controlling for potential confounders. RESULTS: Overall, short-sleep duration was associated with increased risk of having CRA compared with normal duration [OR, 1.48; 95% confidence interval (CI), 1.12-1.97]. This pattern was present in both females (OR, 1.58; 95% CI, 1.14-2.18) and males (OR, 1.45; 95% CI, 1.08-1.93), with advanced adenomas (OR, 1.61; 95% CI, 1.09-2.38) and non-advanced adenomas (OR, 1.66; 95% CI, 1.19-2.32). Furthermore, the association between CRA development and short-sleep duration was more apparent among females who were nondrinker, nonobese, physically active, with proximal or both sided adenomas and with cardiometabolic disorder. Among males, the short-sleep duration was associated with CRA risk among never-smoking, cardiometabolic disorders, and obese. CONCLUSIONS: Short-sleep duration was associated with increased prevalence of both advanced and non-advanced CRAs among Vietnamese population. IMPACT: Findings from this study showed that maintaining an adequate sleep duration may have an important implication for colorectal adenoma prevention and control.

Obesity and alcoholic etiology as risk factors for multisystem organ failure in acute pancreatitis: Multinational study.

BACKGROUND: Multisystem organ failure (MSOF) is the most important determinant of mortality in acute pancreatitis (AP). Obesity and alcoholic etiology have been examined as potential risk factors for MSOF, but prior studies have not adequately elucidated their independent effects on the risk of MSOF. OBJECTIVE: We aimed to determine the adjusted effects of body mass index (BMI) and alcoholic etiology on the risk of MSOF in subjects with AP. METHODS: A prospective observational study of 22 centers from 10 countries was conducted. Patients admitted to an APPRENTICE consortium center with AP between August 2015 and January 2018 were enrolled. Multivariable logistic regression was used to estimate the adjusted effects of BMI, etiology, and other relevant covariates on the risk of MSOF. Models were stratified by sex. RESULTS: Among 1544 AP subjects, there was a sex-dependent association between BMI and the risk of MSOF. Increasing BMI was associated with increased odds of MSOF in males (OR 1.10, 95% confidence interval [CI] 1.04-1.15) but not in females (OR 0.98, 95% CI 0.90-1.1). Male subjects with AP, whose BMIs were 30-34 and >35 kg/m2 , had odds ratios of 3.78 (95% CI 1.62-8.83) and 3.44 (95% CI 1.08-9.99), respectively. In females, neither higher grades of obesity nor increasing age increased the risk of MSOF. Alcoholic etiology was independently associated with increased odds of MSOF compared with non-alcohol etiologies (OR 4.17, 95% CI 2.16-8.05). CONCLUSION: Patients with alcoholic etiology and obese men (but not women) are at substantially increased risk of MSOF in AP.

High serum magnesium is associated with lower risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD. METHODS: A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow-up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking. RESULTS: Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p = .003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67-1.12), 0.77 (0.57-1.04), and 0.73 (0.56-0.96), respectively, after adjustment for multiple potential confounders (P trend  = .02). CONCLUSION: This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD.

Low-Carbohydrate Diet Score and the Risk of Colorectal Cancer: Findings from the Singapore Chinese Health Study.

BACKGROUND: Colorectal cancer is common cancer with a high mortality rate. Low-carbohydrate diet (LCD) score holistically evaluates the LCD pattern from carbohydrate, protein, and fat intake. Epidemiologic data of LCD-colorectal cancer association are sparse. METHODS: We evaluated the associations between LCD (i.e., total, animal- and plant-based) and colorectal cancer risk in the Singapore Chinese Health Study, a population-based prospective cohort study including 61,321 Chinese in Singapore who were 45 to 74 years old at baseline. Cox proportional hazard regression model was used to determine the HRs and respective 95% confidence intervals (CI) for colorectal cancer associated with LCD after adjusting for potential confounders, including age, sex, BMI, physical activity, family history of colorectal cancer, etc. RESULTS: After an average of 19.5 years of follow-up, 2,520 participants developed colorectal cancer (1,608 colon cancer and 912 rectal cancer). Overall, the association between total or plant-based LCD scores with the risk of colorectal, colon, or rectal cancer was null (all Ptrend ≥ 0.28). The animal-based LCD was modestly associated with colon cancer risk (Ptrend = 0.02), but not with rectal cancer. Compared with the lowest quartile, HRs (95% CIs) of colon cancer for quartiles 2, 3, and 4 of animal-based LCD were 1.12 (0.98-1.29), 1.27 (1.10-1.46), and 1.14 (0.99-1.31), respectively. CONCLUSIONS: A low-level carbohydrate diet with a high level of animal protein and fat was associated with a moderate increase in the risk of colon cancer among Chinese Singaporeans. IMPACT: High consumption of animal protein/fat and low consumption of carbohydrates may increase colon cancer risk.

