History of Cholecystectomy and Risk of Clostridium Difficile Infection.

BACKGROUND: Cholecystectomy affects bile acid physiology. There is growing evidence that both primary and secondary bile acids play a role in the pathogenesis of Clostridium difficile infections (CDIs). AIMS: The aim of this study is to elucidate the relationship and risk of CDI in patients with cholecystectomy. METHODS: We performed a matched cohort study of patients in an integrated healthcare system in Northern California from January 2000 to December 2018. Patients with cholecystectomy (cases, n = 12,617) identified based on Current Procedure Terminology codes were age- and sex-matched to patients without cholecystectomy (controls, n = 37,851). We excluded those with history of CDI at baseline and calculated the hazard ratio (HR) for development of CDI after adjusting for confounders. RESULTS: We found total of 351 incident CDI during average of 4.66 years of follow-up among cases and controls. In multivariate analysis, cholecystectomy was associated with elevated risk of CDI (HR 1.53, 95% confidence interval 1.14-2.04) compared with controls. Stratified analysis shows this effect does not differ according use of proton pump inhibitors (Pinteraction = 0.142), antibiotics (Pinteraction = 0.387), and hospitalization (Pinteraction = 0.252). CONCLUSIONS: Cholecystectomy is associated with mild increased risk of incident CDI, but this effect is not influenced by use of proton pump inhibitors, antibiotics, or hospitalization. Future prospective studies should be conducted to validate these findings and evaluate bile acid changes after a cholecystectomy.

Measures of adiposity are associated with increased risk of peptic ulcer.

BACKGROUND & AIMS: Obesity is associated with systemic inflammation, alterations in the intestinal microbiome, and decreased epithelial integrity. The association between obesity and peptic ulcer has not been investigated thoroughly. METHODS: We conducted a prospective cohort study of 47,120 men enrolled in the Health Professionals Follow-Up Study (mean age at baseline, 54 y). Biennially, we updated information on body mass index (BMI), physical activity, smoking, and use of nonsteroidal anti-inflammatory drugs or aspirin. Self-reported waist and hip measurements were validated among a subsample of participants. Self-reported cases of gastric and duodenal ulcers were confirmed by medical record review. Helicobacter pylori status was determined from endoscopic biopsy specimens, serum antibody measurements, and/or stool antigen assays documented in the medical record. We used Cox proportional hazards modeling to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: We documented 272 gastric and 320 duodenal ulcers over 24 years of follow-up evaluation. The multivariate-adjusted hazard ratio for gastric ulcer was 1.83 (95% CI, 1.20-2.78; P(trend) < .01) for obese men (BMI, ≥30.0 kg/m(2)), compared with men with BMIs of 23.0 to 24.9 kg/m(2), and 1.88 (95% CI, 1.06-3.33; P(trend) = .04) for men with waist-to-hip ratios (WHR) of 1.00 or higher, compared with men with a WHR of 0.85 to 0.89. The risk of duodenal ulcer was not associated with BMI (P(trend) = .24) or WHR (P(trend) = .68). In secondary analyses, increased BMI and WHR each were associated with increased risk of H pylori-negative, but not H pylori-positive, ulcers. The effect of BMI on ulcer risk did not change with use of aspirin or nonsteroidal anti-inflammatory drugs, alcohol consumption, physical activity, or smoking. CONCLUSIONS: In a large prospective cohort of male health professionals, central and total obesity were associated with increased risk of peptic ulcer-particularly gastric and H pylori-negative ulcers.

Trends in Detection of Adenoma and Sessile Serrated Lesions Over a Decade in a Community-Based Healthcare System.

INTRODUCTION: Adenoma detection rate (ADR) is an accepted benchmark for screening colonoscopy. Factors driving ADR and its relationship with sessile serrated lesions detection rate (SSLDR) over time remain unclear. We aim to explore patient, physician, and procedural influences on ADR and SSLDR trends. METHODS: Using a large healthcare system in northern California from January 2010 to December 2020, a total of 146,818 screening colonoscopies performed by 33 endoscopists were included. ADR and SSLDR were calculated over time using natural language processing. Logistic regression was used to calculate the odd ratios of patient demographics, physician attributes, and procedural details over time. RESULTS: Between 2010 and 2020, ADR rose from 19.4% to 44.4%, whereas SSLDR increased from 1.6% to 11.6%. ADR increased by 2.7% per year (95% confidence interval 1.9%-3.4%), and SSLDR increased by 1.0% per year (95% confidence interval 0.8%-1.2%). Higher ADR was associated with older age, male sex, higher body mass index, current smoker, higher comorbidities, and high-risk colonoscopy. By contrast, SSLDR was associated with younger age, female sex, white race, and fewer comorbidities. Patient and procedure characteristics did not significantly change over time ( P -interaction >0.05). Longer years in practice and male physician were associated with lower ADR and SSLDR in 2010, but significantly attenuated over time ( P -interaction <0.05). DISCUSSION: Both ADR and SSLDR have increased over time. Patient and procedure factors did not significantly change over time. Male endoscopist and longer years in practice had lower initial ADR and SSLDR, but significantly lessened over time.

