Reagent-Controlled Regiodivergent Annulations of Achmatowicz Products with Vinylogous Nucleophiles: Synthesis of Bicyclic Cyclopenta[b]pyrans and 8-Oxabicyclo[3.2.1]octane Derivatives.

Two reagent-controlled regiodivergent annulation protocols for Achmatowicz products with vinylogous nucleophiles have been developed, which furnished a series of bicyclic cyclopenta[b]pyrans and 8-oxabicyclo[3.2.1]octane derivatives in 28-90% yields. Plausible mechanisms were proposed to involve either Pd-catalyzed Tsuji-Trost allyl-allyl coupling and concomitant Michael cyclization or quinine-promoted cascade stepwise [5 + 2] cycloaddition and intramolecular Michael cyclization.

Bulky Di(1-adamantyl)phosphinous Acid-Ligated Pd(II) Precatalysts for Suzuki Reactions of Unreactive Aryl Chlorides.

Di(1-adamantyl)phosphine oxide (SPO-Ad: Ad2P(V)(=O)H), a stable tautomer of di(1-adamantyl)phosphinous acid (PA-Ad: Ad2P(III)-OH), was employed to synthesize two new PA-Ad-coordinated complexes, POPd-Ad and POPd2-Ad. POPd-Ad was easily transformed from POPd2-Ad in acetonitrile, and the [M - H]- ion of the deprotonated POPd-Ad was observed in the electrospray ionization-mass spectrum of POPd2-Ad. Both complexes are effective precatalysts for the Suzuki reaction of aryl chlorides. The reduction of Pd(II) in POPd-Ad and POPd2-Ad by arylboronic acid was examined, and the ideal Pd-to-PA ratio in the Suzuki reaction was found to be 1:1. The effect of temperature on the catalytic yields was studied to examine the possible ligation state of the active species and the dimer-to-monomer process of POPd2-Ad. Mononuclear and mono-ligated Pd species was assumed to be catalytically active. The electronic and steric effects of PA-Ad were slightly better than those reported for PA-tBu ( t Bu2P(III)-OH). Density functional theory calculations were performed to evaluate the formation of mono-ligated and mononuclear Pd species from POPd-Ad and POPd2-Ad. Furthermore, the reaction time and catalyst loading could be reduced for the reported POPd1-tBu precatalyst using the optimized reaction conditions for POPd-Ad. The complexes synthesized in this extensive study will complement the existing SPO-coordinated POPd series of precatalysts.

Cobalt Iron Oxides Prepared by Acidic Redox-Assisted Precipitation: Characterization, Applications, and New Opportunities.

The microscopic homogeneity of mixed metals in a single-phase oxide is a critical issue in improving material performance. Aqueous alkaline precipitation is the most common approach but it has the limits of microscopic inhomogeneity because of intrinsically different precipitation rates between metal cations. Herein, we demonstrate a new preparation of uniformly structural substituted cobalt iron oxides via acidic redox-assisted precipitation (ARP) upon the interaction of CoII and K2FeO4. This low-pH synthesis features the redox process between Co and Fe, presumably through the formation of inner-sphere complexes such as [(H2O)5CoII-O-FeVIO3]. With the nucleation starting from such complexes, one obtains a product with predominantly mixed-metal Co-O-Fe moieties, which improves the electrical conductivity of the product. This work further analyzes how the properties of the product species evolve during the hydrothermal synthesis step in the ARP process. We see that the Co/Fe ratio slowly increases from about 1:1 to a final value of 2:1, but does not reach the expected redox stoichiometry of 3:1. At the same time, the magnetization also increases, reaching a value of 16.9 emu g-1 for the final superparamagnetic product, which is three times higher than the value of monometallic Co3O4 and Fe2O3. The cobalt iron oxide samples obtained from ARP also possess superior oxygen evolution activity (307 mV overpotential at 10 mA cm-2 µg-1) compared to a mixture of Co3O4 and Fe2O3 (422 mV) or pure cobalt oxide (350 mV), highlighting the structure-induced enhancement of the catalytic activity. The difficult synthesis of evenly blended trinary/quaternary metals in a single-oxide phase may become possible in the future via ARP.

Proton Pump Inhibitor Use is Associated With Risk of Pancreatic Cancer: A Nested Case-Control Study.

PURPOSE: To investigate the use of proton pump inhibitors (PPIs) and the risk of pancreatic cancer. METHODS: A nested case-control analysis was conducted. Patients with pancreas cancer were matched with controls by propensity score. Univariate and multivariate logistic regression models were used to determine whether PPIs use affected the risk of pancreas cancer. Dose effect was analyzed based on the cumulative defined daily dose (DDD), which was calculated using the total supply of PPIs to individual patients in terms of days and quantity. RESULTS: A total of 1087 patients with pancreas cancer were matched with 1087 control patients from the database. The overall adjusted odds ratio (OR) of PPI use associated with pancreas cancer was 1.69 (95% confidence interval [CI], 1.44-2.05). Dose analysis by cumulative DDD, based on all types of PPI combined, revealed a lower adjusted OR of 0.92 (95% CI, 0.64-1.33) for those on <30 cumulative DDD compared with those on ≥150 cumulative DDD, whose adjusted OR was 2.19 (95% CI, 1.68-2.85). Compared with PPI nonusers, the risks of pancreas cancer were: OR 0.89 (95% CI, 0.62-1.27) for patients using PPI <30 days and 2.22 (95% CI, 1.68-2.94) for ≥150 days. CONCLUSIONS: Risk of pancreas cancer was associated with PPI use in patients with peptic ulcer diseases or gastroesophageal reflux disease.

Association Between Cholangiocarcinoma and Proton Pump Inhibitors Use: A Nested Case-Control Study.

Background: The present study aimed to examine the odds of cholangiocarcinoma (CCA) in patients with proton pump inhibitors (PPIs) use. Methods: A nested case-control study design was employed using data obtained from Taiwan's National Health Insurance Research Database. In total, 2,293 patients with confirmed diagnosis of CCA were identified and served as the CCA group. The CCA patients were propensity score-matched with 2,293 subjects without CCA who served as the control group. The cumulative defined daily dose (DDD) of PPIs was calculated based on the total supply in days and quantity of individual PPIs. Univariable and multivariate logistic regression models were used to determine the odds of CCA, and calculated odds ratios (ORs) and 95% confidence intervals (CI) were used to assess PPIs use and odds of CCA. Results: The overall adjusted OR of PPIs use-associated CCA was 2.58 (95% CI 2.27, 2.93). The adjusted OR of CCA by cumulative DDD dose of PPIs and CCA was analyzed and revealed those odds of CCA are associated with all types of PPIs. Conclusions: There were odds of intrahepatic and extrahepatic CCA among PPIs users. All PPIs use was associated with odds of CCA. Analyses of larger numbers of cases are needed to confirm these findings.

Association of Endoscopic Sphincterotomy or Papillary Balloon Dilatation and Biliary Cancer: A Population-Based Cohort Study.

Endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilatation (EPBD) have become the main therapeutic procedures in the treatment of biliary and pancreas disease. The risk of cholangiocarcinoma (CCA) is not well investigated among post-EST/EPBD patients with benign diseases, particularly in Asia population. A retrospective nationwide cohort study using data from Taiwan's National Health Insurance Research Database (from January 1, 1998 through December 31, 2010) was conducted. Among patients with history of biliary stone with cholangitis, there were 17,503 patients in the EST/EPBD cohort and 69,998 subjects in the comparison. The incidence rate ratio was calculated using the Poisson regression model. Multivariable Cox proportional hazard models, adjusted for potential confounding factors, were used to assess the risk of developing CCA associated with endoscopic EST/EPBD. The cumulative incidences of CCA in the 2 cohorts were calculated using Kaplan-Meier analyses, and differences between the survival curves of the 2 cohorts were analyzed using a log-rank test. The overall incidence of CCA in the EST/EPBD cohort was higher than in the controls (1.36 vs 7.37 per 1000 person-years, IRR = 5.40, 95% CI = 5.15-5.67), with an adjusted HR of 4.41 (95% CI = 3.86-5.04). There were no CCA occurrences among patients receiving EST over the follow-up period 3 year after EST performed. The cumulative incidence of extrahepatic CCA seemed to be little growing in patients receiving EPBD. The cumulative incidence of intrahepatic CCA was also steady increasing in patients treated with EPBD and was more than patients receiving EST 10 years after EPBD by Kaplan-Meier analysis. In the population-based cohort study, EST is not associated with a long-term risk of intrahepatic and extrahepatic CCA. The risk of CCA for EPBD needs further investigation.

Risk of liver cirrhosis in patients with tuberculosis: a nationwide cohort study.

BACKGROUND: Most of the previous reports found cirrhosis patients with a high risk of subsequent tuberculosis (TB). However, data about the risk of developing liver cirrhosis in TB patients are limited. As a hepatitis endemic area, the risk of liver cirrhosis in patients with TB should be elucidated in Taiwan. METHODS: We conducted the study using Taiwan's National Health Insurance Research Database. Patients with TB (n = 9339) were identified as the TB cohort and matched with a control (n = 37 356). Each study participant was followed until diagnosis of liver cirrhosis, loss of follow-up, death, withdrawal from the insurance or until 31 December 2011. RESULTS: A cumulative incidence of liver cirrhosis in the TB cohort had a significantly higher risk for liver cirrhosis compared with the control (log-rank test, P < 0·001). The overall incidence of liver cirrhosis was significantly higher in the TB group than in controls [3·83 vs. 2·02 per 1000 person-year; crude hazard ratio (HR) = 1·88; 95% confidence interval (CI) = 1·59-2·23]. After controlling for age, gender and comorbidities, the risk was 1·79-fold (95% CI = 1·50-2·14) higher in the TB group than in the controls. Analysis by Cox proportional hazard regression revealed that TB increased the risk of cirrhosis in patients with either hepatitis B (adjusted HR = 1·91; 95% CI = 1·05-3·47) or hepatitis C (adjusted HR = 2·56; 95% CI = 1·37-4·78). CONCLUSION: An increased incidence of liver cirrhosis was observed among TB patients in Taiwan.

Statins are associated with a reduced risk of cholangiocarcinoma: a population-based case-control study.

AIMS: Cholangiocarcinoma (CCA) is the second most common primary liver cancer in the world. Due to the lack of effective treatments, the survival rate of CCA is low and it is usually considered difficult to diagnose early. To date, no effective strategies for the prevention of CCA have been developed. Statins are cholesterol-lowering agents which possess pleiotropic properties and the use of statins may reduce cancer risk. The aim of the study was to investigate the effect of statin use on the risk of CCA. METHODS: We used nationwide insurance data to perform a case-control study including 3174 CCA patients diagnosed in 2002-2011 and 3174 propensity score matched controls. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated to assess the association between CCA risk and statin use by type of statin and dose. RESULTS: Patients with CCA were slightly younger than controls with mean ages of 67.4 (SD 12.3) and 68.5 (SD 13.2) years (P = 0.001), respectively, and had less users of statins (22.7 vs. 26.5%, P < 0.001). The overall adjusted OR of statin use associated CCA was 0.80 (95% CI 0.71, 0.90) and lowered for those with longer medications. The OR ranged from 0.65 to 0.77. Stronger dose-response association was seen when using lovastatin. CONCLUSIONS: Statin use is associated with reduced risk of CCA and there is a dose-response relationship between the use of statins and risk of CCA.

The relationship between Helicobacter pylori and cancer risk.

OBJECTIVES: This study investigated the correlation between Helicobacter pylori (HP) and cancer risk. We compared the age, sex, and comorbidity of cancer patients both infected and not infected by HP. METHODS: In this study, we compared a comparison cohort (N=24,088) and an HP cohort (N=6022), both taken from the NHI database. We performed a statistical analysis with the multivariable Cox proportional model to estimate the risk of developing cancer for a comparison and the HP cohort. RESULTS: Our results showed that the proportion of peptic ulcers in the HP cohort was nearly 4 times higher than that in the comparison cohort. The HP cohort was significantly associated with increased colorectal (HR=1.73, 95% CI=1.08-2.77), stomach (HR=5.21, 95% CI=2.46-11.05) and pancreatic (HR=2.77, 95% CI=1.04-7.39) cancer risks compared to the comparison cohort. In addition, the cancer risk in the HP cohort was considerably higher than that in the comparison cohort when hypertension was absent in both cohorts. CONCLUSIONS: In this study, we proposed a method to investigate the correlation between HP infection and cancer risk. We found that HP infection is associated with the development of colorectal, stomach, and pancreatic cancers, and could thus be an independent carcinogenic risk factor.