Neutrophil-lymphocyte ratio in relation to risk of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease.

BACKGROUND: Blood neutrophil to lymphocyte ratio (NLR) or lymphocyte count may be important markers for immune function. Previous work has shown higher NLR was associated with higher risk of hepatitis B-related hepatocellular carcinoma (HCC). However, studies in non-alcoholic fatty liver disease (NAFLD) patients are lacking. METHODS: Utilizing the University of Pittsburgh Medical Center (UPMC) electronic health records, we created a retrospective cohort of 27,834 patients diagnosed with NAFLD from 2004 to 2018 with complete NLR data. After an average 5.5 years of follow-up, 203 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with different levels of NLR and lymphocyte count. RESULTS: Compared with the lowest tertile of NLR (<1.97), the highest tertile of NLR (≥3.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR = 1.43, 95% CI: 1.01-2.03, ptrend  = 0.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis-4 score category. Conversely the highest tertile of lymphocyte count (≥2.15 K/ul) was significantly associated with a 36% lower risk of HCC (HR = 0.64, 95% CI: 0.43-0.94, ptrend  = 0.028) compared to the lowest tertile (<1.55 K/ul). There was no association between neutrophil count and HCC risk. CONCLUSIONS: Higher NLR and lower lymphocyte count are associated with significantly higher risk of HCC among NAFLD patients. These findings warrant further investigation of immune response and surveillance in association with HCC development in NAFLD patients.

Dietary Nonstarch Polysaccharide Intake and Risk of Colorectal Cancer: Findings from the Singapore Chinese Health Study.

Dietary fiber or non-starch polysaccharides (NSP) may provide protection from CRC development. Epidemiologic studies on the association between dietary fiber and CRC is inconsistent are limited on NSP as a modifiable risk factor. Using the Singapore Chinese Health Study, a population-based prospective cohort of 61,321 cancer-free middle-aged or older Chinese Singaporeans, we examined the association between dietary fiber and NSP intakes and CRC risk. Fiber and NSP intakes at baseline were obtained using a validated semi-quantitative food frequency questionnaire coupled with the Singapore Food Composition Database. Cox proportional hazard regression model was used to estimate the hazard ratios (HRs) and respective 95% confidence intervals (CIs) for CRC associated with dietary fiber and NSP intakes after adjusting for potential confounders. After an average of 17.5 years of follow-up, 2,140 participants developed CRC. NSP was inversely associated with the risk of CRC in a dose-dependent manner whereas dietary fiber was not associated with risk of CRC overall or histologic subtypes. The multivariable-adjusted HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of dietary NSP intake were 0.99 (0.88-1.11), 0.98 (0.87-1.11) and 0.84 (0.73-0.95), respectively, compared with the lowest quartile (P trend =0.006). This inverse association was more apparent for colon cancer (HRQ4 vs. Q1=0.79, 95% CI: 0.67-0.93, P trend =0.003) than rectal cancer (HR Q4 vs. Q1=0.92, 95% CI: 0.74-1.13, P trend =0.53). Our findings suggested that dietary NSP but not fiber is associated with a reduced risk of colon cancer in Chinese Singaporeans. Significance: Non-starch polysaccharides may be beneficial for colorectal cancer primary prevention.

The Association between Peptic Ulcer Disease and Gastric Cancer: Results from the Stomach Cancer Pooling (StoP) Project Consortium.

BACKGROUND: Gastric cancer (GC) is the fifth most common type of cancer and the fourth most common cause of cancer-related mortality. Although the risk of GC and peptic ulcer disease (PUD) is known to be increased by H. pylori infection, evidence regarding the direct relationship between PUD and GC across ethnicities is inconclusive. Therefore, we investigated the association between PUD and GC in the Stomach cancer Pooling (StoP) consortium. METHODS: History of peptic ulcer disease was collected using a structured questionnaire in 11 studies in the StoP consortium, including 4106 GC cases and 6922 controls. The two-stage individual-participant data meta-analysis approach was adopted to generate a priori. Unconditional logistic regression and Firth's penalized maximum likelihood estimator were used to calculate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between gastric ulcer (GU)/duodenal ulcer (DU) and risk of GC. RESULTS: History of GU and DU was thoroughly reported and used in association analysis, respectively, by 487 cases (12.5%) and 276 controls (4.1%), and 253 cases (7.8%) and 318 controls (6.0%). We found that GU was associated with an increased risk of GC (OR = 3.04, 95% CI: 2.07-4.49). No association between DU and GC risk was observed (OR = 1.03, 95% CI: 0.77-1.39). CONCLUSIONS: In the pooled analysis of 11 case-control studies in a large consortium (i.e., the Stomach cancer Pooling (StoP) consortium), we found a positive association between GU and risk of GC and no association between DU and GC risk.

