Effects of Clopidogrel on Mortality,Cardiovascular and Bleeding Outcomes in Patients with Chronic Kidney Disease - Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry

Background

The efficacy of clopidogrel is inconclusive in the chronic kidney disease (CKD) population with acute coronary syndrome (ACS). Furthermore, CKD patients are prone to bleeding with antiplatelet therapy. We investigated the efficacy and safety of clopidogrel in patients with ACS and CKD.

Methods

In a Taiwan national-wide registry, 2819 ACS patients were enrolled. CKD is defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m². The primary endpoints are the combined outcomes of death, non-fatal myocardial infarction and stroke at 12 months.

Results

Overall 949 (33.7%) patients had CKD and 2660 (94.36%) patients received clopidogrel treatment. CKD is associated with increased risk of the primary endpoint at 12 months (HR 2.39, 95% CI 1.82 to 3.15, p<0.01). Clopidogrel use is associated with reduced risk of the primary endpoint at 12 months (HR 0.42, 95% CI: 0.29–0.60, p<0.01). Cox regression analysis showed that clopidogrel reduced death and primary endpoints for CKD population (HR 0.35, 95% CI: 0.21–0.61 and HR 0.48, 95% CI: 0.30–0.77, respectively, both p<0.01). Patients with clopidogrel(−)/CKD(−), clopidogrel(+)/CKD(+) and clopidogrel(−)/CKD(+) have 2.4, 3.0 and 10.4 fold risk to have primary endpoints compared with those receiving clopidogrel treatment without CKD (all p<0.01). Clopidogrel treatment was not associated with increased in-hospital Thrombolysis In Myocardial Infarction (TIMI) bleeding in CKD population.

Conclusion

Clopidogrel could decrease mortality and improve cardiovascular outcomes without increasing risk of bleeding in ACS patients with CKD.     

Five-Year Incidence of Chronic Kidney Disease (Stage 3-5) and Associated Risk Factors in a Spanish Cohort: The MADIABETES Study

Objective

To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m²) among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use.

Design

The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).

Results

The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12–11.44) and the incidence density was 2.07 (95% CI = 1.83–2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19–2.79) cases per 100 patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was albuminuria ≥300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13–4.81), a history of Hypertension (HR = 2.02; 95% CI = 1.42–2.89), Myocardial Infarction (HR= 1.72; 95% IC= 1.25–2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30–2.17), duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88) and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02–2.24).

Conclusions

After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM.     

Adverse Outcomes of Anticoagulant Use among Hospitalized Patients with Chronic Kidney Disease: A Comparison of the Rates of Major Bleeding Events between Unfractionated Heparin and Enoxaparin

Background

Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding.

Objectives

To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH) and enoxaparin users.

Methods

One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10–59 ml/min/1.73 m²) who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes.

Results

Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05–10.35]). Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113]×10³/µL vs 205.56 [123] ×10³/µL; P<0.001), and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85–12.36]). Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03–6.25]); longer length of hospitalization (HR, 1.04 [95% CI, 1.01–1.06]); and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10–2.91]).

Conclusions

Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted.     

Impact of Renal Dysfunction on Mid-Term Outcome after Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis

Background

There is conflicting evidence regarding the impact of preexisting renal dysfunction (RD) on mid-term outcomes after transcatheter aortic valve implantation (TAVI) in patients with symptomatic aortic stenosis (AS).

Methods and results

Forty-seven articles representing 32,131 patients with AS undergoing a TAVI procedure were included in this systematic review and meta-analysis. Pooled analyses were performed with both univariate and multivariate models, using a fixed or random effects method when appropriate. Compared with patients with normal renal function, mid-term mortality was significantly higher in patients with preexisting RD, as defined by the author (univariate hazard ratio [HR]: 1.69; 95% confidence interval [CI]: 1.50–1.90; multivariate HR: 1.47; 95% CI: 1.17–1.84), baseline estimated glomerular filtration rate (eGFR) (univariate HR: 1.65; 95% CI: 1.47–1.86; multivariate HR: 1.46; 95% CI: 1.24–1.71), and serum creatinine (univariate HR: 1.69; 95% CI: 1.48–1.92; multivariate HR: 1.65; 95% CI: 1.36–1.99). Advanced stage of chronic kidney disease (CKD stage 3–5) was strongly related to bleeding (univariate HR in CKD stage 3: 1.30, 95% CI: 1.13–1.49; in CKD stage 4: 1.30, 95% CI: 1.04–1.62), acute kidney injure (AKI) (univariate HR in CKD stage 3: 1.28, 95% CI: 1.03–1.59; in CKD stage 4: 2.27, 95% CI: 1.74–2.96), stroke (univariate HR in CKD stage 4: 3.37, 95% CI: 1.52–7.46), and mid-term mortality (univariate HR in CKD stage 3: 1.57, 95% CI: 1.26–1.95; in CKD stage 4: 2.77, 95% CI: 2.06–3.72; in CKD stage 5: 2.64, 95% CI: 1.91–3.65) compared with CKD stage 1+2. Patients with CKD stage 4 had a higher incidence of AKI (univariate HR: 1.70, 95% CI: 1.34–2.16) and all-cause death (univariate HR: 1.60, 95% CI: 1.28–1.99) compared with those with CKD stage 3. A per unit decrease in serum creatinine was also associated with a higher mortality at mid-term follow-up (univariate HR: 1.24, 95% CI: 1.18–1.30; multivariate HR: 1.19, 95% CI: 1.08–1.30).

Conclusions

Preexisting RD was associated with increased mid-term mortality after TAVI. Patients with CKD stage 4 had significantly higher incidences of peri-procedural complications and a poorer prognosis, a finding that should be factored into the clinical decision-making process regarding these patients.     

Prognostic Significance of EBV Latent Membrane Protein 1 Expression in Lymphomas: Evidence from 15 Studies

Background

Epstein-Barr virus (EBV) infection has been associated with lymphoma development. EBV latent membrane protein 1 (LMP1) is essential for EBV-mediated transformation and progression of different human cells, including lymphocytes. This meta-analysis investigated LMP1 expression with prognosis of patients with lymphoma.

Methods

The electronic databases of PubMed, Embase, and Chinese Biomedicine Databases were searched. There were 15 published studies available for a random effects model analysis. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. A funnel plot was used to investigate publication bias, and sources of heterogeneity were identified by meta-regression analysis. The combined hazard ratios (HR) and their corresponding 95% confidence intervals of LMP1 expression were calculated by comparison to the overall survival.

Results

Overall, there was no statistical significance found between LMP1 expression and survival of lymphoma patients (HR 1.25 [95% CI, 0.92–1.68]). In subgroup analyses, LMP1 expression was associated with survival in patients with non-Hodgkin lymphoma (NHL) (HR  = 1.84, 95% CI: 1.02–3.34), but not with survival of patients with Hodgkin disease (HD) (HR  =  1.03, 95% CI: 0.74–1.44). In addition, significant heterogeneity was present and the meta-regression revealed that the outcome of analysis was mainly influenced by the cutoff value.

Conclusions

This meta-analysis demonstrated that LMP1 expression appears to be an unfavorable prognostic factor for overall survival of NHL patients. The data suggested that EBV infection and LMP1 expression may be an important factor for NHL development or progression.     

Traditional but Not HIV-Related Factors Are Associated with Nonalcoholic Fatty Liver Disease in Asian Patients with HIV-1 Infection

Background

The prevalence and factors associated with nonalcoholic fatty liver disease (NAFLD) are largely unknown in HIV-1 monoinfected patients.

Methods

The present study elucidated the prevalence and factors associated with NAFLD among Asian patients with HIV-1 infection who underwent abdominal ultrasonography between January 2004 and March 2013. Diagnosis of NAFLD was based on the liver to kidney contrast and diffusion in hepatic echogenicity. Uni- and multi-variate logistic regression analyses were applied to estimate factors associated with NAFLD.

Results

435 Asian patients free of chronic hepatitis B or C virus infection and without excessive alcohol intake were analyzed. NAFLD was diagnosed in 135 (31%) patients. Obesity (BMI >30 kg/m²) was evident in 18 (4.1%) patients, and BMI was >25 kg/m² in 103 (24%). Multivariate analysis identified higher BMI (per 1 kg/m² increment, adjusted OR = 1.198; 95% CI, 1.112–1.290; p<0.001), dyslipidemia (adjusted OR = 2.045; 95% CI, 1.183–3.538; p = 0.010), and higher ALT to AST ratio (per 1 increment, adjusted OR = 3.557; 95% CI, 2.129–5.941; p<0.001) as significant factors associated with NAFLD. No HIV-specific variables, including treatment with dideoxynucleoside analogues (didanosine, stavudine, and zalcitabine) and cumulative duration of antiretroviral therapy (ART), were associated with NAFLD.

Conclusions

The incidence of NALFD among Asian patients with HIV-1 infection is similar to that in Western countries. NAFLD was associated with high BMI, dyslipidemia, and high ALT/AST ratio, but not with HIV-related factors. The results highlight the importance of early recognition and management of NAFLD and traditional factors associated with NAFLD for Asian patients with HIV-1 infection.     

Prevalence and Risk Factors of CKD in Chinese Patients with Periodontal Disease

Background

Periodontal disease is common among adults and is associated with an increasing risk of chronic kidney disease (CKD). We aimed to investigate the prevalence and risk factors of CKD in patients with periodontal disease in China.

Methods

In the current cross-sectional study, patients with periodontal disease were included from Guangdong Provincial Stomatological Hospital between March 2011 and August 2011. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², the presence of albuminuria, or hematuria. All patients with periodontal disease underwent a periodontal examination, including periodontal probing pocket depth, gingival recession, and clinical attachment level by Florida Probe. They completed a questionnaire and had blood and urine samples taken. The adjusted prevalence of indicators of kidney damage was calculated and risk factors associated with CKD were analyzed.

Results

A total of 1392 patients with periodontal disease were invited to participate this study and 1268 completed the survey and examination. After adjusting for age and sex, the prevalence of reduced eGFR, albuminuria, and hematuria was 2.7% (95% CI 1.7–3.7), 6.7% (95% CI 5.5–8.1) and 10.9% (95% CI 9.2–12.5), respectively. The adjusted prevalence of CKD was 18.2% (95% CI 16.2–20.3). Age, male, diabetes, hypertension, history of CKD, hyperuricemia, and interleukin-6 levels (≥7.54 ng/L) were independent risk factors for reduced eGFR. Female, diabetes, hypertension, history of CKD, hyperuricemia, high level of cholesterol, and high sensitivity C-reactive protein (hsCRP) (≥1.03 mg/L) and TNF-α levels (≥1.12 ng/L) were independently associated with an increased risk of albuminuria. Female, lower education (<high school), and history of CKD were independent risk factors for hematuria.

Conclusions

18.2% of Chinese patients with periodontal disease have proteinuria, hematuria, or reduced eGFR, indicating the presence of kidney damage. Whether prevention or treatment of periodontal disease can reduce the high prevalence of CKD, however, remains to be further investigated.     

Relation between Mild to Moderate Chronic Kidney Disease and Coronary Artery Disease Determined with Coronary CT Angiography

Background

Both end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors.

Methods

A total of 2,038 patients with symptoms of chest discomfort suspected for coronary artery disease underwent coronary CT-angiography. We assessed traditional risk factors, coronary calcium score and coronary plaque characteristics (morphology and degree of luminal stenosis). Patients were subdivided in three groups, based on their estimated glomerular filtration rate (eGFR) Normal renal function (eGFR ≥90 mL/min/1.73 m²); mild CKD (eGFR 60–89 mL/min/1.73 m²); and moderate CKD (eGFR 30–59 mL/min/1.73 m²).

Results

Coronary calcium score increased significantly with decreasing renal function (P<0.001). Coronary plaque prevalence was higher in patients with mild CKD (OR 1.83, 95%CI 1.52–2.21) and moderate CKD (OR 2.46, 95%CI 1.69–3.59), compared to patients with normal renal function (both P<0.001). Coronary plaques with >70% luminal stenosis were found significantly more often in patients with mild CKD (OR 1.67 (95%CI 1.16–2.40) and moderate CKD (OR2.36, 95%CI 1.35–4.13), compared to patients with normal renal function (both P<0.01). After adjustment for traditional cardiovascular risk factors, the association between renal function and the presence of any coronary plaque as well as the association between renal function and the presence of coronary plaques with >70% luminal stenosis becomes weaker and were no longer statistically significant.

Conclusion

Although decreasing renal function is associated with increasing extent and severity of coronary artery disease, mild to moderately CKD is not independently associated with coronary plaque burden after adjustment for traditional cardiovascular risk factors.     

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes High Risk for Chronic Kidney Disease in Asian Male with Hypertension–A Meta-Regression Analysis of 98 Observational Studies

Background

Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial.

Objectives

This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk.

Data sources

PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013.

Study eligibility criteria, participants, and interventions

Cross-sectional surveys and case–control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity.

Study appraisal and synthesis methods

The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models.

Results

Ethnicity [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.08–1.42] and hypertension (OR: 1.55; 95% CI: 1.04–2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p<0.05). In subgroup analyses, this result was significant in the nondiabetic nephropathy group. Compared with the I allele, the D allele had the highest risk (OR: 3.75; 95% CI: 1.84–7.65) for CKD in hypertensive Asian males.

Conclusions and implications of key findings

The ACE I/D polymorphisms may incur the highest risk for increasing CKD in hypertensive Asian males.     

Associations between Longer Habitual Day Napping and Non-Alcoholic Fatty Liver Disease in an Elderly Chinese Population

Context

Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease (NAFLD) are associated with diabetes and inflammation, but the association between day napping and NAFLD remains unexplored.

Objective

To investigate the association between the duration of habitual day napping and NAFLD in an elderly Chinese population and to gain insight into the role of inflammatory cytokines in this association.

Design and Setting

We conducted a series of cross-sectional studies of the community population in Chongqing, China, from 2011 to 2012.

Participants

Among 6998 participants aged 40 to 75 years, 6438 eligible participants were included in the first study and analyzed to observe the association between day napping duration and NAFLD. In a separate study, 80 non-nappers and 90 nappers were selected to identify the role of inflammatory cytokines in this association. Logistic regression models were used to examine the odds ratios (ORs) of day nap duration with NAFLD.

Results

Day nappers had a significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration was associated in a dose-dependent manner with NAFLD (P trend <0.001). After adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13–2.46) for those reporting 0.5–1 h and 1.49 (95% CI 1.01–2.19) for those reporting >1 h of day napping compared with individuals who did not take day naps (all P<0.05). Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001). After adjusting for IL-6, PGRN, and SFRP5, the association between day napping duration and NAFLD disappeared (all P>0.05).

Conclusion

Longer day napping duration is associated with a higher prevalence of NAFLD, and inflammatory cytokines may be an essential link between day napping and NAFLD.     

Association between the PNPLA3 I148M Polymorphism and Non-Alcoholic Fatty Liver Disease in the Uygur and Han Ethnic Groups of Northwestern China

Objective

Multiple common gene variants play a role in non-alcoholic fatty liver disease (NAFLD) susceptibility. Our goal was to investigate the association between variants polymorphisms and NAFLD in the Uygur and Han from Northwestern China.

Methods

Eight tag single nucleotide polymorphisms (tSNPs) previously reported to be associated with NAFLD were characterized in 396 NAFLD individuals and 399 controls. The association of variants with NAFLD in the Uygur and Han was assessed using the chi-squared (χ²) test in different gene models. Unconditional logistic regression analysis was performed to obtain the odds ratios (ORs) for risk of NAFLD and their 95% confidence intervals (CI), adjusted for confounding factors. Finally, stratified analysis was used to explore the potential gene-environment interactions on the risk of NAFLD.

Results

In a recessive model, we found a potential association between rs738409 and NAFLD in both ethnic groups: Chinese Han (OR = 1.84, 95% CI: 1.03–3.27, p = 0.036), Uygur (OR = 2.25, 95% CI: 1.23–4.09, p = 0.006). The multiple logistic regression revealed that PNPLA3 rs738409 GG genotype may increase the risk of NAFLD by adjusting some confounding factors: Han (OR = 5.22, 95% CI: 1.94–14.04, p = 0.001), Uygur (OR = 4.29, 95% CI: 1.60–11.48, p = 0.004). Stratified analysis found that rs738409 polymorphism appeared to have interaction with sex, smoking status in Uygur, and have interaction with sex, age, BMI stage, lifestyle in Han.

Conclusion

Our data suggest the PNPLA3 I148M polymorphism influences susceptibility to NAFLD in the Han and Uygur of Northwestern China.     

Efficacy and Safety of Vitamin K-Antagonists (VKA) for Atrial Fibrillation in Non-Dialysis Dependent Chronic Kidney Disease

Background

Essential information regarding efficacy and safety of vitamin K-antagonists (VKA) treatment for atrial fibrillation (AF) in non-dialysis dependent chronic kidney disease (CKD) is still lacking in current literature. The aim of our study was to compare the risks of stroke or transient ischemic attack (TIA) and major bleeds between patients without CKD (eGFR >60 ml/min), and those with moderate (eGFR 30–60 ml/min), or severe non-dialysis dependent CKD (eGFR <30 ml/min).

Methods

We included 300 patients without CKD, 294 with moderate, and 130 with severe non-dialysis dependent CKD, who were matched for age and sex. Uni- and multivariate Cox regression analyses were performed reporting hazard ratios (HRs) for the endpoint of stroke or TIA and the endpoint of major bleeds as crude values and adjusted for comorbidity and platelet-inhibitor use.

Results

Overall, 6.2% (45/724, 1.7/100 patient years) of patients developed stroke or TIA and 15.6% (113/724, 4.8/100 patient years) a major bleeding event. Patients with severe CKD were at high risk of stroke or TIA and major bleeds during VKA treatment compared with those without renal impairment, HR 2.75 (95%CI 1.25–6.05) and 1.66 (95%CI 0.97–2.86), or with moderate CKD, HR 3.93(1.71–9.00) and 1.86 (95%CI 1.08–3.21), respectively. These risks were similar for patients without and with moderate CKD. Importantly, both less time spent within therapeutic range and high INR-variability were associated with increased risks of stroke or TIA and major bleeds in severe CKD patients.

Conclusions

VKA treatment for AF in patients with severe CKD has a poor safety and efficacy profile, likely related to suboptimal anticoagulation control. Our study findings stress the need for better tailored individualised anticoagulant treatment approaches for patients with AF and severe CKD.     

Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study

Background

Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.

Methods

We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.

Results

The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.

Conclusions

ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.     

Prognostic Value and Clinicopathological Differences of HIFs in Colorectal Cancer: Evidence from Meta-Analysis

Background

The prognostic value of HIFs in colorectal cancer was evaluated in a large number of studies, but the conclusions were inconclusive. Meanwhile, clinicopathologic differences of HIF-1α and HIF-2α were rarely compared in recent studies.

Methodology

Identical search strategies were used to search relevant literatures in the PubMed and Web of Science databases. The prognostic significances and clinicopathological differences of HIFs in CRC were analyzed.

Principal Findings

A total of 23studies comprising 2984 CRC patients met the inclusion criteria. The results indicated that overexpressed HIFs were significantly associated with increase of mortality risk, including overall survival (OS) (HR 2.06 95%CI 1.55–2.74) and disease free survival (HR 2.84, 95%CI 1.87–4.31). Subgroup analysis revealed that both overexpressed HIF-1α and HIF-2α had correlations with worse prognosis. The pooled HRs were 2.01 (95% CI: 1.55–2.6) and 2.07(95% CI: 1.01–4.26). Further subgroup analysis on HIF-1α was performed by study location, number of patients, quality score and cut-off value. The results showed that HIF-1α overexpression was significantly associated with poor OS, particularly in Asian countries (HR 2.3, 95% CI: 1.74–3.01), while not in European or other countries. In addition, overexpression of HIF-1α was closely related with these clinicopathological features, including Dukes'' stages (OR 0.39, 95% CI: 0.17–0.89), UICC stages (OR 0.42 95% CI: 0.3–0.59), depth of invasion (OR 0.71, 95% CI: 0.51–0.99), lymphnode status (OR 0.49, 95% CI: 0.32–0.73) and metastasis (OR 0.29, 95% CI: 0.11–0.81). While overexpression of HIF-2α was only associated with grade of differentiation (OR 0.48, 95% CI: 0.29–0.81).

Conclusions

This study showed that both HIF-1α and HIF-2α overexpression were associated with an unfavorable prognosis. HIF-1α overexpression seemed to be associated with worse prognosis in Asian countries. Additionally, HIF-1α and HIF-2α indicated distinct clinicopathologic features.     

Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis

Background

The prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer.

Materials and Methods

A literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted.

Results

This meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22–2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18–1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34–3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45–2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62–1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87–8.85).

Conclusion

Our study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer.     

All-Cause and Cause-Specific Mortality after Long-Term Sickness Absence for Psychiatric Disorders: A Prospective Cohort Study

Objective

The aim was to examine if long-term psychiatric sickness absence was associated with all-cause and diagnosis-specific (cardiovascular disease (CVD), cancer and suicide) mortality for the period 1990–2007. An additional aim was to examine these associations for psychiatric sickness absence in 1990 and 2000, with follow-up on mortality during 1991–1997 and 2001–2007, separately.

Methods

Employees within municipalities and county councils, 244,990 individuals in 1990 and 764,137 individuals in 2000, were followed up to 2007 through register linkages. Analyses were conducted with flexible parametric survival models comparing sickness absentees due to psychiatric diagnoses (>90 days) with those not receiving sick leave benefit.

Results

Long-term sickness absence for psychiatric disorders was associated with an increased risk of mortality due to all causes; CVD; cancer (smoking and non-smoking related); and suicide during the period 1990–2007. After full adjustment for socio-demographic covariates and previous inpatient care due to somatic and psychiatric diagnoses, these associations remained significant for all-cause mortality (Hazard ratios (HR) and 95% confidence interval (CI)): HR 1.56, 95% CI 1.3–1.8; CVD: HR 1.35, 95% CI 1.0–1.9, and suicide: HR 3.84, 95% CI 2.4–6.1. For both cohorts 1990 and 2000 estimates point in the same direction. For the time-period 2000–2007, we found increased risks of mortality in the fully adjusted model due to all causes: HR 1.47, 95% CI 1.2–1.7; CVD: HR 1.83, 95% CI 1.2–2.7; overall cancer: HR 1.33, 95% CI 1.0–1.7; and suicide: HR 2.15, 95% CI 1.3–3.7.

Conclusion

Long-term sickness absence for psychiatric disorders predicted premature mortality from all-causes, cardiovascular disease, cancer, and suicide.     

Serum Vitamin D in Patients with Chronic Obstructive Lung Disease Does Not Correlate with Mortality – Results from a 10-Year Prospective Cohort Study

Background

Recent studies have found vitamin D (25-OHD) deficiency and insufficiency to be common among patients with COPD. Serum level of 25-OHD seems to correlate to pulmonary function, COPD disease staging, and increased susceptibility to respiratory infections. We wanted to investigate whether vitamin D deficiency or insufficiency was associated with mortality rate in patients suffering from advanced COPD.

Methods

25-OHD serum levels were measured in 462 patients suffering from moderate to very severe COPD. Patients were stratified into three groups according to serum levels of 25-OHD. Outcome measure was mortality in a 10 year follow-up period. Kaplan-Meier curves (KM) were plotted and mortality hazard ratios (HR) were calculated using Cox Proportional Hazard regression (Cox PH).

Results

Serum 25-OHD deficiency and insufficiency were prevalent. We were unable to demonstrate any association between baseline serum levels of 25-OHD and mortality rate. We found an association between mortality and age [HR 1.05 (CI 95%: 1.03–1.06)], Charlson score [HR 1.49 (CI 95%: 1.06–2.09)], increasing neutrophil count [HR 1.05 (CI 95%: 1.02–1.09)], severe [HR 1.41 (CI 95%: 1.06–1.86)]/very severe COPD [HR 2.19 (CI 95%: 1.58–3.02)] and a smoking history of more than 40 pack years [HR 1.27 (CI 95%: 1.02–1.70)].

Conclusions

Serum level of 25-OHD does not seem to be associated with mortality rate, suggesting no or only a minor role of 25-OHD in disease progression in patients with moderate to very severe COPD.     

High Weight Loss during Radiation Treatment Changes the Prognosis in Under-/Normal Weight Nasopharyngeal Carcinoma Patients for the Worse: A Retrospective Analysis of 2433 Cases

Background

Although weight loss is common in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy, the prognostic influence of weight loss and its impact modified by body mass index (BMI) are still unclear.

Methods

2433 NPC patients receiving radical radiotherapy at Sun Yat-sen University Cancer Center from November, 2000 to December, 2004 were enrolled. Weight change during radiation treatment was categorized into high weight loss (HWL) and low weight loss (LWL). The associations of HWL with overall survival (OS) and disease-specific survival (DSS) were analyzed by Cox regression.

Results

Among underweight patients, HWL was independently associated with poor OS (hazard ratio [HR], 2.06; 95% CI 1.36–3.11) and DSS (HR, 2.27; 95% CI 1.38–3.73), as compared with LWL, after adjusting for covariates. In normal weight patients, the impact of HWL on OS (HR, 1.47; 95% CI 1.19–1.80) and DSS (HR, 1.59; 95% CI 1.24–2.03) was moderate. Among overweight/obese patients, no significant association between HWL and OS (HR, 1.22; 95% CI 0.95–1.55), or DSS (HR, 1.23; 95% CI 0.93–1.64) was found.

Conclusion

Except for overweight/obese patients, high weight loss during radiation treatment was independently associated with poor survival in NPC. This impact was more prominent in the underweight patient group.     

Association of Angiopoietin-2 with Renal Outcome in Chronic Kidney Disease

Background

The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians'' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.

Methods

This study enrolled 621 patients with stages 3–5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m²/y) over follow-up of more than 3 years.

Results

Of all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06–2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13–7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.

Conclusions

Ang-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.     

Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

Background

Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population.

Methods

We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes.

Results

During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14–1.70), coronary heart disease (HR 1.72, 95%CI 1.11–2.66), heart failure (HR 2.87, 95%CI 2.17–3.80), stroke (HR 1.56, 95%CI 0.99–2.46), AF (HR 5.75, 95%CI 4.43–7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9–67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51–2.66), AF (HR 4.25, 95%CI 3.28–5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8–32.1).

Conclusion

Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.