Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization.

BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis. METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE. RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways. CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.

Effectiveness of Tofacitinib in Patients With Ulcerative Colitis: A Nationwide Veterans Administration Cohort Study.

INTRODUCTION: There is paucity of data on the effectiveness and safety of tofacitinib among elderly patients with ulcerative colitis (UC). METHODS: Through a retrospective cohort study among the US National Veterans Affairs Healthcare System, we evaluated effectiveness among the elderly (≥65) and young (<65) patients with UC initiated on tofacitinib. RESULTS: Among 158 patients (53 elderly, 105 young), effectiveness at 12 months was 50.94% in the elderly and 33.33% in the young ( P = 0.032). DISCUSSION: In a nationwide cohort of patients with UC initiating tofacitinib, effectiveness was seen in half of the elderly patients.

Incidence of Pneumonia, Related Hospitalization, and Mortality Among Younger Unvaccinated IBD Patients in a Nationwide Cohort.

BACKGROUND AND GOALS: Community Acquired Pneumonia (CAP) is among the most common infections among Inflammatory Bowel Disease (IBD) patients. Our aim was to determine the absolute and relative risk of CAP, related hospitalization, and death among younger (age < 65) unvaccinated IBD patients exposed and unexposed to immunosuppressive medications. MATERIALS AND METHODS: We conducted a retrospective cohort study among a nationwide cohort of younger IBD unvaccinated patients in the VAHS. Exposure was administration of any immunosuppressive medication. The primary outcome was the first occurrence of pneumonia; secondary outcomes being pneumonia related hospitalization and mortality. We reported event rate per 1000 person-years, hazard ratio, and 95% confidence intervals (CIs) for each outcome. RESULTS: Among a total of 26,707 patients, 513 patients developed pneumonia. Mean age in years (SD) was 51.67 (11.34) for the exposed and 45.91 (12.34) for the unexposed group. The overall crude incidence rate was 3.2 per 1000 patient-years (PYs) [4.04/1000 PYs in the exposed versus 1.45/1000 PYs in the unexposed]. The overall crude incidence rates for pneumonia-related-hospitalization and mortality 1.12 and 0.09 per 1000 PYs, respectively. In Cox regression, the exposed group was associated with an increased risk of pneumonia (AHR 2.85; 95% CI: 2.21 to 3.66, P < 0.001) and pneumonia-related-hospitalization (AHR 3.46; 95% CI: 2.20 to 5.43, P < 0.001). CONCLUSIONS: Overall incidence of CAP among younger unvaccinated IBD patients was 3.2 per 1000 PYs. The overall associated hospitalization rates were low, however, higher amongst those exposed to immunosuppressive medications. This data will help patients and physicians make informed decisions regarding pneumococcal vaccine recommendations.

Exogenous Insulin Therapy Is Associated with the Risk of Advanced Colorectal Adenoma in Patients with Diabetes Mellitus.

BACKGROUND/AIMS: Exogenous insulin therapy increases systemic exposure to insulin which may promote the development of colorectal neoplasia. We sought to evaluate the association between exogenous insulin therapy and the incidence of advanced adenoma in type 2 diabetes mellitus. METHODS: A retrospective cohort study was conducted from January 1, 2007, to January 1, 2018, in a regional health system serving the United States Philadelphia metropolitan area, Central New Jersey, and South Central Pennsylvania. Study patients consisted of a random sample of patients with type 2 diabetes mellitus aged 40-80 years who had undergone two rounds of colonoscopy examinations. The exposure was cumulative duration of insulin therapy (i.e., no use, 1-365 days and > 365 days). The outcome was time to incident advanced adenoma. RESULTS: Of the 975 eligible patients, 184 patients accumulated > 365 days of insulin therapy before the follow-up colonoscopy. The mean (standard deviation) duration between the two rounds of colonoscopy examination was 5.1 (2.9) years among the insulin users and 5.3 (3.9) years among non-users. Compared to no insulin exposure, receiving > 365 days of insulin therapy was associated with an increased incidence of advanced adenoma (adjusted hazard ratio [aHR] 4.84, 95% confidence interval [CI] 2.82-8.30), right-sided advanced adenoma (aHR 5.48, 95% CI 2.90-10.35), and 3 or more adenomas (aHR 2.61, 95% CI 1.46-4.69) at the follow-up colonoscopy examination. CONCLUSION: Insulin therapy is associated with an increased risk of advanced adenoma and may serve as a novel risk-stratification factor to enhance the efficiency of existing colorectal cancer screening and surveillance programs.