Development of validated sandwich ELISA for detecting peanut allergen Ara h 3 in food.

Peanut is an important food that can cause food allergies, often leading to moderate and severe allergic symptoms such as skin rashes, asthma, and even anaphylactic shock.Research indicates that Ara h 3 is one of the major peanut allergen. In order to establish a simple analytical method for detecting Ara h 3, we developed a sandwich enzyme-linked immunosorbent assay (ELISA) with antibodies that were induced from purified Ara h 3. The experimental results showed that the purified Ara h 3 had good purity, and we successfully prepared capture and detection antibodies. The method established in this study exhibited high specificity and did not cross-react with soybeans, cashew nuts, and sesame. For validation, including precision, recovery and sensitivity were in good condition. We also detected the Ara h 3 in peanut related foods. Overall, the ELISA developed in this study is a reliable method for Ara h 3 detection.

Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study.

BACKGROUND: Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages and portends a poor prognosis. We hypothesized that electronic health records (EHR) could be leveraged to identify individuals at highest risk for GAC from the population seeking routine care. METHODS: This was a retrospective cohort study, with endpoint of GAC incidence as ascertained through linkage to an institutional tumor registry. We utilized 2010 to 2020 data from the Palo Alto Medical Foundation, a large multispecialty practice serving Northern California. The analytic cohort comprised individuals ages 40-75 receiving regular ambulatory care. Variables collected included demographic, medical, pharmaceutical, social, and familial data. Electronic phenotyping was based on rule-based methods. RESULTS: The cohort comprised 316,044 individuals and approximately 2 million person-years (p-y) of observation. 157 incident GACs occurred (incidence 7.9 per 100,000 p-y), of which 102 were non-cardia GACs (incidence 5.1 per 100,000 p-y). In multivariable analysis, male sex [HR: 2.2, 95% confidence interval (CI): 1.6-3.1], older age, Asian race (HR: 2.5, 95% CI: 1.7-3.7), Hispanic ethnicity (HR: 1.9, 95% CI: 1.1-3.3), atrophic gastritis (HR: 4.6, 95% CI: 2.2-9.3), and anemia (HR: 1.9, 95% CI: 1.3-2.6) were associated with GAC risk; use of NSAID was inversely associated (HR: 0.3, 95% CI: 0.2-0.5). Older age, Asian race, Hispanic ethnicity, atrophic gastritis, and anemia were associated with non-cardia GAC. CONCLUSIONS: Routine EHR data can stratify the general population for GAC risk. IMPACT: Such methods may help triage populations for targeted screening efforts, such as upper endoscopy.

Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. RESULTS: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. CONCLUSIONS: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.

Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study.

BACKGROUND: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory but have been linked in some studies to Crohn disease (CD) and ulcerative colitis (UC). OBJECTIVE: To assess the association between aspirin and NSAID use and incident CD and UC. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study I. PATIENTS: 76,795 U.S. women who provided biennially updated data about aspirin and NSAID use. MEASUREMENTS: Incident CD and UC between 1990 and 2008 (outcome) and NSAID and aspirin use (exposure). RESULTS: 123 incident cases of CD and 117 cases of UC occurred over 18 years and 1,295,317 person-years of follow-up. Compared with nonusers, women who used NSAIDs at least 15 days per month seemed to have increased risk for both CD (absolute difference in age-adjusted incidence, 6 cases per 100,000 person-years [95% CI, 0 to 13]; multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56]) and UC (absolute difference, 7 cases per 100,000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87 [CI, 1.16 to 2.99]). Less frequent NSAID use was not clearly associated with risk for CD or UC, and there was no clear association between aspirin use and disease. LIMITATIONS: Cohort participants were exclusively women, most of whom were white. Aspirin and NSAID use were self-reported. CONCLUSION: Frequent use of NSAIDs but not aspirin seemed to be associated with increased absolute incidence of CD and UC. The findings have more mechanistic than clinical implications, because the absolute incidence of CD or UC associated with NSAIDs was low and the increase in risk for CD or UC associated with NSAIDs is unlikely to alter the balance of more common and clinically significant risks and benefits associated with these agents. PRIMARY FUNDING SOURCE: American Gastroenterological Association, IBD Working Group, Broad Medical Research Program, and National Institutes of Health.

