Effects of Aspirin or Clopidogrel on Colorectal Cancer Chemoprevention in Patients with Type 2 Diabetes Mellitus.

Background: The effect of clopidogrel, whose mechanism of action differs from that of aspirin, on CRC risk remains unknown. We investigated the effects of clopidogrel and aspirin, either as monotherapy or combined, on colorectal cancer (CRC) risk in patients with Type 2 diabetes mellitus (T2DM). Methods: We conducted a cohort study using Taiwan National Health Insurance Research Database. Four groups comprising 218,903 patients using aspirin monotherapy, 20,158 patients using clopidogrel monotherapy, 42,779 patients using dual antiplatelet therapy, and 281,840 nonuser matched controls were created using propensity score matching. Cox proportional hazards regression was used to evaluate the CRC risk during follow-up. Results: During the 13-year follow-up period, we found 9431 cases of CRC over 3,409,522 person-years. The overall incidence rates of CRC were 2.04, 3.45, 1.55, and 3.52 per 1000 person-years in the aspirin, clopidogrel, dual antiplatelet, and nonuser cohorts, respectively. The adjusted hazard ratios (aHRs) were 0.59 (95% confidence interval [CI], 0.56-0.61), 0.77 (95% CI, 0.68-0.87), and 0.37 (95% CI, 0.33-0.40) for the aspirin, clopidogrel, and dual antiplatelet cohorts, respectively. Dose- and duration-dependent chemopreventive effects were observed in the three cohorts.

Short-Term Proton Pump Inhibitor Use and Hepatic Encephalopathy Risk in Patients with Decompensated Cirrhosis.

OBJECTIVE: A window period of approximately 3-6 months is usually adopted in studies that evaluate hepatic encephalopathy (HE) risk in proton pump inhibitor (PPI) users. However, HE risk after short-term PPI exposure remains unclear. We explored the effect of short-term PPI exposure using a case-crossover study design. DESIGN: Records of patients with decompensated cirrhosis who had received an HE diagnosis were retrieved from the National Health Insurance Research Database. PPI use rates were compared for case and control with window periods of 7, 14, and 28 days. The adjusted self-matched odds ratio (OR) and 95% confidence interval (CI) from a conditional logistic regression model were used to determine the association between PPI use and HE risk. RESULTS: Overall, 13 195 patients were analyzed. The adjusted OR for HE risk after PPI exposure was 3.13 (95% CI = 2.33-4.20) for the 7-day window, 4.77 (95% CI = 3.81-5.98) for the 14-day window, and 5.60 (95% CI = 4.63-6.78) for the 28-day window. All PPI categories, except omeprazole and pantoprazole, were associated with an increased HE risk. Irrespective of other precipitating factors, such as recent gastrointestinal bleeding or infection, PPI significantly increased HE risk. CONCLUSION: Short-term PPI use is significantly associated with HE in patients with decompensated cirrhosis. Physicians should use PPI in these patients for appropriate indications, and carefully monitor signs of HE even after short-term exposure. Owing to the limitations of retrospective design in the current study, further study is warranted to confirm our findings.

Comparison of mercury and methylmercury bioaccumulation in earthworms (Bimastus parvus) native to landfill-leachate-contaminated forest soil.

Total mercury (THg) and methylmercury (MeHg) bioaccumulation was explored in the Bimastus parvus species of earthworm (B. parvus) native to the leachate-contaminated forest soils around a Hg-polluted traditional landfill in Japan. General soil properties and concentrations of THg and MeHg in forest soils and in B. parvus were determined. The results indicated that the average THg concentrations in B. parvus and in forest soils in the leachate-contaminated sites were 10.21 and 14.90 times higher than those in the reference sites, respectively, whereas similar average MeHg concentrations were observed in forest soils (< 0.01 mg kg-1) and in B. parvus (0.100-0.114 mg kg-1) across all sampled sites. The average bioaccumulation factors of THg in B. parvus (BAFTHg) in forest soil were similar between the leachate-contaminated sites and the reference sites. Cluster and regression analyses demonstrated that the B. parvus Hg (THg and MeHg) and soil THg were positively correlated with each other and with soil organic matter (SOM) and clays, but were negatively correlated with sand and hardly correlated with silts and pH in leachate-contaminated forest soils. From these results, it was proposed that Hg exposure to food chains is possible through B. parvus, because B. parvus showed a high ability to accumulate THg and MeHg in both leachate-contaminated and reference forest soils. Together, these findings indicated that the role of B. parvus in MeHg production is not clear, and it is possible that the MeHg in B. parvus was firstly formed within forest soils and then accumulated in their tissues.