Development and Validation of Case-Finding Algorithms to Identify Pancreatic Cancer in the Veterans Health Administration.

BACKGROUND: Survival in pancreatic ductal adenocarcinoma (PDAC) remains poor due to late diagnosis. Electronic Health Records (EHRs) can be used to study this rare disease, but validated algorithms to identify PDAC in the United States EHRs do not currently exist. AIMS: To develop and validate an algorithm using Veterans Health Administration (VHA) EHR data for the identification of patients with PDAC. METHODS: We developed two algorithms to identify patients with PDAC in the VHA from 2002 to 2023. The algorithms required diagnosis of exocrine pancreatic cancer in either ≥ 1 or ≥ 2 of the following domains: (i) the VA national cancer registry, (ii) an inpatient encounter, or (iii) an outpatient encounter in an oncology setting. Among individuals identified with ≥ 1 of the above criteria, a random sample of 100 were reviewed by three gastroenterologists to adjudicate PDAC status. We also adjudicated fifty patients not qualifying for either algorithm. These patients died as inpatients and had alkaline phosphatase values within the interquartile range of patients who met ≥ 2 of the above criteria for PDAC. These expert adjudications allowed us to calculate the positive and negative predictive value of the algorithms. RESULTS: Of 10.8 million individuals, 25,533 met ≥ 1 criteria (PPV 83.0%, kappa statistic 0.93) and 13,693 individuals met ≥ 2 criteria (PPV 95.2%, kappa statistic 1.00). The NPV for PDAC was 100%. CONCLUSIONS: An algorithm incorporating readily available EHR data elements to identify patients with PDAC achieved excellent PPV and NPV. This algorithm is likely to enable future epidemiologic studies of PDAC.

A low-voltage alternant direct current electroporation chip for ultrafast releasing the genome DNA of Helicobacter pylori bacterium.

Nucleic acid detection, as an important molecular diagnostic method, is widely used in bacterial identification, disease diagnosis. For detecting the nucleic acid of bacteria, the prerequisite is to release nucleic acids inside the bacteria. The common means to release nucleic acids is the chemical method, which involves complex processes, is time-consuming, and remains chemical inhibitors. Compared with chemical methods, electroporation as a physical method has the advantages of easy operation, short-time consumption, and chemical reagents free. However, the current works using electroporation often necessitates high-frequency or high-voltage conditions, entailing bulky power devices. Herein, we propose a low-voltage alternant direct current (LADC) electroporation chip and the corresponding miniature device for ultrafast releasing the genome DNA from Helicobacter pylori (H. pylori) for detection. We connected a micrometer-interdigital electrode in the chip with a 20 V portable battery to make the miniature device. Using this low-voltage device, our chip released genome DNA of H. pylori within only 5 ms, achieving a cell lysis rate of 99.5%. We further combined this chip with a colorimetric loop-mediated isothermal amplification assay to visually detect H. pylori within ~ 25 min at 10 CFU/µL. We detected 11 clinical samples using the chip, and the detection results were consistent with those of the clinical standard. The results indicate that the LADC electroporation chip is useful for ultrafast release of genome DNA from bacteria and is expected to promote the development of nucleic acid detection in POCT and other scenarios.

Antibiotic Exposure is Associated With a Risk of Esophageal Adenocarcinoma.

