An Improved Assessment Method to Estimate (Poly)phenol Intake in Adults with Chronic Pancreatitis.

BACKGROUND: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped. AIMS: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data. METHODS: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample. RESULTS: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively. CONCLUSIONS: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.

Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial.

INTRODUCTION: Many oral nicotine pouch (ONP) brands use synthetic nicotine, which typically contains a racemic (50:50) mixture of nicotine's two stereoisomers: S-nicotine and R-nicotine. Because tobacco-derived nicotine contains more than 99% S-nicotine, the effects of R-nicotine in humans are not well known. We compared systemic nicotine exposure and product appeal of ONPs containing more than 99% S-nicotine versus racemic nicotine. AIMS AND METHODS: N = 18 adult smokers (Mage = 45 years, 66.7% male, 77.8% White) enrolled in a three-visit single-blind, randomized crossover study. During each visit, participants used one wintergreen-flavored, 3 mg nicotine ONP for 30 min following at least12 h nicotine abstinence. Study ONP #1 contained more than 99% S-nicotine and the other two study ONPs contained racemic nicotine (collapsed for analyses). Plasma nicotine assessments and measures of withdrawal relief occurred at t = 0, 5, 15, 30, 60, and 90 min; measures of product appeal were assessed following ONP use. RESULTS: Using the ONP with more than 99% S-nicotine resulted in greater plasma nicotine concentration from 15 to 90 min (p < .0001) and greater maximum plasma nicotine concentration than the ONPs with racemic nicotine (M = 9.9 ng/mL [SD = 2.5] vs. M = 5.7 ng/mL [SD = 2.8], respectively; p < .0001). Product liking and withdrawal relief were similar across ONPs, although participants reported more "bad effects" when using the ONP with more than 99% S-nicotine. CONCLUSIONS: Participants reported few subjective differences in ONPs according to nicotine stereoisomer, but plasma nicotine concentration was greater for ONPs using more than 99% S-nicotine. ONPs with more than 99% S-nicotine (vs. racemic nicotine) might be better substitutes for cigarettes, but research into other ONP characteristics (eg flavors, freebase nicotine) is needed to inform regulation. IMPLICATIONS: Little is known about the effects of racemic (vs. S-) nicotine in humans. In a sample of adults who smoke cigarettes, we identified that oral nicotine pouches containing racemic nicotine exposed participants to less nicotine than oral nicotine pouches containing only S-nicotine, but both types of oral nicotine pouches held similar, moderate appeal. Additional research evaluating the roles that flavorings, total nicotine concentration, and freebase nicotine play in the abuse liability of oral nicotine pouches would inform comprehensive product regulations to support public health.

Physical Activity Decreases Inflammation and Delays Development of Obesity-Associated Pancreatic Ductal Adenocarcinoma.

Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), a deadly disease with limited preventive strategies. Lifestyle interventions to decrease obesity represent a potential approach to prevent obesity-associated PDAC. Here, we examined whether decreasing obesity through physical activity (PA) and/or dietary changes could decrease inflammation in humans and prevent obesity-associated PDAC in mice. Comparison of circulating inflammatory-associated cytokines in subjects (overweight and obese) before and after a PA intervention revealed PA lowered systemic inflammatory cytokines. Mice with pancreatic-specific inducible KrasG12D expression were exposed to PA and/or dietary interventions during and after obesity-associated cancer initiation. In mice with concurrent diet-induced obesity (DIO) and KrasG12D expression, the PA intervention led to lower weight gain, suppressed systemic inflammation, delayed tumor progression, and decreased pro-inflammatory signals in the adipose tissue. However, these benefits were not as evident when obesity preceded pancreatic KrasG12D expression. Combining PA with diet-induced weight loss (DI-WL) delayed obesity-associated PDAC progression in the genetically engineered mouse model, but neither PA alone nor combined with DI-WL or chemotherapy prevented PDAC tumor growth in orthotopic PDAC models regardless of obesity status. PA led to upregulation of IL-15ra in adipose tissue. Adipose-specific overexpression of IL-15 slowed PDAC growth but only in non-obese mice. Overall, our study suggests that PA alone or combined with DI-WL can reduce inflammation and delay obesity-associated PDAC development or progression. Lifestyle interventions that prevent or manage obesity or therapies that target weight loss-related molecular pathways could prevent progression of PDAC.