Spatial distribution characteristics of mercury in the soils and native earthworms (Bimastos parvus) of the leachate-contaminated zone around a traditional landfill.

The contents and spatial distribution of mercury (Hg), including soil-Hg fractionation and Hg-containing native earthworm Bimastos parvus (B. parvus) species, were investigated in the leachate-contaminated zone of a large traditional landfill, Japan. Soil-Hg was fractionated into 5 categories: F1/water soluble Hg (Hg-w), F2/human stomach acid soluble Hg (Hg-h), F3/organic-chelated (Hg-o), F4/elemental Hg (Hg-e), and F5/mercuric sulfide (Hg-s). The total mercury (T-Hg) and methylmercury (MeHg) of native B. parvus, and the geochemical properties of soils were examined in this study. Soil T-Hg concentration ranged between 0.227 and 2.919 mg kg-1 dry weight (dw). The T-Hg and MeHg concentrations of B. parvus species ranged from 1.242 to 6.775 mg kg-1 dw and from 0.031 to 0.218 mg kg-1 dw, respectively. Percentages of soil-Hg fractions were in the order of F3/Hg-o > F4/ Hg-e > F5/Hg-s > F1/Hg-w > F2/Hg-h, and the fractions of Hg-o and Hg-e were 55.50% and 35.31%, respectively. Similar distributions and close correlations between the levels of B. parvus Hg and soil Hg-o, Hg-e, and Hg-s were observed in this study. The distribution of Hg in B. parvus was associated with soil organic matter (SOM) content and particle size (sand, clay); however, it was not correlated with Hg-w or Hg-h. The results indicated that easily bioavailable and soluble Hg fractions (Hg-w, Hg-h) of the soil were not appropriate to illustrate the distribution of Hg in native B. parvus. Instead, the stable soil-Hg fractions (Hg-o, Hg-e, and Hg-s) demonstrated good relationships of spatial distribution with B. parvus Hg in leachate-contaminated soil. It is advisable to preclude the evaluation of Hg biological distribution using soluble Hg fractions only. Stable Hg fractions in leachate-contaminated soil should also be included for assessing the biological distribution of Hg in leachate-contaminated soils.

Same-day Versus Split-dose Bowel Preparation Before Colonoscopy: A Meta-analysis.

BACKGROUND: Split-dose regimens (SpDs) were recommended as a first choice for bowel preparation, whereas same-day regimens (SaDs) were recommended as an alternative; however, randomized trials compared them with mixed results. The meta-analysis was aimed at clarifying efficacy level between the 2 regimens. MATERIALS AND METHODS: We used MEDLINE/PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, and Web of Science to identify randomized trials published from 1990 to 2016, comparing SaDs to SpDs in adults. The pooled odds ratios (ORs) were calculated for preparation quality, cecal intubation rate (CIR), adenoma detection rate (ADR), and any other adverse effects. RESULTS: Fourteen trials were included. The proportion of individuals receiving SaDs and SpDs with adequate preparation in the pooled analysis were 79.4% and 81.7%, respectively, with no significant difference [OR=0.92; 95% confidence interval (CI), 0.62-1.36] in 11 trials. Subgroup analysis revealed that the odds of adequate preparation for SaDs with bisacodyl were 2.45 times that for SpDs without bisacodyl (95% CI, 1.45-4.51, in favor of SaDs with bisacodyl). Subjects received SaDs experienced better sleep. CONCLUSIONS: SaDs were comparable with SpDs in terms of bowel cleanliness, CIR, and ADR, and could also outperform SpDs in preparation quality with bisacodyl. SaDs also offered better sleep the previous night than SpDs did, which suggests that SaDs might serve as a superior alternative to SpDs. The heterogenous regimens and measurements likely account for the low rates of optimal bowl preparations in both arms. Further studies are needed to validate these results and determine the optimal purgatives and dosages.

Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus.