Severe acute pancreatitis exhibits distinct cytokine signatures and trajectories in humans: a prospective observational study.

Severe acute pancreatitis (SAP) is associated with substantial morbidity and mortality. Several cytokines have been identified to have pathophysiological significance in SAP, but studies characterizing their early trajectories are lacking. Here we characterize the early trajectories of seven key cytokines associated with SAP and compare them with non-SAP subjects. Five proinflammatory cytokines (angiopoietin-2, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, resistin) and two anti-inflammatory cytokines (hepatocyte growth factor, and soluble tumor necrosis factor-α receptor-1A) were measured in a prospective cohort of acute pancreatitis subjects (2012-2016) at the time of enrollment and then every 24 h for 5 days or until discharge. The cytokines' levels and trajectories were calibrated based on date of pain onset and were compared between healthy controls and three severity categories (mild, moderate, and severe). The cohort (n = 170) consisted of 27 healthy controls, 65 mild, 38 moderate, and 40 SAP. From day 1 of symptom onset, SAP subjects exhibited significantly higher levels of both pro- and anti-inflammatory cytokines compared with non-SAP and healthy subjects. But in SAP subjects, all proinflammatory cytokines' levels trended downward after day 2 (except for a flat slope for angiopoeitin-2) whereas for non-SAP subjects, the trajectory was upward: this trajectory difference between SAP versus non-SAP subjects resulted in narrowing of the differences initially seen on day 1 for proinflammatory cytokines. For anti-inflammatory cytokines, the trajectories were uniformly upward for both SAP and non-SAP subjects. Proinflammatory cytokine response is an early and time-sensitive event in SAP that should be accounted for when designing future biomarker studies and/or therapeutic trials.NEW & NOTEWORTHY In this study, we showed that the proinflammatory cytokine response in SAP is an early event, with subsequent downregulation of proinflammatory cytokines beginning at day 1 of symptom onset. Our findings underscore the importance of enrolling subjects very early in the disease course when conducting studies to investigate early immune events of SAP; this current study also serves as an important reference for the design of future biomarker studies and therapeutic trials in SAP.

The Association between Serum Serine and Glycine and Related-Metabolites with Pancreatic Cancer in a Prospective Cohort Study.

Background. Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine and glycine with pancreatic cancer risk. Methods. We conducted a nested case-control study involved 129 incident pancreatic cancer cases and 258 individually matched controls within a prospective cohort study of 18,244 male residents in Shanghai, China. Glycine and serine and related metabolites in pre-diagnostic serum were quantified using gas chromatography-tandem mass spectrometry. A conditional logistic regression method was used to evaluate the associations for serine, glycine, and related metabolites with pancreatic cancer risk with adjustment for potential confounders. Results: Odds ratios (95% confidence intervals) of pancreatic cancer for the highest quartile of serine and glycine were 0.33 (0.14−0.75) and 0.25 (0.11−0.58), respectively, compared with their respective lowest quartiles (both p's < 0.01). No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. Conclusion. The risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of glycine and serine in serum collected, on average, more than 10 years prior to cancer diagnosis in a prospectively designed case-control study. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for cancer prevention.

Composite dietary antioxidant index and the risk of colorectal cancer: Findings from the Singapore Chinese Health Study.

Colorectal cancer (CRC) is a major contributor to cancer death globally. Several studies showed some protections by certain individual dietary antioxidants against CRC development. Epidemiologic data on the composite dietary antioxidant index (CDAI) in relation to CRC risk are sparse. Using the Singapore Chinese Health Study, an ongoing prospective cohort consisting of 61 321 cancer-free participants aged 45 to 74 years at baseline, a food-based CDAI was calculated according to a previously established and validated method that included six food-sourced antioxidants including vitamins A, C and E, manganese, selenium and zinc. Cox proportional hazard regression method was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for CRC associated with various levels of CDAI with adjustment for multiple potential confounders. After an average of 17.5 years of follow-up, 2140 participants developed CRC. HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of CDAI were 0.94 (0.83-1.07), 0.86 (0.75-1.00) and 0.80 (0.66-0.98), respectively, compared to the lowest quartile (Ptrend  = .02). This inverse association between CDAI and CRC risk was more apparent in women or those without a history of diabetes, without family history of CRC, never smokers or overweight/obese individuals. However, none of the heterogeneity tests for the CDAI-CRC risk association reached statistical significance. Our findings suggest that food-based antioxidants may be beneficial for reducing the risk of CRC in the general population.

The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study.

BACKGROUND & AIMS: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. METHODS: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. RESULTS: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). CONCLUSION: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.