An observational human laboratory assessment of nicotine delivery, vaping topography and subjective effects of usual brand electronic cigarette use among young adults.

AIMS: To measure nicotine delivery, vaping topography and subjective effects of current generations of disposable, cartridge-based and other types of electronic cigarettes (e-cigarettes) among young adults. DESIGN, SETTING, PARTICIPANTS: Observational, human laboratory assessment of e-cigarette use in Columbus, Ohio, USA (July 2020 to June 2021). Participants (n = 96, 60.4% female, age mean = 21.7 [standard deviation = 1.7] years, 82.4% white race) were identified via their participation in a cohort study or other convenience sampling and were 18 to 25 years old, vaped ≥4 days/week for ≥4 weeks and used other tobacco products for ≤5 days of past 30 days. Participants completed a pre-vaping questionnaire, vaped their usual brand of e-cigarette ad libitum for 30 min and completed a post-vaping questionnaire. MEASUREMENTS: Outcome variables included pre- and post-vaping measures of plasma nicotine (t = 0 and t = 30, respectively) and craving and withdrawal symptoms, as well as vaping topography (e.g. flow rate and inter-puff interval), pre-vaping expectancies and post-vaping product appeal. Variables used to characterize the sample included demographics, e-cigarette and other tobacco use history, e-cigarette dependence and e-cigarette device characteristics (e.g. device type, flavor and nicotine form). FINDINGS: Participants reported moderate nicotine dependence on average via the E-Cigarette Dependence Scale (mean = 6.9 [standard deviation = 4.0]). Following 30 min of ad libitum vaping, participants achieved substantial plasma nicotine boost (mean = 18.8 [standard deviation = 14.5] ng/mL), corresponding with statistically significant decreases in withdrawal symptoms measured via the Minnesota Nicotine Withdrawal Scale (pre-vaping mean = 9.0 [standard deviation = 5.1], post-vaping mean = 4.3 [standard deviation = 3.9]; P-value <0.0001). Pre-vaping, participants reported moderate vaping expectancies (e.g. mean = 2.5 [standard deviation = 1.0] on a scale from 0 to 4 for smell and taste expectancies); post-vaping, participants reported high satisfaction (mean = 4.6 [standard deviation = 1.2] on a scale from 1 to 7) and moderate reward (mean = 2.9 [standard deviation = 1.2]) and respiratory sensations (mean = 3.7 [standard deviation = 1.6]). Nearly half of participants (47.9%) used disposable e-cigarettes, and most used a mint/menthol or fruit flavored (99.0%) and nicotine salt (98.9%) e-liquid. CONCLUSIONS: Among young adults in the United States, the latest generations of e-cigarettes appear to deliver large quantities of nicotine (similar to cigarettes) and significantly relieve withdrawal symptoms, and they are appealing.

Examining the predictive utility of behavioral economic demand indices and subjective effects on the actualized reinforcing value of menthol cigarettes and potential alternatives.