Geographical variation and incidence of inflammatory bowel disease among US women.

OBJECTIVE: Geographical variation in the incidence of Crohn's disease (CD) and ulcerative colitis (UC) according to the latitude of residence has been reported in Europe. However, there are no comparable data in the USA. The incidence of CD and UC in relation to latitude was assessed in a geographically diverse population of women enrolled in two large prospective studies in the USA. DESIGN: A prospective study was undertaken of women enrolled in the Nurses' Health Study I (NHS) in 1976 and in the NHS II in 1989. Information on state of residence at the time of birth, at age 15 years and age 30 years was collected in 1992 in NHS I and in 1993 in NHS II. Reported diagnoses of incident CD or UC to the end of 2003 were confirmed by medical record review. Cox proportional hazards models were used to calculate HRs and 95% CIs for risk of CD and UC. RESULTS: In both cohorts, among 175,912 women reporting their residence in 1992, 257 cases of CD and 313 cases of UC were documented over 3,428,376 person-years of follow-up. The incidence of CD and UC increased significantly with increasing latitude (p(trend)<0.01), with residence at age 30 years more strongly associated with risk. Compared with women residing in northern latitudes at age 30, the multivariate-adjusted HR for women residing in southern latitudes was 0.48 (95% CI 0.30 to 0.77) for CD and 0.62 (95% CI 0.42 to 0.90) for UC. The effect of latitude of residence on risk of CD and UC did not vary according to smoking history (p(interaction)=0.26 for CD and 0.99 for UC). CONCLUSION: In a population of US women, increasing latitude of residence was associated with a higher incidence of CD and UC.

The effect of papain hydrolysis on tropomyosin levels in shrimp.

Shrimp allergy is a serious public health problem. Epidemiological studies indicated the main cause of food allergy is the ingestion of shrimp and crab. Consequently, reducing the risk of shrimp and crab allergy is a major research focus. Few studies have demonstrated the effect of enzyme hydrolysis on reduction of shrimp allergens in food. In this study, we used papain, a commonly used enzyme in the food industry, as an ingredient to decrease levels of allergen tropomyosin in shrimp. 0-50U of papain was used to treat the shrimp meat, and then heated to measure the levels of tropomyosin, and determined the change of the protein secondary structure. The results showed that 20U of papain decrease the tropomyosin levels up to 80 %, which was further enhanced when combined with 3 min of heating. Furthermore, the result of Fourier-transform infrared spectroscopy (FTIR) showed alteration of secondary protein structure after the processing. The processing developed in this study may be an effective method used to change the levels and structure of tropomyosin.

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.

Importance: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. Objectives: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. Design, Setting, and Participants: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. Interventions: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. Main Outcomes and Measures: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. Results: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). Conclusions and Relevance: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. Trial Registration: ClinicalTrials.gov identifier: NCT03183141.

Use of aspirin or nonsteroidal anti-inflammatory drugs increases risk for diverticulitis and diverticular bleeding.

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been implicated in diverticular complications. We examined the influence of aspirin and NSAID use on risk of diverticulitis and diverticular bleeding in a large prospective cohort. METHODS: We studied 47,210 US men in the Health Professionals Follow-up Study cohort who were 40-75 years old at baseline in 1986. We assessed use of aspirin, nonaspirin NSAIDs, and other risk factors biennially. We identified men with diverticulitis or diverticular bleeding based on responses to biennial and supplementary questionnaires. RESULTS: We documented 939 cases of diverticulitis and 256 cases of diverticular bleeding during a 22-year period of follow-up evaluation. After adjustment for risk factors, men who used aspirin regularly (≥2 times/wk) had a multivariable hazard ratio (HR) of 1.25 (95% confidence interval [CI], 1.05-1.47) for diverticulitis and a HR of 1.70 (95% CI, 1.21-2.39) for diverticular bleeding, compared with nonusers of aspirin and NSAIDs. Use of aspirin at intermediate doses (2-5.9 standard, 325-mg tablets/wk) and frequency (4-6 days/wk) were associated with the highest risk of bleeding (multivariable HR, 2.32; 95% CI, 1.34-4.02, and multivariable HR, 3.13; 95% CI, 1.82-5.38, respectively). Regular users of nonaspirin NSAIDs also had an increased risk of diverticulitis (multivariable HR, 1.72; 95% CI, 1.40-2.11) and diverticular bleeding (multivariable HR, 1.74; 95% CI, 1.15-2.64), compared with men who denied use of these medications. CONCLUSIONS: Regular use of aspirin or NSAIDs is associated with an increased risk of diverticulitis and diverticular bleeding. Patients at risk of diverticular complications should carefully consider the potential risks and benefits of using these medications.

