Association between inflammatory bowel disease and bullous pemphigoid: a population-based case-control study.

The coexistence of inflammatory bowel disease (IBD) and bullous pemphigoid (BP) has been reported. No large-scale study to date has explored the relationship between these diseases. This population-based case-control study examined the association between IBD and BP by using a nationwide database. A total of 5,263 BP patients and 21,052 age- and gender-, hospital visit number-matched controls were identified in the National Health Insurance Research Database of Taiwan (1997-2013). Demographic characteristics and comorbidities including IBD were compared. Logistic regression was conducted to examine the predicting factors for BP. The mean age at diagnosis was 74.88 years and 54.3% of subjects were male. BP patients tended to have more cardiovascular risk factors, autoimmune and neurologic comorbidities, and hematologic cancers than matched controls. There were 20 cases of IBD (0.38%), mostly ulcerative colitis (N = 17, 0.32%) among BP patients, compared to 33 IBD cases (0.16%) among controls (p < 0.001). Ulcerative colitis was found to be significantly associated with BP [adjusted odds ratio (OR) 3.60, 95% confidence interval (CI) 1.91-6.77, p < 0.001] on multivariate analysis. Treatment for IBD was not associated with BP development. Information about diet, lifestyle, alcohol consumption, and smoking habit was not available. We concluded that UC is independently associated with BP.

Association of Daily Aspirin Therapy With Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis C Virus Infection.

BACKGROUND & AIMS: Aspirin therapy has been associated with reduced risk of colon cancer, but there is only limited evidence for its effects on risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We aimed to investigate the association of daily aspirin therapy with HCV-related HCC risk. METHODS: In this cohort study, based on Taiwan's National Health Insurance Research Database, we screened 237,963 patients with chronic HCV infection for the period of 1997 through 2011. We excluded patients with confounding conditions and 2478 patients who continuously received daily aspirin therapy for 90 days or more (treated group) were randomly matched 1:2 with 4956 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores. Cumulative incidence of, and hazard ratio (HR) for, HCC development were analyzed after we adjusted for patient mortality as a competing risk event. RESULTS: The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group over 5 years (4.67%; 95% CI, 3.74%-5.59% vs 7.32%; 95% CI, 6.33%-8.30%; P<.001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.78, 95% CI, 0.64-0.95; P = .011), after adjustment for age per year, male sex, cirrhosis, liver decompensation, hyperlipidemia, statin use, and interferon therapy. Sensitivity subgroup analyses also verified this association (all HRs<1.0). In addition, older age (HR, 1.03 per year; 95% CI, 1.02-1.04), male sex (HR, 1.46; 95% CI, 1.21-1.77), and cirrhosis (HR, 3.13; 95% CI, 2.55-3.84) were independently associated with an increased HCC risk. CONCLUSIONS: In a nationwide cohort study in Taiwan, we found aspirin therapy to be significantly associated with a reduced risk of HCV-related HCC.

Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

Importance: Antiviral therapy cannot erase hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B, and it is not indicated for most hepatitis B virus (HBV) carriers. Another effective way of reducing HCC risk needs to be developed. Aspirin may prevent cancer development, but clinical evidence in patients with HBV-related HCC remains limited. Objective: To investigate the association of daily aspirin therapy with HBV-related HCC risk. Design, Setting, and Participants: In this Taiwan nationwide cohort study, we screened 204 507 patients with chronic hepatitis B for the period January 1, 1997, to December 31, 2012. After excluding patients with confounding conditions, 2123 patients who continuously received daily aspirin for 90 or more days (treated group) were randomly matched 1:4 with 8492 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores, consisting of the follow-up index date, baseline characteristics, and potentially chemopreventive drug use during follow-up. Data were analyzed from August 1 to November 30, 2018. Exposures: Daily aspirin therapy during the study period. Main Outcomes and Measures: Both cumulative incidence of and hazard ratios (HRs) for HCC development were analyzed after adjusting patient mortality as a competing risk event. Results: Of the 10 615 patients included in the analysis, 7690 (72.4%) were men; mean (SD) age was 58.8 (11.8) years. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (5.20%; 95% CI, 4.11%-6.29% vs 7.87%; 95% CI, 7.15%-8.60%; P < .001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Sensitivity subgroup analyses also verified this association (all HRs <1.0). In addition, older age (HR, 1.01 per year; 95% CI, 1.00-1.02), male sex (HR, 1.75; 95% CI, 1.43-2.14), and cirrhosis (HR, 2.89; 95% CI, 2.45-3.40) were independently associated with an increased HCC risk, but nucleos(t)ide analogue (HR, 0.54; 95% CI, 0.41-0.71) or statin (HR, 0.62; 95% CI, 0.42-0.90) use was correlated with a decreased HCC risk. Conclusions and Relevance: Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC.

Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug.

Ultrasound (US) sonication with microbubbles (MBs) has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD) on tumors. Tumors started to receive treatments when they grew up to about 15 mm(3) (early stage) with injection of PLD 10 mg/kg, or up to 50 mm(3) (medium stage) with PLD 6 (or 4) mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue) injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1) US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2) for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3) with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4) for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg), the tumor size still increased for several days and then decreased (a biphasic pattern); (5) MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood vessels and enhances the delivery of PLD into tumors to significantly inhibit tumor growth.

Enhancement of focused ultrasound with microbubbles on the treatments of anticancer nanodrug in mouse tumors.

Ultrasound sonication with microbubbles (MBs) has the potential to enhance the delivery of nanoparticles into the sonicated tumors. In this study, we investigated the feasibility of focused ultrasound (FUS) sonication with MBs to improve nanodrug delivery and tumor treatment. Tumor-bearing mice were first injected with MBs (SonoVue) intravenously, were then sonicated at the tumors with FUS sonication, and were finally injected with the PEGylated liposomal doxorubicin (DOX). The accumulation of DOX in tumors with time, the tumor growth responses for initial treated tumor size and DOX dosage, and the response for an additional sonication after DOX injection were studied. The results demonstrate that FUS sonication with MBs can significantly enhance DOX accumulation in the sonicated tumor at 24 hours after treatment. A significant hindrance to tumor growth is achieved for a small tumor with a low dose, whereas large tumors require a higher dose.