INTRODUCTION: Considering recent and proposed bans on menthol cigarettes, methods are needed to understand the substitutability of potential menthol cigarette alternatives (MCAs) for menthol cigarettes. This study examined the prospective relationship between behavioral economic demand indices and subjective effects of usual brand menthol cigarettes (UBMC) and preferred MCAs with subsequent performance on a laboratory-based concurrent-choice task comparing UBMC and MCAs. METHODS: Eighty participants who typically smoked menthol cigarettes completed this clinical lab study. After sampling each product, participants completed the cigarette purchase task (CPT) and modified cigarette evaluation questionnaire (mCEQ). Following one-week of substituting their preferred MCA for their UBMC, participants completed a 90-min concurrent-choice self-administration task comparing their UBMC and preferred MCA. Linear regression models explored associations between CPT demand indices and mCEQ subjective effects in the lab with subsequent response effort for UBMCs on the concurrent-choice task. RESULTS: Three demand indices for UBMC were positively associated with UBMC response effort: Essential Value (EV; p=.02), Omax (p=.02), and breakpoint (p=.04). Four CPT demand indices for the preferred MCA significantly corresponded with UBMC response effort: EV (p=.03), Pmax (p=.04), Omax (p=.03), and breakpoint (p=.03). Subjective effects captured by the mCEQ were not associated with response effort. CONCLUSIONS: Demand indices reflecting Persistence (i.e., sensitivity to escalating price) predicted effort to obtain UBMC puffs on the concurrent-choice task. Among this sample, the CPT captured information on the relative reinforcing value (i.e., addiction potential) of combustible tobacco products similar to the longer self-administration task. IMPLICATIONS: In an ever-changing product market, assessing the reinforcing efficacy of menthol cigarettes and putative substitutes quickly and with validity is an important methodological tool for understanding abuse liability. Results suggest that behavioral economic demand indices of cigarette purchase task efficiently capture information on the relative reinforcing value of usual brand menthol cigarettes and plausible alternative tobacco products, similar to a 90-min in-laboratory self-administration task.

Differences in Plasma Fatty Acid Composition Related to Chronic Pancreatitis: A Pilot Study.

OBJECTIVES: Chronic pancreatitis (CP) is an inflammatory disease affecting the absorption of fat-soluble nutrients. Signaling in pancreatic cells that lead to inflammation may be influenced by fatty acids (FAs) through diet and de novo lipogenesis. Here, we investigated the relationship between plasma FA composition in CP with heterogeneity of etiology and complications of CP. MATERIALS AND METHODS: Blood and clinical parameters were collected from subjects with CP (n = 47) and controls (n = 22). Plasma was analyzed for FA composition using gas chromatography and compared between controls and CP and within CP. RESULTS: Palmitic acid increased, and linoleic acid decreased in CP compared with controls. Correlations between age or body mass index and FAs are altered in CP compared with controls. Diabetes, pancreatic calcifications, and substance usage, but not exocrine pancreatic dysfunction, were associated with differences in oleic acid and linoleic acid relative abundance in CP. De novo lipogenesis index was increased in the plasma of subjects with CP compared with controls and in calcific CP compared with noncalcific CP. CONCLUSIONS: Fatty acids that are markers of de novo lipogenesis and linoleic acid are dysregulated in CP depending on the etiology or complication. These results enhance our understanding of CP and highlight potential pathways targeting FAs for treating CP.

The impact of bariatric surgery on admissions for gastrointestinal complications and conditions associated with obesity: A nationwide study.

BACKGROUND: Obesity worsens various gastrointestinal pathologies. While bariatric surgery ameliorates obesity, it substantially modifies the gastrointestinal system depending on surgery type, with limited data on subsequent impact on obesity-related gastrointestinal admissions. METHODS: Using the 2012-2014 Nationwide Readmission Database, we included individuals with obesity who received vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), or hernia repair (HR-control surgery). Our main focus was the adjusted odds ratio (aOR) for gastrointestinal inpatient admissions within 6 months following surgery compared to the 6 months preceding it, while controlling for several confounding factors. Gastrointestinal admissions were grouped into postoperative complications or obesity-associated gastrointestinal conditions. RESULTS: Our cohort included 140,103 adults with RYGB, 132,253 with VSG, and 12,436 HR controls. Postoperative gastrointestinal complications were most common after RYGB, prominently obstruction (aOR = 33.17, 95%CI: 18.01, 61.10), and Clostridium difficile infection (aOR: 12.52, 95%CI: 6.22, 25.19). VSG also saw significantly increased but less frequent similar conditions. Notably, for gastrointestinal conditions associated with obesity, acute pancreatitis risk was higher post-VSG (aOR = 6.26, 95%CI: 4.02, 9.73). Post-RYGB patients were most likely to be admitted for cholelithiasis with cholecystitis (aOR: 4.15, 95% CI: 3.24, 5.31), followed by chronic liver disease (aOR: 3.00, 95% CI: 2.33, 3.87). The risk of noninfectious colitis admissions was threefold higher after RYGB and VSG. No gastrointestinal conditions showed an increase after HR. CONCLUSION: Despite weight loss, bariatric surgery was associated with an increased risk of hepato-pancreatobiliary and colitis admissions related to obesity in the first six postoperative months, with considerable variations in rates of gastrointestinal conditions by surgery type.