Clinical and radiologic predictive factors of septic hip arthritis.

OBJECTIVE: The purpose of our study was to identify the clinical and radiologic factors associated with a positive culture during image-guided hip joint aspiration. MATERIALS AND METHODS: We performed a retrospective analysis of 167 consecutive hip aspirations for septic arthritis at a large tertiary medical center. Chart review was performed on the following clinical factors: serum WBC count≥11×10(3)/µL, serum erythrocyte sedimentation rate (ESR)≥20 mm/h, C-reactive protein (CRP)≥100 mg/L, synovial fluid WBC count, synovial fluid polymorphonuclear (PMN) leukocytes≥90%, fever, immunosuppression, antibiotic use, diabetes, presence of a prosthesis, and IV drug use (IVDU). Radiologic studies were reviewed for the following imaging and technical factors: presence of a sinus tract, fluid turbidity, volume of fluid (mL) aspirated, and whether the fluid analyzed was primarily aspirated or reaspirated after lavage. Logistic regression was used to calculate odds ratio (OR) and 95% CI. RESULTS: Of the 167 aspirations, 29 (17.4%) had positive cultures; 6 of 29 (20.7%) positive cultures occurred in reaspirated lavage fluid. On multivariate analysis using logistic regression with stepwise backward elimination, the significant clinical and radiologic predictors were elevated WBC (OR, 4.4; 95% CI, 1.1-17.3), high percentage of synovial fluid PMN leukocytes (OR, 10.6; 95% CI, 2.9-39.8), IVDU (OR, 9.0; 95% CI, 1.3-64.7), and fluid turbidity (OR, 20.5; 95% CI, 6.9-61.4). CONCLUSION: Positive hip cultures are associated with elevated serum WBC, IVDU, high percentage of synovial fluid PMN leukocytes, and fluid aspirate turbidity. Reaspiration of lavage fluid with either nonbacteriostatic saline or contrast material can yield positive cultures.

Impact of nasogastric lavage on outcomes in acute GI bleeding.

BACKGROUND: Nasogastric lavage (NGL) is often performed early in the management of GI bleeding. This practice assumes that NGL results can assist with timely risk stratification and management. OBJECTIVE: We performed a retrospective analysis to test whether NGL is associated with improved process measures and outcomes in GI bleeding. DESIGN: Propensity-matched retrospective analysis. SETTING: University-based Veterans Affairs medical center. PATIENTS: A total of 632 patients admitted with GI bleeding. MAIN OUTCOME MEASUREMENTS: Thirty-day mortality rate, length of hospital stay, transfusion requirements, surgery, and time to endoscopy. RESULTS: Patients receiving NGL were more likely to take nonsteroidal anti-inflammatory drugs and be admitted to intensive care, but less likely to have metastatic disease or tachycardia, be taking warfarin, or present on weekdays. After propensity matching, NGL did not affect mortality (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.37-1.92), length of hospital stay (7.3 vs 8.1 days, P = .57), surgery (OR 1.51; 95% CI, 0.42-5.43), or transfusions (3.2 vs 3.0 units, P = .94). However, NGL was associated with earlier time to endoscopy (hazard ratio 1.49; 95% CI, 1.09-2.04), and bloody aspirates were associated high-risk lesions (OR 2.69; 95% CI, 1.08-6.73). LIMITATIONS: Retrospective design. CONCLUSIONS: Performing NGL is associated with the earlier performance of endoscopy, but does not affect clinical outcomes. Performing NGL at initial triage may promote more timely process of care, but further studies will be needed to confirm these findings.

A prospective, randomized trial of esophageal submucosal tunnel closure with a stent versus no closure to secure a transesophageal natural orifice transluminal endoscopic surgery access site.

