A pilot randomized clinical trial of γ-tocopherol supplementation on wood smoke-induced neutrophilic and eosinophilic airway inflammation.

Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation. Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans. Methods: This was a randomized, placebo-controlled clinical trial testing the effect of a short course of γ-tocopherol-enriched supplementation on airway inflammation following a controlled exposure to wood smoke particulates. Results: Short-course γ-tocopherol intervention did not reduce wood smoke-induced neutrophilic airway inflammation, but it did prevent wood smoke-induced eosinophilic airway inflammation. Conclusion: γ-Tocopherol is a potential intervention for exacerbation of allergic airway inflammation, but further study examining longer dosing periods is required.

New-Onset Diabetes Is a Potential Marker for the Malignant Transformation of Pancreatic Cysts: A Real-World Population Cohort Study.

OBJECTIVES: New-onset diabetes mellitus has been shown to be associated with pancreatic cancer (PC) in the general population. Our objective was to leverage real-world data to assess the association of new-onset diabetes (NODM) with malignant transformation in a large longitudinal cohort of pancreatic cyst patients. METHODS: A retrospective longitudinal cohort study was conducted using IBM's MarketScan claims databases from 2009 to 2017. From 200 million database subjects, we selected patients with newly diagnosed cysts without prior pancreatic pathology. RESULTS: Of the 137,970 patients with a pancreatic cyst, 14,279 had a new diagnosis. Median follow-up was 41.6 months. Patients with NODM progressed to PC at nearly 3 times the rate of patients without a diabetes history (hazard ratio, 2.80; 95% confidence interval, 2.05-3.83) and at a significantly higher rate than patients with preexisting diabetes (hazard ratio, 1.59; 95% confidence interval, 1.14-2.21). The mean interval between NODM and cancer diagnosis was 7.5 months. CONCLUSIONS: Cyst patients who developed NODM progressed to PC at 3 times the rate of nondiabetics and at a greater rate than preexisting diabetics. The diagnosis of NODM preceded cancer detection by several months. These results support the inclusion of diabetes mellitus screening in cyst surveillance algorithms.

Prevalence, Incidence, and Risk of Progression of Asymptomatic Pancreatic Cysts in Large Sample Real-world Data.

OBJECTIVES: Using large-sample, real-world administrative claims data, we evaluated the prevalence of putatively asymptomatic pancreatic cysts, the historical growth in their incident diagnosis, and their risk of malignant progression. METHODS: Data were sourced from IBM MarketScan administrative claims databases of more than 200 million patients. Period prevalence was assessed using 700,000 individuals without conditions that predispose to pancreatic cyst. The standardized cumulative incidence was compared with the cross-sectional abdominal imaging rate from 2010-2017. The risk of progression to pancreatic cancer for 14,279 newly diagnosed patients with a cyst was estimated using Kaplan-Meier analysis. RESULTS: Standardized prevalence increased exponentially with age and was 1.84% (95% confidence interval, 1.80%-1.87%) for patients older than 45. Standardized incidence nearly doubled from 2010-2017 (6.3 to 11.4 per 10,000), whereas the imaging rate changed from only 8.0% to 9.4%. The cumulative risk of pancreatic cancer at 7 years was 3.0% (95% confidence interval, 2.4%-3.5%), increasing linearly (R2 = 0.991) with an annual progression risk of 0.47%. CONCLUSIONS: Using large-sample data, we show a significant burden of asymptomatic pancreatic cysts, with an annual risk of progression to cancer of 0.47% for 7 years. Rapid growth in cyst diagnosis over the last decade far outpaced increases in the imaging rate.

Ischaemic Heart Disease Mortality Increased With Weekend Admission: Results From a Large, Comprehensive Admission Cohort in Australia.

BACKGROUND: The phenomenon of the "weekend effect", whereby patient outcomes are significantly worse for those admitted to hospital on the weekend as compared to weekdays, is well-documented in systematic reviews and meta-analyses in the literature. We sought to assess the effect of the time of a patient's admission on outcomes across an entire cardiology admissions cohort and explore other factors that have been previously identified or proposed to influence these outcomes, including admissions out-of-hours, and patient transfers from other facilities. METHODS: We conducted a retrospective cohort study involving cardiology admissions at a large tertiary referral centre across a 6-year period from 1 January 2012 to 31 December 2017. Outcomes were in-hospital, 30-day and 1-year mortality rates as well as length-of-stay, and readmission rate. 14,078 patients admitted under a cardiologist across the 6-year period were identified, with 3,029 elective patients excluded. Patients were stratified into weekday (n=8,951) or weekend (n=2,098) categories. RESULTS: In-hospital mortality for weekend admissions was noted to be significantly higher compared to weekday admissions (adj OR 1.78, 95% CI 1.40-2.28; p<0.001). Mortality for weekend admissions was also higher at 30-days (adj OR 1.74, 95% CI 1.39-2.17; p<0.001) and at 1-year (adj OR 1.33 95% CI 1.14-1.55; p<0.001). Adjusted for diagnosis, there was a significant increase in in-hospital, 30-day and 1-year mortality seen only for weekend admissions with the final diagnosis of acute myocardial infarction. CONCLUSION: We have identified an association between weekend admissions and higher in-hospital, 30-day and 1-year mortality for the final diagnosis of acute myocardial infarction in our cardiology admissions data over an extended period of time, although confounders cannot be completely discounted. Any steps to reduce the weekend effect need to move to a system where weekend practices are not substantially different to a usual business day. The question of whether changes in organisation practice and the increased costs incurred would reduce mortality in this high-risk group needs to be addressed by further directed research.

New onset diabetes predicts progression of low risk pancreatic mucinous cysts.

BACKGROUND: Patients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts. METHODS: We evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method. RESULTS: The 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5-57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%-20.2%), compared to only 0.8% (95%CI, 0.0%-2.3%) for patients without NODM. Among patients with the largest cysts (20-29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%-89.9%) compared to only 7.5% (95%CI, 1.6%-15.2%) for patients without NODM. CONCLUSION: New onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.

Development of a stratification tool to identify pancreatic intraductal papillary mucinous neoplasms at lowest risk of progression.

BACKGROUND: Because most pancreatic intraductal papillary mucinous neoplasms (IPMNs) will never become malignant, currently advocated long-term surveillance is low-yield for most individuals. AIM: To develop a score chart identifying IPMNs at lowest risk of developing worrisome features or high-risk stigmata. METHODS: We combined prospectively maintained pancreatic cyst surveillance databases of three academic institutions. Patients were included if they had a presumed side-branch IPMN, without worrisome features or high-risk stigmata at baseline (as defined by the 2012 international Fukuoka guidelines), and were followed ≥ 12 months. The endpoint was development of one or more worrisome features or high-risk stigmata during follow-up. We created a multivariable prediction model using Cox-proportional logistic regression analysis and performed an internal-external validation. RESULTS: 875 patients were included. After a mean follow-up of 50 months (range 12-157), 116 (13%) patients developed worrisome features or high-risk stigmata. The final model included cyst size (HR 1.12, 95% CI 1.09-1.15), cyst multifocality (HR 1.49, 95% CI 1.01-2.18), ever having smoked (HR 1.40, 95% CI 0.95-2.04), history of acute pancreatitis (HR 2.07, 95% CI 1.21-3.55), and history of extrapancreatic malignancy (HR 1.34, 95% CI 0.91-1.97). After validation, the model had good discriminative ability (C-statistic 0.72 in the Mayo cohort, 0.71 in the Columbia cohort, 0.64 in the Erasmus cohort). CONCLUSION: In presumed side branch IPMNs without worrisome features or high-risk stigmata at baseline, the Dutch-American Risk stratification Tool (DART-1) successfully identifies pancreatic lesions at low risk of developing worrisome features or high-risk stigmata.

Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection.

PURPOSE: Loss of colonization resistance within the gastrointestinal microbiome facilitates the expansion of pathogens and has been associated with death and infection in select populations. We tested whether gut microbiome features at the time of intensive care unit (ICU) admission predict death or infection. METHODS: This was a prospective cohort study of medical ICU adults. Rectal surveillance swabs were performed at admission, selectively cultured for vancomycin-resistant Enterococcus (VRE), and assessed using 16S rRNA gene sequencing. Patients were followed for 30 days for death or culture-proven bacterial infection. RESULTS: Of 301 patients, 123 (41%) developed culture-proven infections and 76 (25%) died. Fecal biodiversity (Shannon index) did not differ based on death or infection (p = 0.49). The presence of specific pathogens at ICU admission was associated with subsequent infection with the same organism for Escherichia coli, Pseudomonas spp., Klebsiella spp., and Clostridium difficile, and VRE at admission was associated with subsequent Enterococcus infection. In a multivariable model adjusting for severity of illness, VRE colonization and Enterococcus domination (≥ 30% 16S reads) were both associated with death or all-cause infection (aHR 1.46, 95% CI 1.06-2.00 and aHR 1.47, 95% CI 1.00-2.19, respectively); among patients without VRE colonization, Enterococcus domination was associated with excess risk of death or infection (aHR 2.13, 95% CI 1.06-4.29). CONCLUSIONS: Enterococcus status at ICU admission was associated with risk for death or all-cause infection, and rectal carriage of common ICU pathogens predicted specific infections. The gastrointestinal microbiome may have a role in risk stratification and early diagnosis of ICU infections.

Limited usefulness of endoscopic evaluation in patients with continuous-flow left ventricular assist devices and gastrointestinal bleeding.

BACKGROUND: Gastrointestinal bleeding (GIB) is a frequent cause of re-admission in patients with continuous-flow left ventricular assist devices (CF-LVADs) and is associated with multiple endoscopic procedures and high resource utilization. Our aim was to determine the diagnostic and therapeutic yield of endoscopy and to develop a more cost-effective approach for the management of GIB in CF-LVAD recipients. METHODS: We retrospectively reviewed 428 patients implanted with a CF-LVAD between 2009 and 2016 at the Columbia University Medical Center and identified those hospitalized for GIB. Patients were categorized into upper GIB (UGIB), lower GIB (LGIB) and occult GIB (OGIB), based on clinical presentation. RESULTS: Eighty-seven CF-LVAD patients underwent a total of 164 GIBs, resulting in 239 endoscopies. Index presentation was consistent with UGIB in 30 (34.5%), LGIB in 19 (21.8%) and OGIB in 38 (43.7%) patients. On the first GIB, 147 endoscopies localized a bleeding source in 49 (30%), resulting in 24 (16.3%) endoscopic interventions. Of 45 lesions identified, arteriovenous malformations (AVMs) were the most common (22, 48.9%). A gastric or small bowel source (HR 2.8, p = 0.003) and an endoscopic intervention (HR 1.9, p = 0.04) predicted recurrent GIB. The proposed algorithm may reduce the number of endoscopic procedures by 45% and costs by 35%. CONCLUSIONS: Occult GIB is the most common presentation in CF-LVAD patients and carries the lowest diagnostic and therapeutic yield of endoscopy. Performing an intervention was among the strongest predictors of recurrent GIB. Our proposed algorithm may decrease the number of low-yield procedures and improve resource utilization.

Role of Fluorescent In Situ Hybridization, Cholangioscopic Biopsies, and EUS-FNA in the Evaluation of Biliary Strictures.

BACKGROUND AND AIMS: Our goal was to compare the diagnostic accuracy of FISH in the detection of malignancy compared with other standard diagnostic modalities, including brush cytology and biopsy specimens over a 10-year period of prospective data collection. METHODS: We conducted a review of all consecutive biliary strictures evaluated between 2006 and 2016. Patients with a final pathologic diagnosis or conclusive follow-up were included. We evaluated the performance of FISH polysomy (CEP 3, 7, and 17) and 9p21 deletion as well as cholangioscopic biopsy (CBx) and EUS-FNA. Statistical analysis was performed with the Mann-Whitney U and Fisher's exact tests. RESULTS: Of 382 patients with indeterminate strictures, 281 met inclusion criteria. Forty-nine percent were malignant. Cytology, FISH polysomy, and FISH polysomy/9p21 showed a specificity of 99.3%. FISH polysomy/9p21 as a single modality was the most sensitive at 56% (p < 0.001). The sensitivity of FISH polysomy/9p21 and cytology was significantly higher than cytology alone at 63 versus 35% (p < 0.05). EUS-FNA for distal strictures and CBx for proximal strictures increased sensitivity from 33 to 93% (p < 0.001) and 48-76% (p = 0.05) in cytology-negative strictures. CONCLUSIONS: The high specificity of FISH polysomy/9p21 suggests that a positive result is sufficient for diagnosing malignancy in indeterminate strictures. The significantly higher sensitivity of FISH polysomy/9p21 compared to cytology supports the use of FISH in all non-diagnostic cases. Although both EUS-FNA and CBx were complimentary, our results suggest that distal strictures should be evaluated by EUS initially. Proximal strictures may be evaluated by FISH first and then by CBx if inconclusive.

Comparison of the diagnostic accuracy of three current guidelines for the evaluation of asymptomatic pancreatic cystic neoplasms.

Asymptomatic pancreatic cysts are a common clinical problem but only a minority of these cases progress to cancer. Our aim was to compare the accuracy to detect malignancy of the 2015 American Gastroenterological Association (AGA), the 2012 International Consensus/Fukuoka (Fukuoka guidelines [FG]), and the 2010 American College of Radiology (ACR) guidelines.We conducted a retrospective study at 3 referral centers for all patients who underwent resection for an asymptomatic pancreatic cyst between January 2008 and December 2013. We compared the accuracy of 3 guidelines in predicting high-grade dysplasia (HGD) or cancer in resected cysts. We performed logistic regression analyses to examine the association between cyst features and risk of HGD or cancer.A total of 269 patients met inclusion criteria. A total of 228 (84.8%) had a benign diagnosis or low-grade dysplasia on surgical pathology, and 41 patients (15.2%) had either HGD (n = 14) or invasive cancer (n = 27). Of the 41 patients with HGD or cancer on resection, only 3 patients would have met the AGA guideline's indications for resection based on the preoperative cyst characteristics, whereas 30/41 patients would have met the FG criteria for resection and 22/41 patients met the ACR criteria. The sensitivity, specificity, positive predictive value, negative predictive value of HGD, and/or cancer of the AGA guidelines were 7.3%, 88.2%, 10%, and 84.1%, compared to 73.2%, 45.6%, 19.5%, and 90.4% for the FG and 53.7%, 61%, 19.8%, and 88% for the ACR guidelines. In multivariable analysis, cyst size >3 cm, compared to ≤3 cm, (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11, 4.2) and each year increase in age (OR = 1.07, 95% CI = 1.03, 1.11) were positively associated with risk of HGD or cancer on resection.In patients with asymptomatic branch duct-intraductal papillary mucinous neoplasms or mucinous cystic neoplasms who underwent resection, the prevalence rate of HGD or cancer was 15.2%. Using the 2015 AGA criteria for resection would have missed 92.6% of patients with HGD or cancer. The more "inclusive" FG and ACR had a higher sensitivity for HGD or cancer but lower specificity. Given the current deficiencies of these guidelines, it will be important to determine the acceptable rate of false-positives in order to prevent a single true-positive.