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study.

BACKGROUND AND AIMS: Oral nicotine pouches (ONPs) probably offer reduced harm compared with cigarettes, but independent data concerning their misuse liability are lacking. We compared nicotine delivery and craving relief from ONPs with different nicotine concentrations to cigarettes. DESIGN: This was a single-blind, three-visit (≥ 48-hour washout), randomized-cross-over study. Participants were encouraged to complete all study visits in less than 1 month. SETTING: The study took place in Rural/Appalachian Ohio. PARTICIPANTS: Participants comprised 30 adults who smoke cigarettes. Participants (meanage = 34.5) were 60% men and 90% White. INTERVENTION: Participants who were ≥ 12-hour tobacco-abstinent used: (1) a 3-mg nicotine concentration ONP, (2) a 6-mg nicotine concentration ONP and (3) usual brand cigarette in separate visits. ONPs (wintergreen Zyn) were used for 30 minutes; cigarettes were puffed every 30 sec for 5 minutes. MEASUREMENTS: Plasma nicotine and self-reported craving were assessed at t = 0, 5, 15, 30, 60 and 90 minutes. The primary outcome was plasma nicotine concentration at t = 30 minutes. A secondary outcome was craving relief at t = 5 minutes. FINDINGS: At t = 30, mean [95% confidence interval (CI)] plasma nicotine was 9.5 ng/ml (95% CI = 7.1, 11.9 ng/ml) for the 3 mg nicotine ONP, 17.5 ng/ml (95% CI = 13.7, 21.3) for the 6 mg nicotine ONP and 11.4 ng/ml (95% CI = 9.2, 13.6 ng/ml) for the cigarette. Mean plasma nicotine at t = 30 minutes differed between the 3- and 6-mg nicotine ONPs (P = 0.001) and between the 6-mg nicotine ONP and cigarette (P = 0.002). Mean (95% CI) craving at t = 5 minutes was lower for the cigarette (mean = 1.00, 95% CI = 0.61, 1.39) than either the 3 mg (mean = 2.25, 95% CI = 1.68, 2.82; P < 0.0001) or 6 mg nicotine (mean = 2.19, 95% CI = 1.60, 2.79; P < 0.0001) ONP. CONCLUSIONS: Among adult smokers, using 6-mg nicotine concentration oral nicotine pouches (ONPs) was associated with greater plasma nicotine delivery at 30 minutes than 3-mg ONPs or cigarettes, but neither ONP relieved craving symptoms at 5 minutes as strongly as a cigarette. Accelerating the speed of nicotine delivery in ONPs might increase their misuse liability relative to cigarettes.

Identifying Novel Motivation Phase-Specific Cessation Targets for Youth Experiencing Homelessness in the United States.

INTRODUCTION: Of youth experiencing homelessness (YEH; 14-24 years old), 70%+ smoke combustible, commercial tobacco. Though many have tried to quit, most use ineffective methods. Drop-in centers for YEH are opportune places to link YEH to evidence-based treatment. Using the Phase-Based Model (PBM) for Cessation Research, the aim of this study was to identify "Motivation" phase-specific challenges impacting YEH's willingness to make a quit attempt-the goal of this cessation phase. AIMS AND METHODS: Surveys were interview administered with 96 past-week combusted tobacco users accessing drop-in services. Regression models were fit to confirm hypothesized challenges impacting YEH's willingness to quit. RESULTS: Moderate nicotine dependence was noted-a key Motivation phase cessation mechanism targeted-and was associated with population challenges including, but not limited to, replacing food with tobacco, accidental oxygen-deprivation events, and smoking to socialize. While 67.1% of participants made a past-year quit attempt, 45.8% expressed 30-day quit interest. Dimensions of coping with housing were associated with quit attempts and quit interest. Quit attempts were also associated with nicotine dependence, working, and smoking to socialize. Whereas, quit interest was associated with less endorsement of smoking to regulate affect and more endorsement to avoid danger. CONCLUSIONS: Though common challenges targeted in Motivation phase cessation exist among YEH, other challenges may also need to be addressed to promote quitting. IMPLICATIONS: Future research in optimizing evidence-based cessation access for YEH through drop-in centers may consider addressing the challenges of housing, food security, social context, violence, and neurotrauma sequela to bolster YEH willingness to make a quit attempt.