Epidemiological evidence reveals that patients with type 2 diabetes mellitus (T2DM) have an increased risk of neurodegenerative diseases (NDs), including dementia and Parkinson's disease (PD). The effects of metformin exposure on dementia and PD risk in patients with T2DM are unknown. We evaluated the effects of metformin exposure on the risk of dementia and PD in patients with T2DM. We performed a cohort study by using Taiwan's National Health Insurance Research Database. We recruited 4651 patients in the metformin cohort and a comparable number of nonmetformin controls by using propensity score matching. Multivariate Cox proportional hazards regression was used to estimate the effects of metformin on the risk of dementia and PD after adjustment for several confounding factors. During the 12-year follow-up, the metformin cohort exhibited a higher risk of PD than the nonmetformin cohort (hazard ratio [HR]: 2.27, 95% confidence interval [CI]=1.68-3.07). The metformin cohort had an increased risk of all-cause dementia (HR: 1.66, 95% CI=1.35-2.04). Moreover, metformin exposure increased the risk of Alzheimer's disease (HR: 2.13, 95% CI=1.20-3.79) and vascular dementia (HR: 2.30, 95% CI=1.25-4.22). The effects of exposure duration and dosage on dementia and PD occurrence were also observed. Long-term metformin exposure in patients with T2DM may lead to the development of NDs, including dementia and PD. Additional large-scale, prospective controlled trials are required to confirm the observed association in patients with T2DM.

Efficacy and Safety of Lamivudine Versus Entecavir for Treating Chronic Hepatitis B Virus-related Acute Exacerbation and Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Oral nucleos(t)ide analogs are recommended for patients with chronic hepatitis B virus (HBV)-related acute exacerbation (AE) and acute-on-chronic liver failure (ACLF). The efficacy and safety of administering entecavir (ETV) and lamivudine (LAM) to such patients remain unclear. METHODS: A comprehensive literature search was performed to select studies published before December 2015 on therapy involving ETV or LAM for chronic HBV-related AE with or without ACLF. The main outcomes were short-term (within 4 mo) and long-term (beyond 4 mo) mortality. The secondary outcomes were virological and biochemical responses, ACLF recurrence, and safety. RESULTS: Three prospective and 8 retrospective cohort studies involving 1491 patients were selected. An overall analysis revealed comparable short-term and long-term mortality rates among all patients who received ETV or LAM [short term: risk ratio (RR)=0.99; 95% confidence interval (CI), 0.78-1.27; long term: RR=0.82; 95% CI, 0.45-1.52]. However, in patients with ACLF, ETV yielded a more favorable long-term outcome than did LAM (RR=0.60; 95% CI, 0.45-0.80). Furthermore, ETV resulted in more efficient virological and biochemical responses than did LAM regarding the HBV DNA undetectable rate (RR=1.34; 95% CI, 1.09-1.63), HBV DNA reduction rate (weighted mean difference=-0.41; 95% CI, -0.69 to -0.13), and serum alanine aminotransferase normalization rate (RR=1.13; 95% CI, 1.05-1.21). CONCLUSIONS: ETV and LAM treatments exerted similar effects on the mortality rate of patients with chronic HBV-related AE with or without ACLF. However, ETV yielded a more favorable long-term outcome than did LAM in patients with ACLF; ETV was associated with greater clinical improvements. Additional larger, long-term randomized controlled trials are required to confirm these conclusions.

Chronic obstructive pulmonary disease is associated with increased recurrent peptic ulcer bleeding risk.

BACKGROUND: The association between chronic obstructive pulmonary disease (COPD) and the risk of recurrent peptic ulcer bleeding (PUB) remains unclear. In this study, we compared the risk of recurrent PUB between patients with and those without COPD. METHODS: Using the Taiwan National Health Insurance Research Database, we first selected patients newly diagnosed with PUB in 2002-2009. Two groups comprising 13,732 COPD cases and 13,732 non-COPD matched controls were created using propensity score matching, thereby making the differences in basic demographics, medication use, and disease conditions between the two groups negligible. Cox proportional hazard regression was used to evaluate the risk of recurrent PUB during the follow-up period. RESULTS: The cumulative recurrence rate of PUB was significantly higher in the patients with COPD than in the non-COPD matched controls (2years: 10.8% vs 9.3%; 6years: 18.3% vs 15.7%, P all <0.05), with an adjusted hazard ratio (HR) of 1.17 (95% confidence interval [CI], 1.08-1.26, P<0.001) and 1.19 (95% CI, 1.12-1.26, P<0.001) within 2-year and 6-year follow-ups, respectively. Patients with COPD using steroids were at a marginally higher risk of recurrent PUB than those who did not use steroids. Multivariate stratified analysis revealed similar results in many subgroups. CONCLUSIONS: The risk of recurrent PUB is higher in patients with COPD than in patients without COPD.

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced dementia risk in patients with diabetes mellitus and hypertension.

OBJECTIVE: The effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) on dementia risk in patients with type 2 diabetes mellitus (DM) and hypertension remain unknown. We investigated the effects of ACEIs and ARBs on dementia risk in patients with type 2 DM and hypertension. METHODS: We conducted a cohort study by using the Taiwan National Health Insurance Research Database. We included 2377 patients receiving ACEIs and 1780 patients receiving ARBs in the ACEI and ARB cohorts, respectively. We included a comparable number of patients not receiving ACEIs and ARBs as controls in the non-ACEI and non-ARB cohorts through propensity score matching. The effect of ACEIs and ARBs on dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors. RESULTS: During the 12-year follow-up period, compared with the non-ACEI cohort, all-cause dementia risk decreased by 26% in the ACEI cohort [hazard ratio (HR)=0.74, 95% confidence interval (CI)=0.56-0.96]. The all-cause dementia risk was nearly 40% lower in the ARB cohort than in the non-ARB cohort (HR=0.60, 95% CI=0.37-0.97). These drugs prevented the occurrence of vascular dementia (VD), however, this effect was nonsignificant for Alzheimer's dementia (AD). Treatment duration- and dosage-related protection effects on dementia occurrence were observed. CONCLUSIONS: ACEIs and ARBs may effectively prevent all-cause dementia, particularly VD, in patients with type 2 DM and hypertension. Moreover, compared with ACEIs, ARBs appear to be more advantageous in dementia prevention.

Nonbismuth concomitant quadruple therapy for Helicobacter pylori eradication in Chinese regions: A meta-analysis of randomized controlled trials.

AIM: To evaluate the applicability of nonbismuth concomitant quadruple therapy for Helicobacter pylori (H. pylori) eradication in Chinese regions. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the efficacy of nonbismuth concomitant quadruple therapy between sequential therapy or triple therapy for H. pylori eradication in Chinese regions. The defined Chinese regions include China, Hong Kong, Taiwan, and Singapore. The primary outcome was the H. pylori eradication rate; the secondary outcome was the compliance with therapy. The PubMed, Embase, Scopus, and Cochrane databases were searched for studies published in the period up to March 2016 with no language restriction. RESULTS: We reviewed six randomized controlled trials and 1616 patients. In 3 trials comparing concomitant quadruple therapy with triple therapy, the H. pylori eradication rate was significantly higher for 7-d nonbismuth concomitant quadruple therapy than for 7-d triple therapy (91.2% vs 77.9%, risk ratio = 1.17, 95%CI: 1.09-1.25). In 3 trials comparing quadruple therapy with sequential therapy, the eradication rate was not significant between groups (86.9% vs 86.0%). However, higher compliance was achieved with concomitant therapy than with sequential therapy. CONCLUSION: The H. pylori eradication rate was higher for nonbismuth concomitant quadruple therapy than for triple therapy. Moreover, higher compliance was achieved with nonbismuth concomitant quadruple therapy than with sequential therapy. Thus, nonbismuth concomitant quadruple therapy should be the first-line treatment in Chinese regions.

Impact of long-term gastric acid suppression on spontaneous bacterial peritonitis in patients with advanced decompensated liver cirrhosis.