BACKGROUND & AIMS: Antibiotic exposure leads to changes in the gut microbiota. Our objective was to evaluate the association between antibiotic exposure and esophageal adenocarcinoma (EAC) risk. METHODS: We performed a nested case-control study using data from the Veterans Health Administration from 2004 through 2020. The case group consisted of patients who received an incident diagnosis of EAC. For each case, up to 20 matched controls were selected using incidence density sampling. Our primary exposure of interest was any oral or intravenous antibiotic use. Our secondary exposures included cumulative number of days of exposure and classification of antibiotics by various subgroups. Conditional logistic regression was used to estimate the crude and adjusted odds ratios (aORs) for the risk of EAC associated with antibiotic exposure. RESULTS: The case-control analysis included 8226 EAC cases and 140,670 matched controls. Exposure to any antibiotic was associated with an aOR for EAC of 1.74 (95% confidence interval [CI], 1.65-1.83) vs no antibiotic exposure. Compared with no antibiotic exposure, the aOR for EAC was 1.63 (95% CI, 1.52-1.74; P < .001) for cumulative exposure to any antibiotic for 1 to 15 days; 1.77 (95% CI, 1.65-1.89; P < 0 .001) for 16 to 47 days; and 1.87 (95% CI, 1.75-2.01; P < .001) for ≥48 days, respectively (P for trend < .001). CONCLUSION: Exposure to any antibiotic is associated with an increased risk of EAC, and this risk increases as the cumulative days of exposure increase. This novel finding is hypothesis-generating for potential mechanisms that may play a role in the development or progression of EAC.

Tumor Differentiation as a Prognostic Marker in Clinically Staged T1bN0 Esophageal Adenocarcinoma.

Current guidelines recommend that clinically staged T1N0 esophageal cancers are to be referred to surgery or endoscopic resection. Using the National Cancer Database, we identified 733 individuals with clinically staged T1N0 esophageal carcinoma, who underwent upfront surgery and did not receive any prior treatment. We assessed upstaging, which was defined as ≥ T2 disease or positive lymph nodes. Poorly differentiated adenocarcinomas were associated with upstaging, whereas squamous cell carcinomas were not. Specifically, the percentage of upstaging among individuals with clinically staged T1b and poorly differentiated tumor was 33.8%. Therefore, clinically staged T1bN0 poorly differentiated esophageal adenocarcinomas are at high risk for upstaging following surgery.

Dopamine agonists and risk of lung cancer in patients with restless legs syndrome.

PURPOSE: To examine the association between long-term use of dopamine agonists (DAs) and the risk of lung cancer in patients with restless legs syndrome (RLS). METHODS: We conducted a retrospective cohort study using Optum Clinformatics® database. We included adults ≥40 years diagnosed with RLS during the study period (1/2006-12/2016). Follow-up started with the first RLS diagnosis and ended on the earliest of: incident diagnosis of lung cancer, end of enrollment in the database or end of the study period. The exposure of interest was cumulative duration of DAs use, measured in a time-varying manner. We constructed a multivariable Cox regression model to estimate HRs and 95% CIs for the association between lung cancer and cumulative durations of DA use, adjusting for potential confounding variables. RESULTS: We identified 295 042 patients with a diagnosis of RLS. The mean age of the cohort was 62.9; 66.6% were women and 82.3% were white. The prevalence of any DA exposure was 40.3%. Compared to the reference group (no use and ≤1 year), the crude HRs for lung cancer were 1.16 (95% CI 0.99-1.36) and 1.14 (95% CI 0.86-1.51) for 1-3 years and >3 years of cumulative DA use, respectively. The adjusted HR for lung cancer was 1.05 (95% CI 0.88-1.25) for 1-3 years and 1.02 (95% CI 0.76-1.37) for >3 years of cumulative DA use, respectively. CONCLUSIONS: At typical doses for the clinical management of RLS, long-term DA use was not associated with risk of lung cancer.

The Non-Invasive Prediction of Colorectal Neoplasia (NIPCON) Study 1995-2022: A Comparison of Guaiac-Based Fecal Occult Blood Test (FOBT) and an Anti-Adenoma Antibody, Adnab-9.

Given the need to improve the sensitivity of non-invasive methods to detect colorectal neoplasia, particularly adenomas, we compared a fecal test using a monoclonal antibody (Mab) raised against constituents of colonic adenomas designated Adnab-9 (Adenoma Antibody 9), recognizing an N-linked 87 kDa glycoprotein, to gFOBT, which is shown to reduce CRC mortality. p87 immunohistochemistry testing is significantly more sensitive (OR 3.64[CI 2.37-5.58]) than gFOBT (guaiac-based fecal occult blood test) for adenomas (<3 in number), advanced adenomas (OR 4.21[CI 2.47-7.15]), or a combination of the two (OR 3.35[CI 2.47-4.53]). p87 immunohistochemistry shows regional Paneth cell (PC) expression mainly in the right-sided colon and is significantly reduced in the ceca of African Americans (p < 0.0001). In a subset of patients, we obtained other body fluids such as urine, colonic effluent, and saliva. Urine tests (organ-specific neoantigen) showed a significant difference for advanced adenomas (p < 0.047). We conclude that fecal p87 testing is more sensitive than gFOBT and Adnab-9 and could be used to better direct the colonoscopy screening effort.

Development of perceptual similarity and discriminability: the perception of Russian phonemes by Chinese learners.

This study explored the perceptual assimilation and discrimination of Russian phonemes by three groups of Chinese listeners with differing Russian learning experience. A perceptual assimilation task (PAT) and a perceptual discrimination test (PDT) were conducted to investigate if/how L1-L2 perceptual similarity would vary as a function of increased learning experience, and the development of assimilation-discrimination relations. The PAT was analyzed via assimilation rates, dispersion K' values, goodness ratings and assimilation patterns. Results revealed an intriguing phenomenon that the perceived Mandarin-Russian similarity first increased from naïve listeners to intermediate learners and then decreased slightly in relatively advanced learners. This suggests that L1-L2 perceptual similarity is subject to learning experience and could follow a potential "rise and fall" developmental pattern. The PDT results were mostly in line with the assimilation-discrimination correspondence with more experience bringing out better discriminability in general. Yet the overall sensitivity d' values from the Chinese groups were relatively low, implying acoustic/articulatory effects on L2 discriminability aside from perceptual assimilation. The results were discussed under the frameworks of L2 Perceptual Assimilation Model, Speech Learning Model and L2 Linguistic Perception Model.

Cost-Effectiveness of a Risk-Tailored Pancreatic Cancer Early Detection Strategy Among Patients With New-Onset Diabetes.

BACKGROUND & AIMS: Screening for pancreatic ductal adenocarcinoma (PDAC) in asymptomatic adults is not recommended, however, patients with new-onset diabetes (NoD) have an 8 times higher risk of PDAC than expected. A novel risk-tailored early detection strategy targeting high-risk NoD patients might improve PDAC prognosis. We sought to evaluate the cost effectiveness of this strategy. METHODS: We compared PDAC early detection strategies targeting NoD individuals age 50 years and older at various minimal predicted PDAC risk thresholds vs standard of care in a Markov state-transition decision model under the health care sector perspective using a lifetime horizon. RESULTS: At a willingness to pay (WTP) threshold of $150,000 per quality-adjusted life-year, the early detection strategy targeting patients with a minimum predicted 3-year PDAC risk of 1% was cost effective (incremental cost-effectiveness ratio, $116,911). At a WTP threshold of $100,000 per quality-adjusted life-year, the early detection strategy at the 2% risk threshold was cost effective (incremental cost-effectiveness ratio, $63,045). The proportion of PDACs detected at local stage, costs of treatment for metastatic PDAC, utilities of local and regional cancers, and sensitivity of screening were the most influential parameters. Probabilistic sensitivity analysis confirmed that at a WTP threshold of $150,000, early detection at the 1.0% risk threshold was favored (30.6%), followed by the 0.5% risk threshold (20.4%) vs standard of care (1.7%). At a WTP threshold of $100,000, early detection at the 1.0% risk threshold was favored (27.3%) followed by the 2.0% risk threshold (22.8%) vs standard of care (2.0%). CONCLUSIONS: A risk-tailored PDAC early detection strategy targeting NoD patients with a minimum predicted 3-year PDAC risk of 1.0% to 2.0% may be cost effective.

Efficacy of Recombinant Zoster Vaccine in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Individuals with inflammatory bowel disease (IBD) have an increased risk of herpes zoster (HZ) infection. Although the efficacy of recombinant zoster vaccine (RZV) is high among immunocompetent individuals, little is known about its effect among immunosuppressed individuals with IBD. METHODS: We conducted a retrospective cohort study among individuals in the national Veterans Affairs Healthcare System diagnosed with IBD on or before January 3, 2018, the earliest date of RZV vaccinations. We collected data on 7008 and 26,292 eligible patients with IBD in the 50- to 60-year and >60-year age groups, respectively. We identified veterans who received RZV and compared the incidence of HZ between vaccinated versus unvaccinated individuals. We performed multivariable Cox regression with time varying analysis to determine the risk of HZ among the vaccinated (full dose and single dose separately) versus unvaccinated cohort, stratified by IBD medications. RESULTS: The crude HZ incidence rate after full dose vaccination of RZV when compared with the unvaccinated group was lower in both the 50- to 60-year age group (0.00 vs 3.93 per 1000 person-years) and >60-year age group (1.80 vs 4.57 per 1000 person-years). RZV vaccination was associated with a significantly lower risk of HZ among the 50- to 60-year and >60-year age groups, although this was limited by low HZ event rates. CONCLUSION: RZV vaccination was associated with decreased risk of HZ infection among both the 50- to 60-year and >60-year age groups. Greater efforts should be made to vaccinate all patients with IBD with RZV.

Development and validation of case-finding algorithms to identify acute pancreatitis in the Veterans Health Administration.

PURPOSE: Acute pancreatitis (AP) is a frequently encountered adverse drug reaction. However, the validity of diagnostic codes for AP is unknown. We aimed to determine the positive predictive value (PPV) of a diagnostic code-based algorithm for identifying patients with AP within the US Veterans Health Administration and evaluate the value of adding readily available structured laboratory information. METHODS: We identified patients with possible AP events first based on the presence of a single hospital discharge ICD-9 or ICD-10 diagnosis of AP (Algorithm 1). We then expanded Algorithm 1 by including relevant laboratory test results (Algorithm 2). Specifically, we considered amylase or lipase serum values obtained between 2 days before admission and the end of the hospitalization. Medical records of a random sample of patients identified by the respective algorithms were reviewed by two separate gastroenterologists to adjudicate AP events. The PPV (95% confidence interval [CI]) for the algorithms were calculated. RESULTS: Algorithm 2, consisting of one ICD-9 or ICD-10 hospital discharge diagnosis of AP and the addition of lipase serum value ≥200 U/L, had a PPV 89.1% (95% CI 83.0%-95.2%), improving from the PPV of algorithm 1 (57.9% [95% CI 46.8-69.0]). CONCLUSIONS: An algorithm consisting of an ICD-9 or ICD-10 diagnosis of AP with a lipase value ≥200 U/L achieved high PPV. This simple algorithm can be readily implemented in any electronic health records (EHR) systems and could be useful for future pharmacoepidemiologic studies on AP.

Prognostic Implications of Tumor Differentiation in Clinical T1N0 Gastric Adenocarcinoma.

BACKGROUND: Current guidelines recommend neoadjuvant chemotherapy in patients with locoregional gastric adenocarcinoma. Patients diagnosed with early stage gastric adenocarcinoma are usually managed with upfront surgical intervention. However, pathologic staging in a subset of these clinically staged patients identifies more advanced locoregional disease requiring adjuvant treatment. Therefore, identifying these patients prior to surgical intervention is critical to ensure employment of the appropriate treatment paradigm. The aim of the current study was to define patient characteristics associated with clinical understaging in early gastric cancer. METHODS: Using the National Cancer Database (2004-2014) we identified 3,892 individuals with clinical T1N0 gastric adenocarcinoma who underwent upfront definitive surgery, had negative surgical margins, and did not receive preoperative chemotherapy or radiotherapy. Patient characteristics were compared between those with pathologic stage T1N0 disease and those who were upstaged upon surgery. RESULTS: Twenty-seven percent of clinical T1N0 gastric adenocarcinomas had a change in stage because of pathologically defined ≥T2 disease or positive lymph nodes. Individuals who were upstaged had a higher tumor grade compared with those with pathologic stage T1N0 disease. Specifically, 41.9% (530/1,264) of individuals with a poorly differentiated tumor were upstaged, compared with only 10.7% (70/656) with a well-differentiated tumor. Approximately 75% of cases involved upstaging because of T misclassification. The highest percentage of upstaging was shown for tumors located at the fundus and body of the stomach. CONCLUSION: Upstaging of clinical T1N0 gastric adenocarcinoma is characterized by higher tumor grade and is mostly a result of a change in T stage. These findings mandate thorough workup in order to identify patients with clinically staged T1N0 disease requiring preoperative chemotherapy. IMPLICATIONS FOR PRACTICE: Upstaging of clinical T1N0 gastric adenocarcinoma is characterized by higher tumor grade and is mostly a result of a change in T stage. These findings mandate thorough workup in order to identify patients with clinically staged T1N0 disease requiring preoperative chemotherapy.

Are Patients With Inflammatory Bowel Disease at an Increased Risk of Developing SARS-CoV-2 than Patients Without Inflammatory Bowel Disease? Results From a Nationwide Veterans' Affairs Cohort Study.

INTRODUCTION: The clinic course of SARS-CoV-2 among patients with inflammatory bowel disease (IBD) has been extensively studied. However, there is a paucity of data on whether patients with IBD have an increased risk of developing SARS-CoV-2 with compared with patients without IBD. METHODS: We conducted a nationwide retrospective cohort study in the US Veterans' Affairs healthcare system from January 1, 2020, to June 30, 2020. We matched each patient with IBD with 2 patients without IBD on age, sex, race, location, and comorbidities. The outcome of interest was development of SARS-CoV-2. RESULTS: Among 38,378 patients with IBD and 67,433 patients without IBD, 87 (0.23%) and 132 (0.20%) patients developed incident SARS-CoV-2 infection, respectively (P = 0.29). DISCUSSION: Patients with IBD are not at a significantly increased risk of developing SARS-CoV-2 infection when compared with patients without IBD.

Incidence of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Patients With Inflammatory Bowel Disease and the Impact of Thiopurines on Their Risk.

INTRODUCTION: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are rare myeloid clonal disorders that commonly affect the elderly population and have poor prognosis. There are limited data on the risk of AML/MDS among patients with inflammatory bowel disease (IBD), especially on the impact of thiopurines (TPs). METHODS: We conducted a retrospective cohort study among patients with IBD from Veteran Affairs data set. The exposure of interest was TP exposure: (i) never exposed to TPs, (ii) past TP use (discontinued >6 months ago), (iii) current TP use with a cumulative exposure of <2 years, and (iv) current TP use with a cumulative exposure of ≥2 years. The outcome of interest was a composite outcome of incident diagnosis of AML and/or MDS. Cox regression was used to estimate the adjusted and unadjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for AML/MDS risk associated with TP use defined as a time-varying exposure. RESULTS: Among 56,314 study patients, 107 developed AML/MDS. The overall incidence of AML/MDS in the IBD population was 18.7 per 100,000 patient-years. The incidences among those never exposed to TPs, past users of TPs, current users of TPs with a cumulative exposure of <2 years, and current users of TPs with a cumulative exposure of ≥2 years were 17.0, 17.7, 30.4, and 30.3 per 100,000 patient-years, respectively. In multivariable Cox regression analysis, compared with never exposed to TPs, current use of TPs was associated with increased risk (adjusted HR 3.05; 95% CI 1.54-6.06, P = 0.0014 for current use of TPs with a cumulative exposure of <2 years and adjusted HR 2.32; 95% CI 1.22-4.41, P = 0.0101 for current use of TPs with a cumulative exposure of ≥2 years), whereas past TP exposure was not. DISCUSSION: Among patients with IBD, current TP use was associated with an increased risk of AML/MDS, which reverts to baseline after discontinuation of TP use.

Digoxin use is associated with pancreatic cancer risk but does not affect survival.

PURPOSE: Digoxin affects several cellular pathways involved in tumorigenesis. We sought to determine the association between digoxin use and pancreatic cancer risk and survival. METHODS: A nested case-control study using The Health Improvement Network (THIN), a population-representative database from the United Kingdom (UK). Cases included all individuals with incident diagnosis of pancreatic cancer. Each case was matched to up to four controls using incidence density sampling based on age, sex, practice site, calendar time, and duration of follow-up. Exposure of interest was digoxin therapy before cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between digoxin use and pancreatic cancer risk were estimated using conditional logistic regression. We further conducted a retrospective cohort study among pancreatic cancer cases using Cox regression model in order to evaluate the association between digoxin use and overall survival. RESULTS: We identified 4,113 cases with incident pancreatic cancer and 16,072 matched controls. The adjusted OR for diagnosis of pancreatic cancer among active digoxin users was 1.41 (95% CI 1.16-1.72). The risk did not change among active users with duration of therapy of more than 1 year (adjusted OR of 1.39, 95% CI 1.11-1.76). Digoxin was not associated with change in overall survival with an adjusted hazard ratio of 0.97 (95% CI 0.81-1.18). CONCLUSIONS: Digoxin use was associated with modestly increased pancreatic cancer risk but did not affect overall survival.

Survival Outcomes Following Lymph Node Biopsy in Thin Melanoma-A Propensity-Matched Analysis.

BACKGROUND: The use of sentinel lymph node biopsy in patients with T1 melanoma ≤ 1 mm has not been reported in a prospective clinical trial setting, so these clinical outcomes remain understudied. This study seeks to evaluate overall survival (OS) with and without lymph node biopsy (LNB) in patients with clinical T1N0M0 melanoma (0.5-1.0 mm). PATIENTS AND METHODS: Patients were identified using the National Cancer Data Base (2004-2012). After stratification into 0.5-0.7-mm and 0.8-1.0-mm groups, patients undergoing LNB were propensity score-matched 1:1 to patients not undergoing LNB. OS was compared using the Kaplan-Meier method and the stratified log-rank test. RESULTS: Resection was performed in 28,846 patients, and LNB in 14,028 (49%); 15,194 were included in propensity score-matched analysis. The LNB and no-LNB groups were well balanced on all studied covariates (standardized mean difference < 0.10). Among patients with tumors 0.5-0.7 mm, 5- and 10-year OS were 94.7% and 82.7%, respectively, for the LNB group compared with 94.3% and 84.4% for the no-LNB group (p = 0.35). Among patients with tumors 0.8-1.0 mm in thickness, 5- and 10-year OS were 93.9% and 81.6%, respectively, for the LNB group compared with 90.3% and 74.3% for the no-LNB group (p < 0.0001). CONCLUSIONS: There was no difference in OS by LNB status in patients with lesions 0.5-0.7 mm, consistently with recommendations against its routine use in this group. In lesions 0.8-1.0 mm, receipt of LNB was associated with a clinically small but significant improvement in OS. Further study is warranted to better understand this outcome difference.