Historical Obesity and Early-Onset Cancers: A Propensity-Weighted Analysis of the National Health and Nutrition Examination Survey.

BACKGROUND: The incidence of early-onset obesity-related cancers (diagnosed < 50 years) is increasing in the U.S. We examined the reported historical body mass index (BMI) of adults with early and later-onset cancers to explore relation to obesity. METHODS: We queried the 1999-2018 NHANES database for adults diagnosed with obesity-related cancers (colorectal, non-colorectal gastrointestinal, uterine, breast). We classified early and late-onset cancer based on a diagnosis age of < 50 and ≥ 50 years, respectively. Propensity-weighted analysis was used to compare prior historical BMIs between the matched groups. RESULTS: After weighing, we included 2,966,528 patients with obesity-related cancers, 846,211 (28%) of which were < 50 years. In the matched analysis, 69.1% of early-onset CRC cases were diagnosed as obese (BMI ≥ 30 kg/m2) before cancer diagnosis, compared to 47.2% of late-onset cases (p < 0.03). Similarly, a higher percentage of adults with other early-onset gastrointestinal cancers had prior obesity as compared to the late-onset cohort (70.3% vs. 40.5%, p = 0.0002). BMI showed a trend toward higher values at ages 20-24 for early-onset CRC and 30-34 for other gastrointestinal cancers. In contrast, later-onset CRC and other gastrointestinal cancers exhibited higher BMI values at later ages (30-34 and 35-39, respectively). Early-onset uterine cancer was linked to a higher BMI compared to later-onset cancer (34.0 vs. 31.1 kg/m2, p < 0.0001), with a trend towards a higher BMI before 19 years old. CONCLUSIONS: Our nationally representative data reveal that higher and earlier body fatness in adulthood associates with early-onset gastrointestinal and uterine cancers. These findings underscore the importance of intensifying efforts to combat early-life obesity.

Substitutability of menthol cigarette alternatives: a clinical trial.

INTRODUCTION: This study assessed the substitutability of plausible combustible menthol cigarette alternatives (MCAs) for usual brand menthol cigarettes (UBMCs) in adults who smoke menthol cigarettes. METHODS: Following three in-lab sampling sessions, 80 adults aged 21-50 who smoke menthol cigarettes chose their preferred MCA: (1) a menthol roll-your-own cigarette (mRYO), (2) a menthol filtered little cigar (mFLC) or (3) a non-menthol cigarette (NMC). Participants were instructed to completely substitute their preferred MCA for their UBMC for 1 week and complete daily diaries documenting adherence and subjective effects. At the final lab visit, participants completed concurrent choice and cross-price elasticity tasks with their substitute product and UBMC as the comparator. RESULTS: Most (65%) participants chose mRYO as their preferred product, followed by NMC and mFLC. Adherence to MCA was high for all products across the week (range: 63%-88%). Positive subjective effects for mRYO decreased over time but remained numerically higher than the other MCA products; craving reduction also decreased for NMC across phases. In the progressive ratio task, participants chose their UBMC in 61.7% of choices; this did not differ by preferred MCA, although the median breakpoint was highest for mRYO and similar for mFLC and NMC. Cross-price elasticity comparing UBMC and the preferred product indicated high substitutability of each MCA at phase 3 (I values -0.70 to -0.82). CONCLUSIONS AND RELEVANCE: mRYOs were the most preferred MCA among the study products, but all MCAs were acceptable substitutes for UBMC using behavioural and economic measures in a short-term trial period.Trial registration number NCT04844762.