BACKGROUND: Secure esophagotomy closure methods are a critical element in the advancement of transesophageal natural orifice transluminal endoscopic surgery (NOTES) procedures. OBJECTIVE: To compare the clinical outcomes in swine receiving an esophageal stent or no stent after a submucosal tunnel NOTES access procedure. DESIGN: Prospective, randomized, controlled trial in 10 Yorkshire swine. SETTING: Academic center. INTERVENTION: An endoscopic mucosectomy device was used to create an esophageal mucosal defect. An endoscope was advanced through a submucosal tunnel into the mediastinum and thorax, and diagnostic mediastinoscopy and thoracoscopy were performed. Ten animals were randomized to no stenting (n = 5) or stenting (n = 5) with a prototype small-intestine submucosa-covered stent. MAIN OUTCOME MEASUREMENTS: Gross and histologic appearance of the mucosectomy and esophagotomy sites as well as clinical outcomes. RESULTS: There was a significant difference in the overall procedure time between the animals that received a stent (35.0 min, range 27-46.0 min) and those with no closure (19.0 min, range 17-32 min) (P value = .018). The unstented group achieved endoscopic and histologic evidence of complete re-epithelialization and healing (100%) at the mucosectomy site compared with the stented group (20%, P = .048). Stent migration into the stomach occurred in two swine. Both groups had complete closure of the submucosal tunnel and well-healed esophagotomy sites. LIMITATIONS: Animal study, small number of subjects. CONCLUSION: The placement of a covered esophageal stent significantly interferes with mucosectomy site healing.

Consensus guidelines in the management of branch duct intraductal papillary mucinous neoplasm: a cost-effectiveness analysis.

BACKGROUND AND AIMS: Based on consensus guidelines, surgical resection of branch duct intraductal papillary mucinous neoplasm (BD-IPMN) is indicated in patients with symptoms of cyst size >or=30 mm, intramural nodules, or dilated main pancreatic duct greater than 6 mm. The aim of this study was to determine the cost effectiveness of consensus guideline implementation in the management of BD-IPMN. METHODS: We developed a decision analytic model to compare the costs and effectiveness of three management strategies for a cohort of 60-year-old patients with branch duct IPMN: (1) surveillance using consensus guidelines for surgical resection (surveillance strategy), (2) surgical resection based on symptoms without surveillance (no surveillance strategy), and (3) immediate surgery (surgery strategy). The primary outcomes were quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed over a wide ranges of estimates. RESULTS: The no surveillance strategy was the least costly, but also the least effective, while the surgery strategy was the most costly and most effective. Compared to the no surveillance strategy, the surveillance strategy cost an additional $20,096 per QALY. The incremental cost-effectiveness ratio of the surgery strategy compared with the surveillance strategy was $132,436 per QALY. In a probabilistic sensitivity analysis, if society was willing to pay $50,000 per quality-adjusted life year gained, then 88.1% of patients using the surveillance strategy would be within budget. CONCLUSIONS: Immediate surgery is the most effective, but may be prohibitively expensive. The surveillance strategy is a cost-effective option compared to no surveillance.

Identification of pyruvate kinase 2 as a possible crab allergen and analysis of allergenic proteins in crabs consumed in Taiwan.

In Taiwan, crab is one of the main causes for food allergy. Several proteins are recognized as crustacean allergens, and tropomyosin is known to be the major one. However, sensitization patterns of Taiwanese patients to crustacean allergens remain unclear. Therefore, we analyzed the specific-IgE binding ability of crucifix crab (Charybdis feriatus) allergens by western blot using patients' sera. In particular, we found a 56 kDa protein in crucifix crab reacted with specific-IgEs in patients' sera, and we further identified the protein as a novel crab allergen pyruvate kinase 2. Additionally, little is known about tropomyosin contents in crabs consumed in Taiwan. Thus, we also quantified the levels of tropomyosin by using enzyme-linked immunosorbent assay (ELISA) among raw and cooked crab species. Our results showed tropomyosin levels varied depending on crab species. In summary, these findings improve the understanding of crustacean allergens and contribute to the clinical diagnosis of crustacean allergies.

Identification of pyruvate kinase as a novel allergen in whiteleg shrimp (Litopenaeus vannamei) by specific-IgE present in patients with shrimp allergy.