OBJECTIVE: Recent studies have presented conflicting results on the association between gastric acid suppression and spontaneous bacterial peritonitis (SBP). The long-term effects of gastric acid suppression on SBP in cirrhotic patients remain unclear. This study evaluated the risk of SBP in advanced decompensated cirrhotic patients with long-term gastric acid suppression. METHODS: Using the Taiwan National Health Insurance Research Database, we identified 4788 patients with decompensated cirrhosis from 1998 to 2011. The SBP incidence rate was compared among proton pump inhibitor (PPI), H2-receptor antagonist (H2RA), and control cohorts. Multivariate Cox proportional hazards regressions analysis was conducted to confirm the association between gastric acid suppression and SBP. RESULTS: Totally, 4788 patients were analyzed: 1870 in the PPI cohort, 1728 in the H2RA cohort, and 1190 in the control cohort. The overall incidences of SBP were 16.8, 11.9, and 9.80 per 1000 person-years in the PPI, H2RA, and control cohorts, respectively. The adjusted hazard ratio (aHR) of SBP during the follow-up period was 1.16- (95% confidence interval [CI], 0.72-1.86) and 1.00-fold (95% CI, 0.63-1.57) higher in the PPI and H2RA cohorts, respectively, than in the control cohort; the result was non-significant. Compared with the control cohort, patients with >180days of PPI therapy had significantly higher risks of SBP, with an aHR of 2.28 (95% CI, 1.37-3.78). CONCLUSIONS: Long-term PPI use is associated with a high risk of SBP in advanced decompensated cirrhotic patients. Well-designed prospective studies are necessary to evaluate the safety of long-term PPI use in such patients.

Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: Obstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepiness (EDS), and sympathetic hyperactivation. Continuous positive airway pressure is the first-line treatment for OSA. However, some patients may have residual EDS. Modafinil and its R-enantiomer, armodafinil, are wakefulness-promoting agents known to be effective in alleviating sleepiness. METHODS: We performed a systematic review and meta-analysis of data from published randomized controlled trials (RCTs) that evaluated the efficacy of modafinil and armodafinil in treating EDS in patients with OSA. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on OSA published before October 2015. FINDINGS: We identified 11 RCTs of modafinil involving 723 patients and 5 RCTs of armodafinil involving 1009 patients. A pooled estimate of the mean differences in sleepiness parameters versus placebo were calculated using the random-effects model. Epworth Sleepiness Scale scores improved significantly in the modafinil group (weighted mean difference [WMD], -2.96 [95% confidence interval (CI), -3.73 to -2.19]) and in the armodafinil group (WMD, -2.63; 95% CI, -3.4 to -1.85) compared with those in the placebo group. Sleep latency, as measured on the Maintenance of Wakefulness Test, was significantly prolonged in the modafinil group (WMD, 2.51 [95% CI, 1.5-3.52]) and in the armodafinil group (WMD, 2.71 [95% CI, 0.04-5.37]). Patients tolerated the adverse events with both medications well. IMPLICATIONS: The findings from our study suggest that both modafinil and armodafinil significantly improved subjective and objective daytime sleepiness. Thus, modafinil and armodafinil may be recommended to patients with OSA, particularly those with EDS.

Intravenous immunoglobulin for postpolio syndrome: a systematic review and meta-analysis.

BACKGROUND: Postpolio syndrome (PPS) is characterized by progressive disabilities that develop decades after prior paralytic poliomyelitis. Because chronic inflammation may be the process underlying the development of PPS, immunomodulatory management, such as intravenous immunoglobulin (IVIg) administration, may be beneficial. METHODS: We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of IVIg in managing PPS. Electronic databases, including PubMed, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials, were searched for articles on PPS published before December 2014. The primary outcomes were pain severity, fatigue scores, and muscle strength. The secondary outcomes were physical performance, quality of life (QoL), and cytokine expression levels. RESULTS: We identified 3 RCTs involving 241 patients and 5 prospective studies involving 267 patients. The meta-analysis of pain severity (weighted mean difference [WMD] = -1.02, 95% confidence interval [CI] = -2.51 to 0.47), fatigue scores (WMD = 0.28, 95% CI -0.56 to 1.12), and muscle strength revealed no significant differences between the IVIg and the placebo group. Regarding QoL, the RCTs yielded controversial outcomes, with improvement in only certain domains of the Short Form 36 (SF-36). Moreover, one prospective study reported significant improvement on SF-36, particularly in patients aged younger than 65 years, those with paresis of the lower limbs, and high pain intensity. CONCLUSION: The present review indicated that IVIg is unlikely to produce significant improvements in pain, fatigue, or muscle strength. Thus, routinely administering IVIg to patients with PPS is not recommended based on RCTs. However, a potential effect in younger patients with lower limbs weakness and intense pain requires confirmation from further well-structured trials.

Hypertension is an important predictor of recurrent colorectal adenoma after screening colonoscopy with adenoma polypectomy.

BACKGROUND: The predictors of recurrent colorectal adenoma have not been fully examined. This study aimed to evaluate the predictors of recurrent colorectal adenoma after initial screening colonoscopy with adenoma polypectomy. METHODS: A retrospective cohort study was conducted at the Taipei Veterans General Hospital from 2003 to 2011. After screening, 356 patients who had undergone two consecutive colonoscopies with colorectal adenoma polypectomy at the initial colonoscopy were enrolled. The recurrence group was patients with recurrent colorectal adenoma at the second colonoscopy, whereas the nonrecurrence group was patients without recurrence. Anthropometric data, biochemical tests, metabolic comorbidities, and adenoma characteristics at initial colonoscopy were compared between the two groups. Cox proportional hazard regression analysis was conducted to identify the predictors of recurrent colorectal adenoma. RESULTS: During a mean follow-up interval of 3.07 ± 1.42 years, 94 patients (26.4%) were in the recurrence group, 262 patients (73.6%) were in the nonrecurrence group. The recurrence group was older, had a wider waist circumference, higher levels of serum alanine aminotransferase (ALT) and triglyceride, a higher prevalence of smoking, nonalcoholic fatty liver disease, metabolic syndrome, and hypertension, and a higher occurrence of initial multiply-located adenomas when compared with the nonrecurrence group (p < 0.05). Cox regression analysis showed that hypertension, smoking, higher ALT level (>40 IU/mL), and multiply-located adenomas were independent predictors for recurrent colorectal adenoma. The risk of recurrent adenoma increased when hypertension was combined with smoking, high ALT level, or multiply-located adenomas. CONCLUSION: Hypertension is an important predictor for recurrent colorectal adenoma after screening colonoscopy with polypectomy.

Different peptic ulcer bleeding risk in chronic kidney disease and end-stage renal disease patients receiving different dialysis.

BACKGROUND: End stage renal disease (ESRD) patients receiving hemodialysis (HD) have a higher risk of peptic ulcer bleeding (PUB). AIMS: Whether ESRD patients receiving peritoneal dialysis (PD) also carries a higher risk of PUB has not been studied. METHODS: This was a cohort study using Taiwan's National Health Insurance research database, whereby 11,408 patients, including 2,239 PD, 2,328 HD, 2,267 chronic kidney disease (CKD) and 4,574 controls with age-sex matching were recruited. The log-rank test was used to analyze differences in accumulated PUB-free survival rates between groups. Cox proportional hazard regression was performed to evaluate independent risk factors for PUB in all the enrollees. RESULTS: During the 7-year follow-up, PD and CKD patients had a significantly higher rate of PUB than matched controls. The risk of PUB between PD and CKD was not significantly different. Moreover, patients receiving HD carried a higher risk of PUB than those receiving PD, with CKD and controls (p all <0.05, by log-rank test). Cox proportional hazard regression analysis showed that CKD (HR 3.99, 95 % CI 2.24-7.13), PD (HR 3.71, 95 % CI 2.00-6.87) and HD (HR 11.96, 95 % CI 7.04-20.31) were independently associated with an increased risk of PUB. Being elderly, male, having hypertension, diabetes, cirrhosis, and nonsteroidal anti-inflammatory drugs and steroid use were other independent risk factors of PUB in all enrollees. CONCLUSIONS: Patients with CKD and ESRD receiving PD or HD carried a higher risk for PUB. They should be screened for risk factors for PUB and receive some protective measures to prevent PUB.

The diminished expression of proangiogenic growth factors and their receptors in gastric ulcers of cirrhotic patients.

OBJECTIVES: The pathogenesis of the higher occurrence of peptic ulcer disease in cirrhotic patients is complex. Platelets can stimulate angiogenesis and promote gastric ulcer healing. We compared the expressions of proangiogenic growth factors and their receptors in the gastric ulcer margin between cirrhotic patients with thrombocytopenia and those of non-cirrhotic patients to elucidate possible mechanisms. METHODS: Eligible cirrhotic patients (n = 55) and non-cirrhotic patients (n = 55) who had gastric ulcers were enrolled. Mucosa from the gastric ulcer margin and non-ulcer areas were sampled and the mRNA expressions of the proangiogenic growth factors (vascular endothelial growth factor [VEGF], platelet derived growth factor [PDGF], basic fibroblast growth factor [bFGF]) and their receptors (VEGFR1, VEGFR2, PDGFRA, PDGFRB, FGFR1, FGFR2) were measured and compared. Platelet count and the expressions of these growth factors and their receptors were correlated with each other. RESULTS: The two groups were comparable in terms of gender, ulcer size and infection rate of Helicobacter pylori. However, the cirrhotic group were younger in age, had a lower platelet count than those in the non-cirrhotic group (p<0.05). The cirrhotic patients had diminished mRNA expressions of PDGFB, VEGFR2, FGFR1, and FGFR2 in gastric ulcer margin when compared with those of the non-cirrhotic patients (p<0.05). Diminished expressions of PDGFB and VEGFR2, FGFR1, and FGFR2 were well correlated with the degree of thrombocytopenia in these cirrhotic patients (ρ>0.5, p<0.001). CONCLUSIONS: Our findings implied that diminished activity of proangiogenic factors and their receptors may contribute to the pathogenesis of gastric ulcers in cirrhotic patients.

Nonpeptic ulcer, nonvariceal gastrointestinal bleeding in hemodialysis patients.

OBJECTIVES: Hemodialysis patients carry a higher risk of peptic ulcer bleeding. Whether hemodialysis patients also have a higher occurrence of nonpeptic ulcer, nonvariceal gastrointestinal bleeding needs further evaluation. METHODS: Using Taiwan's National Health Insurance research database, the occurrence of nonpeptic ulcer, nonvariceal gastrointestinal bleeding was compared among the hemodialysis patients, chronic kidney disease patients, and controls using log-rank test. Risk factors were identified by Cox regression analysis. RESULTS: A total of 20,830 patients were enrolled, including 8210 hemodialysis and 4190 chronic kidney disease patients and 8430 age- and sex-matched controls in a 2:1:2 ratio. In the 7-year follow-up period, hemodialysis patients had a significantly higher cumulative hazard of nonpeptic ulcer, nonvariceal gastrointestinal bleeding than chronic kidney disease patients and controls (P <.001, by log-rank test). The hazard also was significantly higher in the chronic kidney disease patients than in controls. Cox regression analysis revealed that older age, the comorbidities of diabetes mellitus, cirrhosis, and chronic obstructive pulmonary disease, history of uncomplicated peptic ulcer disease, chronic kidney disease (hazard ratio 5.17), hemodialysis (hazard ratio 9.43), and use of selective serotonin reuptake inhibitors were independent risk factors for nonpeptic ulcer, nonvariceal gastrointestinal bleeding in all study patients. Old age, diabetes mellitus, cirrhosis, chronic obstructive pulmonary disease, history of uncomplicated peptic ulcer disease, and use of selective serotonin reuptake inhibitors were independent risk factors in hemodialysis patients. CONCLUSIONS: There is a higher risk of developing nonpeptic ulcer, nonvariceal gastrointestinal bleeding in hemodialysis patients after adjustments for age, sex, underlying comorbidities, and ulcerogenic medication. The risk has increased since patients had chronic kidney disease.

Risk factors for upper gastrointestinal bleeding in coronary artery disease patients receiving both aspirin and clopidogrel.

BACKGROUND: Dual therapy (aspirin and clopidogrel) increases the risk of upper gastrointestinal bleeding (UGIB). Acute coronary syndrome (ACS), a critical ill condition, may increase the risk of UGIB due to stress-related mucosal disease and the impact of receiving dual antiplatelet agents. We identified risk factors of UGIB in patients with coronary artery disease (CAD) receiving dual therapy. METHODS: Patients who received dual therapy due to ACS or postpercutaneous coronary intervention (elective, primary, or urgent) were enrolled retrospectively. We assessed the occurrence of UGIB and identified the risk factors for UGIB at early stage (dual therapy ≤ 2 weeks) and late stage (> 2 weeks) by Cox regression analysis. RESULTS: During a mean follow-up period of 125 days, 67 (12.5 %) out of 534 patients developed UGIB (32 patients at early stage, 35 patients at late stage). Cox regression analysis showed that use of proton pump inhibitor therapy has a protective role in these patients [hazard ratio (HR): 0.10, 95% confidence interval (CI): 0.01-0.71]. ACS (HR: 2.67, 95% CI: 1.33-5.34) has a high risk of developing UGIB at an early stage. Old age (>75 years of age) (HR: 2.13, 95% CI: 1.02-4.47) and prior history of peptic ulcer disease (HR: 3.27, 95% CI: 1.28-8.34) each have an associated high risk for developing UGIB at a late stage. The use of mechanical ventilation (HR: 5.85, 95% CI: 2.19-15.58) also increased UGIB risk at both the early and late stages. CONCLUSION: ACS and mechanical ventilation are important risk factors of UGIB at the early stage (≤ 2 weeks). Additionally, old age (>75 years), past peptic ulcer disease history, and the use of mechanical ventilation play important roles in the occurrence of UGIB at late stage (>2 weeks). However, it was also noted that use of PPI plays a protective role in patients with CAD receiving aspirin and clopidogrel therapy.

Incidence of bleeding from gastroduodenal ulcers in patients with end-stage renal disease receiving hemodialysis.

BACKGROUND: Few large population-based studies have compared the incidence of bleeding of gastroduodenal ulcers between patients with and without end-stage renal disease. We investigated the association between ulcer bleeding and end-stage renal disease in patients receiving hemodialysis, and we sought to identify risk factors for ulcer bleeding. METHODS: We performed a nationwide seven-year population study using data from the National Health Insurance Research Database in Taiwan. We identified 36 474 patients with end-stage renal disease who were receiving hemodialysis, 6320 patients with chronic kidney disease and 36 034 controls matched for age, sex and medication use. We performed log-rank testing to analyze differences in survival time without ulcer bleeding among the three groups. We performed Cox proportional hazard regressions to evaluate the risk factors for ulcer bleeding among the three groups and to identify risk factors in patients receiving hemodialysis. RESULTS: Patients receiving hemodialysis and those with chronic kidney disease had a significantly higher incidence of ulcer bleeding than controls had (p<0.001). Hemodialysis (hazard ratio [HR] 5.24, 95% confidence interval [CI] 4.67-5.86) and chronic kidney disease (HR 1.95, 95% CI 1.62-2.35) were independently associated with an increased risk of ulcer bleeding. Diabetes mellitus, coronary artery disease, cirrhosis and use of nonsteroidal anti-inflammatory drugs were risk factors for ulcer bleeding in patients with end-stage renal disease who were receiving hemodialysis INTERPRETATION: Patients with end-stage renal disease who are receiving hemodialysis had a high risk of ulcer bleeding. Diabetes mellitus, coronary artery disease, cirrhosis and the use of nonsteroidal anti-inflammatory drugs were important risk factors for ulcer bleeding in these patients.

Effect of regression of enlarged neck lymph nodes on radiation doses received by parotid glands during intensity-modulated radiotherapy for head and neck cancer.

OBJECTIVES: The regression of enlarged neck lymph nodes during intensity-modulated radiotherapy (IMRT) may increase actual radiation doses to the parotid glands of patients with head-and-neck cancer. We investigated the changes in the lymph nodes volume during IMRT and the effect of these changes to the parotid gland doses. METHODS: Ten head and neck cancer patients with enlarged neck lymph nodes were enrolled in this study. Computed tomography (CT) imaging was repeated to evaluate the change in lymph nodes volume after initial 45 Gy, and the second part of IMRT (21 Gy) was then replanned to reflect the change of nodal tumor volume. The dosimetric benefit of parotid sparing with replanning was compared with that of no replanning. RESULTS: The enlarged neck lymph nodes in all patients pushed the parotid glands outward in pretreatment CT images. After 45 Gy of IMRT, nodal regression caused the parotid glands to shift inward into the high-dose area. When compared with those without replanning, we found modification of IMRT plan after 45 Gy significantly reduced radiation dose to parotid glands (mean reduction of 2.95 +/- 1.10 Gy to the left and 3.23 +/- 1.37 Gy to the right, respectively; P < 0.001). CONCLUSIONS: Excessive parotid gland doses secondary to the regression of enlarged neck nodes could be mitigated by replanning after 45 Gy. However, recontouring of large lymph nodes that regress during therapy has a risk of under-dosing extracapsular extension of lymph node metastases. Therefore, recontouring should be done with extreme caution.