The sweet spot study-Developing e-liquid product standards for nicotine form and concentration to improve public health: Protocol for a randomized, double-blinded, crossover study.

OBJECTIVES: E-cigarettes pose significant risks to youth, but smokers may benefit from switching to e-cigarettes by reducing their exposure to toxicants, which creates a challenge for the Food and Drug Administration (FDA) in regulating e-cigarettes to protect population health. This study aims to develop e-liquid product standards for nicotine form and concentration that reduce the appeal of e-cigarettes to young people while keeping e-cigarettes available as a safer alternative for smokers. DESIGN AND PARTICIPANTS: A single-visit, double-blinded, randomized crossover design will be used to examine the effects of e-liquids with varying fractions of free-base nicotine (5%, 25%, 45%, 65%, 85%) among a sample of 66 young adult EC users and 66 older adult smokers, across ecologically valid total nicotine concentrations (20 mg or 50 mg/mL). INTERVENTIONS AND OUTCOMES: A 2-puff session will be conducted to test each of the 10 e-liquids in randomly assigned sequences, followed by a 10-minute washout period and participant ratings on appeal and sensory attributes such as throat hit and harshness, as well as behavioral intentions for continued use. Generalized linear mixed models will be used to determine a free-base nicotine level that has limited or no appeal to young adult e-cigarette users while remaining acceptable to smokers. CONCLUSIONS: This study will provide the FDA with scientific evidence regarding the effect of product standards that mandate a minimum threshold for the fraction of free-base nicotine. TRIAL REGISTRATION: The study is registered on clinicaltrials.gov under the identifier NCT05864586.

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.

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.

Brain Injury Is Prevalent and Precedes Tobacco Use among Youth and Young Adults Experiencing Homelessness.

70%+ of youth and young adults experiencing homelessness (YYEH; 14-24 years old) smoke combustible tobacco. Little is known about the prevalence of acquired brain injury (ABI) among youth and young adult smokers experiencing homelessness (YYSEH) and its impact on tobacco use progression-the aim of our study. Through an interviewer-administered survey, YYSEH were asked about timing of tobacco use; exposure to causes of ABI; including brain oxygen deprivation (BOD; strangulation; accidental; choking games) and blunt force head trauma (BFHT; intentional; shaken violently; accidental); and perpetrators of intentional assault. Participants (n = 96) were on average 22 years old and from populations who experience structural disparities; including those minoritized by race (84.4%) and gender/sexual orientation (26.0%). In total, 87% of participants reported at least one exposure to BFHT and 65% to BOD. Intentional injury was more common than accidental. Furthermore, 60.4% of participants (n = 59) were classified as having ABI using the Brain Injury Severity Assessment. A significant proportion of YYSEH living with ABI were exposed to both BFHT and BOD prior to trying (68.5%, p = 0.002) and to first regular use (82.8%, p < 0.001) of tobacco. Among YYSEH with ABI; injury exposure occurred a median of 1 and 5 years before age of first regular tobacco use, dependent on injury mechanism. ABI from intentional violence is prevalent and precedes tobacco use among YYSEH.

The CARE Health Advocacy Intervention Improves Trauma-Informed Practices at Domestic Violence Service Organizations to Address Brain Injury, Mental Health, and Substance Use.

OBJECTIVE: The aim of this study was to evaluate the impact that domestic violence (DV) service organizations' (SO) agency-wide adoption of CARE had on improving DVSO trauma-informed care (TIC) practices, overall, and in relation to addressing brain injury and mental health. CARE is an advocacy intervention designed to raise DVSOs' capacity to C ONNECT with survivors; A CKNOWLEDGE that head trauma, strangulation, and mental health challenges are common; R ESPOND by accommodating needs in services and providing targeted referrals; and E VALUATE effectiveness of response to meet survivors' stated concerns. We hypothesized that TIC would significantly improve among DVSO staff with the agency's use of CARE. SETTING/PARTICIPANTS/DESIGN: Pre- ( n = 53) and 1-year post-CARE ( n = 60) implementation online surveys were completed by staff at 5 DVSOs in Ohio from 2017 to 2019. MAIN MEASURES: Trauma-Informed Practice Scales (TIPS) were used to assess agency support and overall staff impression of implementing TIC; scales were modified to assess the use of TIC-practices related to head trauma, strangulation, mental health, suicide, and substance use. Attitudes Regarding Trauma-Informed Care (ARTIC-45) subscales assessed DVSO staff's endorsement of personal and organizational support in implementing TIC practices. Response options on the Survivor Defined Practice Scale (SDPS) were modified to gain staff insight into DVSO's ability to facilitate survivor empowerment. Differences in endorsement of TIC practices between pre- and post-CARE implementation were evaluated using regression models. RESULTS: DVSO agency environment ( P < .01) and overall staff impression ( P < .001) regarding implementing TIC practices, and in respect to head trauma ( P < .01), strangulation ( P < .01), mental health ( P < .01), suicide ( P = .04), and substance use ( P < .01), significantly improved with the agency's use of CARE. CARE increased DVSO staff's belief in personal and organizational support to implement TIC ( P < .01 and P = .02, respectively) and in their agency's ability to foster survivor empowerment ( P < .01). CONCLUSION: CARE improved TIC practices of DVSOs, overall, and to address brain injury and mental health.

Changes in Plasma Fatty Acid Abundance Related to Chronic Pancreatitis: A Pilot Study.

Objectives: Chronic pancreatitis (CP) is an inflammatory disease that affects the absorption of nutrients like fats. Molecular signaling in pancreatic cells can be influenced by fatty acids (FAs) and changes in FA abundance could impact CP-associated complications. Here, we investigated FA abundance in CP compared to controls and explored how CP-associated complications and risk factors affect FA abundance. Methods: Blood and clinical parameters were collected from subjects with (n=47) and without CP (n=22). Plasma was analyzed for relative FA abundance using gas chromatography and compared between controls and CP. Changes in FA abundance due to clinical parameters were also assessed in both groups. Results: Decreased relative abundance of polyunsaturated fatty acids (PUFAs) and increased monounsaturated fatty acids (MUFAs) were observed in subjects with CP in a sex-dependent manner. The relative abundance of linoleic acid increased, and oleic acid decreased in CP subjects with exocrine pancreatic dysfunction and a history of substance abuse. Conclusions: Plasma FAs like linoleic acid are dysregulated in CP in a sex-dependent manner. Additionally, risk factors and metabolic dysfunction further dysregulate FA abundance in CP. These results enhance our understanding of CP and highlight potential novel targets and metabolism-related pathways for treating CP.

Physical Activity Delays Obesity-Associated Pancreatic Ductal Adenocarcinoma in Mice and Decreases Inflammation.

BACKGROUND & AIMS: Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), a deadly disease with limited preventive strategies. Lifestyle interventions to decrease obesity might prevent obesity-associated PDAC. Here, we examined whether decreasing obesity by increased physical activity (PA) and/or dietary changes would decrease inflammation in humans and prevent PDAC in mice. METHODS: Circulating inflammatory-associated cytokines of overweight and obese subjects before and after a PA intervention were compared. PDAC pre-clinical models were exposed to PA and/or dietary interventions after obesity-associated cancer initiation. Body composition, tumor progression, growth, fibrosis, inflammation, and transcriptomic changes in the adipose tissue were evaluated. RESULTS: PA decreased the levels of systemic inflammatory cytokines in overweight and obese subjects. PDAC mice on a diet-induced obesity (DIO) and PA intervention, had delayed weight gain, decreased systemic inflammation, lower grade pancreatic intraepithelial neoplasia lesions, reduced PDAC incidence, and increased anti-inflammatory signals in the adipose tissue compared to controls. PA had additional cancer prevention benefits when combined with a non-obesogenic diet after DIO. However, weight loss through PA alone or combined with a dietary intervention did not prevent tumor growth in an orthotopic PDAC model. Adipose-specific targeting of interleukin (IL)-15, an anti-inflammatory cytokine induced by PA in the adipose tissue, slowed PDAC growth. CONCLUSIONS: PA alone or combined with diet-induced weight loss delayed the progression of PDAC and reduced systemic and adipose inflammatory signals. Therefore, obesity management via dietary interventions and/or PA, or modulating weight loss related pathways could prevent obesity-associated PDAC in high-risk obese individuals.

Adherence to Surveillance Endoscopies Posteradication of Barrett's Esophagus With High-grade Dysplasia or Carcinoma In Situ.

GOALS: We aimed to evaluate factors associated with patient adherence to recommended surveillance guidelines during the first 3 years after endoscopic eradication of Barrett's esophagus (BE) with high-grade dysplasia (HGD) or T1a carcinoma in situ (CIS) and the relationship between adherence and detection of recurrence. BACKGROUND: While surveillance endoscopies after treatment of BE with HGD or T1a CIS are an important component of therapy, it is unclear whether these high-risk patients are adhering to recommended surveillance guidelines. MATERIALS AND METHODS: A total of 123 BE patients who underwent radiofrequency ablation±endoscopic mucosal resection for biopsy-proven HGD, or CIS between January 2010 and November 2018 underwent retrospective review for adherence to surveillance guidelines, patient factors related to adherence, and recurrence of dysplasia or CIS at 12, 24, and 36 months. RESULTS: Of 123 BE patients (89 HGD and 34 CIS), adherence during the first year following treatment was 26.97% for HGD patients and 41.18% for CIS patients, with increasing adherence rates in subsequent years. Patients who received 3 to 4 surveillance endoscopies in the first year posttreatment had significantly higher rates of recurrence detection than patients who received 0 to 2 surveillance endoscopies over this interval ( P =0.01). No patient factors were found to impact adherence significantly. CONCLUSIONS: Adherence to recommended surveillance intervals after endoscopic treatment of BE with HGD or CIS is low, with poor adherence during the first year associated with decreased detection of recurrence. Future studies are needed to evaluate risk factors and develop a potential intervention for poor adherence in this high-risk population.

Rising Rates of Severe Obesity in Adults Younger Than 50 Correspond to Rise in Hospitalizations for Non-malignant Gastrointestinal Disease.

BACKGROUND: Colorectal cancer incidence is rising in adults < 50 years old, possibly due to obesity. Non-malignant colorectal conditions are understudied in this population. We hypothesize that developing severe obesity in young adulthood also corresponds with increased hospitalization rates for non-malignant colorectal conditions. METHODS: We examined annual percent change (APC) in the prevalence of obesity in adults < 50 using the 2009-2014 National Health and Nutrition Examination Survey. Using the 2010-2014 Nationwide Readmission Database, we then compared yearly hospitalization trends for various gastrointestinal conditions and their outcomes in adults < 50 with severe obesity vs. no obesity. RESULTS: The prevalence of obesity increased in adults < 50 years in 2009-2014. This increase was most pronounced for severe obesity (APC of + 12.8%). The rate of patients with severe obesity < 50 who were admitted for gastrointestinal diseases has increased by 7.76% per year in 2010-2014 (p < 0.001). This increase was > 10% per year for colorectal conditions such Clostridium difficile infections (APC + 17.3%, p = 0.002), inflammatory bowel disease (APC + 13.1%, p = 0.001), and diverticulitis (APC + 12.7%, p = 0.002). The hospitalization rate for chronic liver diseases and acute pancreatitis also increased by 12.2% and 10.0% per year, respectively (p < 0.01). In contrast, young adults without obesity had lower hospitalization rate for most gastrointestinal diseases. Furthermore, adults with no obesity had lower mortality rates for appendicitis, diverticulitis, pancreatitis and chronic liver diseases than adults with severe obesity. CONCLUSION: Our data suggest that increased adiposity in young adults is associated with more hospitalization and worse outcomes for infectious/inflammatory gastrointestinal conditions. Future prevention strategies are warranted to ameliorate these trends.