Food allergy is one of the most important health issues worldwide. In Taiwan, current literature suggests shrimps and crabs are the most common causes of food allergy, and are frequently associated with acute allergic reactions such as urticaria, atopic dermatitis, and asthma. However, knowledge regarding the shrimp allergens remains limited. Thus, there is an urgent need to establish comprehensive information for elucidating underlying triggers for food allergy. In this study, whiteleg shrimp (Litopenaeus vannamei) was used to evaluate the IgE-binding properties of various shrimp proteins to 7 allergic patients' sera by western blot. A 63 kDa protein was found in raw and cooked shrimp bound to specific-IgEs in 7 and 4 patients' sera, respectively. This protein was further identified as pyruvate kinase based on the proteomic mass spectrometry. This study identifies an important shrimp allergen unique to Taiwan and further testing and prevention measures might be implemented in the allergen analysis.

A prospective study of periodontal disease and risk of gastric and duodenal ulcer in male health professionals.

OBJECTIVES: Periodontal disease has been associated with higher circulating levels of inflammatory markers and conditions associated with chronic inflammation, including vascular disease, diabetes mellitus, and cancer. Limited data exist on the relationship between periodontal disease and gastric and duodenal ulcer. METHODS: We conducted a prospective cohort study of 49,120 men in the Health Professionals Follow-up Study, aged 40-75 years at enrollment in 1986. Biennially, we assessed periodontal disease, tooth loss, and other risk factors for gastric and duodenal ulcer. We validated diagnoses of gastric and duodenal ulcer through medical record review. We used Cox proportional hazards modeling, adjusting for potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 138 cases of gastric ulcer and 124 cases of duodenal ulcer with available information on Helicobacter pylori status over 24 years of follow-up. After adjustment for risk factors, including smoking and regular use of aspirin and non-steroidal anti-inflammatory drugs, men with periodontal disease with bone loss had a multivariate HR of ulcer of 1.62 (95% CI, 1.24-2.12). Periodontal disease appeared to be associated with a similar risk of developing ulcers that were H. pylori negative (HR 1.75; 95% CI, 1.26-2.43) than H. pylori positive (HR 1.40; 95% CI, 0.87-2.24), as well as ulcers in the stomach (HR 1.75; 95% CI, 1.21-2.53) than ulcers in the duodenum (HR 1.47; 95% CI, 0.98-2.19). CONCLUSIONS: Periodontal disease is associated with an increased risk of incident gastric and duodenal ulcer. This relationship may be mediated by alterations in the oral and gastrointestinal microbiome and/or systemic inflammatory factors.

A prospective study of bisphosphonate use and risk of colorectal cancer.

PURPOSE: Bisphosphonates are used for the treatment of bone metastases and have been associated with a lower risk of breast cancer. A recent case-control study showed an inverse association between bisphosphonate use and colorectal cancer. Data from prospective cohorts are lacking. PATIENTS AND METHODS: We prospectively examined the relationship between bisphosphonate use and risk of colorectal cancer among 86,277 women enrolled onto the Nurses Health Study (NHS). Since 1998, participants have returned biennial questionnaires in which they were specifically queried about the regular use of bisphosphonates. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs for risk of colorectal cancer. RESULTS: Through 2008, we documented 801 cases of colorectal cancer over 814,406 person-years of follow-up. The age-adjusted HR for women who regularly used bisphosphonates was 0.92 (95% CI, 0.73 to 1.14) and was further attenuated after adjustment for other risk factors (multivariate HR, 1.04; 95% CI, 0.82 to 1.33). The risk was not influenced by duration of use (P(trend) = 0.79). Compared with nonusers, the multivariate-adjusted HRs of colorectal cancer were 1.24 (95% CI, 0.94 to 1.64) for women with 1 to 2 years of use, 1.16 (95% CI, 0.79 to 1.69) for 3 to 4 years of use, and 0.97 (95% CI, 0.60 to 1.56) for ≥ 5 years of use. There was no association between bisphosphonate use and colorectal cancer within strata of other risk factors. CONCLUSION: In a large prospective cohort, we did not observe an association between long-term use of bisphosphonates and risk of colorectal cancer.

Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study.

OBJECTIVE: To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study, which originally recruited from the 11 most populous states in the US. PARTICIPANTS: 79,899 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008. MAIN OUTCOME MEASURE: Incident hip fracture RESULTS: During 565,786 person years of follow-up, we documented 893 incident hip fractures. The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users. Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher (age adjusted hazard ratio 1.35 (95% confidence interval 1.13 to 1.62)), with longer use associated with increasing risk (P(trend)<0.01). Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use. The relation between PPI use and fracture differed by smoking history (P(interaction)=0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture, with a multivariate hazard ratio for fracture of 1.51 (1.20 to 1.91). In contrast, among women who never smoked there was no association (multivariate hazard ratio 1.06 (0.77 to 1.46)). In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36). CONCLUSION: Chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking.