Low Levels of Mannan-Binding Lectin or Ficolins Are Not Associated with an Increased Risk of Cytomegalovirus Disease in HIV-Infected Patients

Background

In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear.

Methods

In a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA.

Results

We analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log₁₀ ng/mL increase (95% CI 0.73–1.45)) nor with ficolins (OR per log₁₀ ng/mL increase 0.66 (95% CI 0.28–1.52), 2.34 (95% CI 0.44–12.36), and 0.89 (95% CI 0.26–3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log₁₀ copies/mL; 95% CI 1.08–2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84–0.98).

Conclusions

CMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.     

GlycA,a Pro-Inflammatory Glycoprotein Biomarker,and Incident Cardiovascular Disease: Relationship with C-Reactive Protein and Renal Function

Objective

GlycA is a novel nuclear magnetic resonance spectroscopy-measured biomarker of systemic inflammation. We determined whether GlycA is associated with incident cardiovascular disease (CVD) in men and women, examined whether this association with CVD is modified by renal function, and compared this association with high sensitivity C-reactive protein (hsCRP).

Research design and methods

A prospective cohort study was performed among 4,759 subjects (PREVEND study) without a history of CVD and cancer. Incident CVD was defined as the combined endpoint of cardiovascular morbidity and mortality. Cox regression analyses were used to examine associations of baseline GlycA and hsCRP with CVD.

Results

298 first CVD events occurred during a median follow-up of 8.5 years. After adjustment for clinical and lipid measures the hazard ratio (HR) for CVD risk in the highest GlycA quartile was 1.58 (95% CI, 1.05–2.37, P for trend = 0.004). This association was similar after further adjustment for renal function (estimated glomerular filtration rate and urinary albumin excretion). After additional adjustment for hsCRP, GlycA was still associated with incident CVD (HR: 1.16 per SD change (95% CI, 1.01–1.33), P = 0.04). Similar results were obtained for hsCRP (HR per SD change after adjustment for GlycA: 1.17 (95% CI 1.17 (95% CI, 1.01–3.60), P = 0.04). CVD risk was highest in subjects with simultaneously higher GlycA and hsCRP (fully adjusted HR: 1.79 (95% CI, 1.31–2.46), P<0.001).

Conclusion

GlycA is associated with CVD risk in men and women, independent of renal function. The association of GlycA with incident CVD is as strong as that of hsCRP.     

Does radiotherapy increase oxidative stress? A study with nasopharyngeal cancer patients revealing anomalies in isoprostanes measurements

Abstract

This study aimed to examine if exposure to ionizing radiation during clinical radiotherapy (RT) causes increased oxidative damage. Seven patients with nasopharyngeal cancer (NPC) who underwent RT took part in this controlled-trial study. Blood and urine samples were obtained for F₂-isoprostanes (F₂-IsoPs) measurement. Urinary F₂-IsoPs levels were elevated pre-treatment and remained high (but did not increase) during treatment, but decreased to the normal range after treatment. Plasma F₂-IsoPs decreased significantly after the start of treatment before rising midway through treatment. Levels decreased significantly to below baseline following treatment. However, the patients were observed to have substantially lower levels of plasma esterified arachidonic acid (AA) residues than controls. The data shows that NPC is associated with elevated F₂-isoprostanes in urine and in plasma after correction for decreased AA levels. RT did not increase these levels and, indeed, was associated with falls in F₂-IsoPs. The validity and usefulness of correction of plasma F₂-IsoPs for lowered AA levels is discussed.     

Obesity-Hypoventilation Syndrome: Increased Risk of Death over Sleep Apnea Syndrome

AimTo study whether mortality and cardiovascular morbidity differ in non-invasive ventilation (NIV)-treated patients with severe obesity-hypoventilation syndrome (OHS) as compared with CPAP-treated patients with obstructive sleep apnea syndrome (OSAS), and to identify independent predictors of mortality in OHS.ResultsThree hundred and thirty subjects (110 patients with OHS and 220 patients with OSAS) were studied. Mean follow-up time was 7±4 years. The five year mortality rates were 15.5% in OHS cohort and 4.5% in OSAS cohort (p< 0.05). Patients with OHS had a 2-fold increase (OR 2; 95% CI: 1.11–3.60) in the risk of mortality and 1.86 fold (OR 1.86; 95% CI: 1.14–3.04) increased risk of having a cardiovascular event. Diabetes, baseline diurnal SaO₂ < 83%, EPAP < 7 cmH2O after titration and adherence to NIV < 4 hours independently predicted mortality in OHS.ConclusionMortality of severe OHS is high and substantially worse than that of OSAS. Severe OHS should be considered a systemic disease that encompasses respiratory, metabolic and cardiovascular components that require a multimodal therapeutic approach.     

Epidemiology of Severe Acute Respiratory Illness (SARI) among Adults and Children Aged ≥5 Years in a High HIV-Prevalence Setting, 2009–2012

ObjectiveThere are few published studies describing severe acute respiratory illness (SARI) epidemiology amongst older children and adults from high HIV-prevalence settings. We aimed to describe SARI epidemiology amongst individuals aged ≥5 years in South Africa.MethodsWe conducted prospective surveillance for individuals with SARI from 2009–2012. Using polymerase chain reaction, respiratory samples were tested for ten viruses, and blood for pneumococcal DNA. Cumulative annual SARI incidence was estimated at one site with population denominators.FindingsWe enrolled 7193 individuals, 9% (621/7067) tested positive for influenza and 9% (600/6519) for pneumococcus. HIV-prevalence was 74% (4663/6334). Among HIV-infected individuals with available data, 41% of 2629 were receiving antiretroviral therapy (ART). The annual SARI hospitalisation incidence ranged from 325-617/100,000 population. HIV-infected individuals experienced a 13–19 times greater SARI incidence than HIV-uninfected individuals (p<0.001). On multivariable analysis, compared to HIV-uninfected individuals, HIV-infected individuals were more likely to be receiving tuberculosis treatment (odds ratio (OR):1.7; 95%CI:1.1–2.7), have pneumococcal infection (OR 2.4; 95%CI:1.7–3.3) be hospitalised for >7 days rather than <2 days (OR1.7; 95%CI:1.2–2.2) and had a higher case-fatality ratio (8% vs 5%;OR1.7; 95%CI:1.2–2.3), but were less likely to be infected with influenza (OR 0.6; 95%CI:0.5–0.8). On multivariable analysis, independent risk indicators associated with death included HIV infection (OR 1.8;95%CI:1.3–2.4), increasing age-group, receiving mechanical ventilation (OR 6.5; 95%CI:1.3–32.0) and supplemental-oxygen therapy (OR 2.6; 95%CI:2.1–3.2).ConclusionThe burden of hospitalized SARI amongst individuals aged ≥5 years is high in South Africa. HIV-infected individuals are the most important risk group for SARI hospitalization and mortality in this setting.     

Isoprostanes and isofurans as non-traditional risk factors for cardiovascular disease among Canadian Inuit

Abstract

Objectives: The aim of the present study was to investigate the potential importance of oxidative stress, measured by isoprostanes-related compounds, as non-traditional risk factor for cardiovascular disease. We planned to examine the relationship between concentrations of plasma F₂-isoprostanes (F₂-IsoPs), isofurans (IsoFs), measures of obesity and various cardiometabolic risk factors. Materials and methods: Cross-sectional study using a sub-sample from the population of a survey conducted in the summer and fall 2007 and 2008 by Canadian Coastguard Ship Amundsen in 36 Canadian Arctic Inuit communities. Subjects included a subset (n =?233) of a total study population (n =?2595) with a mean age 42.56 ± 15.39 years and body mass index 27.78 ± 5.65 kg/m². Plasma levels of F₂-IsoPs and IsoFs was determined by gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method; and their relationships to waist circumference (WC), blood pressure C reactive proteins (CRP), blood lipids and fasting glucose were assessed by multivariate analyses. Results: Plasma F₂-IsoPs correlated positively with CRP (r =.132, P =.048) and systolic blood pressure (SBP) (r =.157, P =.024) after adjustment for age, sex and body mass index. IsoFs correlated with WC (r =.190, P =.005) and SBP (r =.137, P =.048). F2-IsoPs were not found elevated in smokers (P =.034), whereas IsoFs were decreased in smokers (P =.001). WC, SBP and sex were found to be major correlates of oxidative stress in Canadian Inuit. Conclusions: Plasma measures of F₂-IsoPs and IsoFs increase with increased obesity and associated cardiometabolic risk factors, including CRP and blood pressure. Simultaneous measurement of IsoFs provides an advantageous mechanistic insight into oxidative stress not captured by F₂-IsoPs alone.     

Hemoglobin May Contribute to Sex Differences in Mortality among HIV-Infected Persons in Care

Background

Some retrospective studies have found that HIV-infected women have a higher mortality risk than men after adjusting for baseline characteristics, while others have not. Anemia is a known predictor of HIV-related mortality. We assessed whether anemia contributed to the sex difference in mortality in our cohort.

Methods

We conducted a retrospective cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between 1998 and 2009. Cox proportional hazards models compared time from first clinic visit to death and AIDS-defining events (ADE), adjusted for baseline characteristics with and without baseline hemoglobin.

Results

Of 3,633 persons, 879 (24%) were women. Women had lower median baseline hemoglobin compared to men: 12.4 g/dL (inter-quartile range (IQR) 11.3–13.4) vs. 14.4 (IQR 13.1–15.5), respectively (P<0.001). In multivariable models without hemoglobin, the risk of death was higher among women: hazard ratio (HR) 1.46 (95% confidence interval (CI) 1.17, 1.82; P = 0.001). In multivariable models with hemoglobin, the risk of death in women was diminished and no longer statistically significant: HR 1.2 (95% CI 0.93, 1.55; P = 0.17). The risk of ADE was higher among women in both models, but not statistically significant: HR 1.1 (95% CI 0.85–1.42; P = 0.46) in the model without hemoglobin and 1.11 (95% CI 0.82–1.48; P = 0.50) in the model with hemoglobin. Hemoglobin was a strong predictor of death: HR 0.88 per 1 g/dL increase (95% CI 0.83, 0.93; P<0.001).

Conclusion

In our study population of HIV-infected persons in care, women had lower baseline hemoglobin, and lower hemoglobin contributed to their higher risk of ADE and death.     

Body Mass Index,High-Sensitivity C-Reactive Protein and Mortality in Chinese with Coronary Artery Disease

Background

To investigate single and joint associations of body mass index (BMI) and serum high-sensitivity C-reactive protein (hsCRP) with death.

Methods

The study included 1871 coronary artery disease (CAD) patients aged 40–85 year-old recruited from 2008 to 2011. Cox regression models were used to estimate the association of BMI and hsCRP with mortality. The data was analyzed in 2014.

Results

During 3.1 years follow-up, 141 deaths were recorded, 110 died of cardiovascular disease (CVD). After adjustment of major CVD risk factors, there was a J-shaped association between BMI and all-cause and CVD mortality, and a positive association between hsCRP and mortality. The J-shaped association of BMI with mortality was present among patients who never smoked or with elevated hsCRP (≥3.0 mg/L). Compared with overweight (BMI 24–27.9 kg/m²) patients with normal hsCRP (<3.0 mg/L), obese patients (BMI≥28 kg/m²) with elevated hsCRP had a 3.41-fold risk of all-cause mortality (95% CI 1.49–7.80) and a 3.50-fold risk of CVD mortality (1.40–8.75), lean patients (BMI<24 kg/m²) with elevated hsCRP concentration had a 2.54-fold risk of all-cause mortality (1.36–4.74) and a 2.36-fold risk of CVD mortality (1.19–4.70).

Conclusions

The association pattern between baseline BMI and mortality changed among different baseline hsCRP concentrations, indicating that low-grade inflammation may be related to BMI and secondary prognosis of CAD.     

Prognostic Value of Lactate and Central Venous Oxygen Saturation after Early Resuscitation in Sepsis Patients

The objective of this study was to evaluate the prognostic value of static and dynamic variables of central venous oxygen saturation (ScvO₂) and lactate in patients with severe sepsis or septic shock who underwent early quantitative resuscitation. We also investigated whether ScvO₂ measured after initial resuscitation could provide additive prognostic value to that of lactate. We analyzed the sepsis registry for patients presenting to the emergency department and included patients with simultaneous measurements of lactate and ScvO₂ at the time of presentation (H0) and 6 hours (H6) after resuscitation. The primary outcome was 28-day mortality and multivariable logistic analysis was used to adjust for confounders. A total of 363 patients were included, and the overall 28-day mortality was 18%. The area under the receiver operator characteristic curve for predicting 28-day mortality was as follows: lactate (H6), 0.81; lactate (H0), 0.73; relative lactate change, 0.67; ScvO₂ (H6), 0.65; relative ScvO₂ change 0.59; ScvO₂ (H0), 0.58. Patients with lactate normalization showed significantly lower 28-day mortality compared to patients without lactate normalization (3% vs. 28%, P<0.01). However, in those who achieved ScvO₂ (H6) ≥70%, there was a significant difference in 28-mortality only in patients without lactate normalization (21% vs. 39%, P<0.01) but no difference in those with lactate normalization (4% vs. 3%, P = 0.71). In multivariable analysis, lactate normalization was significantly associated with 28-day mortality (adjusted odds ratio [OR] for 28-day mortality, 0.20; 95% confidence interval [CI], 0.07–0.54; P <0.01), but ScvO₂ (H6) ≥70% showed only a marginal association (the adjusted OR for 28-day mortality, 0.51; 95% CI, 0.26–1.01; P = 0.05). ScvO₂ (H6) ≥70% was associated with 28-day mortality only in cases without lactate normalization in subgroup analysis (adjusted OR 0.37, 95% CI, 0.18–0.79; P = 0.01). Six-hour lactate was the strongest predictor of 28-day mortality in patients with severe sepsis or septic shock. Six-hour ScvO₂ provided additional prognostic value only in cases where lactate values were not normalized after resuscitation.     

F2-Isoprostanes in HDL are bound to neutral lipids and phospholipids

Low HDL cholesterol (HDL-C) is a risk factor for coronary artery disease (CAD). However, interventions that raise HDL-C have failed to reduce cardiovascular events. We previously reported that HDL is the main carrier of plasma F₂-isoprostanes (F₂-IsoPs) that are markers of oxidative stress formed upon oxidation of arachidonic acid. F₂-IsoPs are predominantly associated with phospholipids. However, there is evidence that F₂-IsoPs in the liver of rats treated with carbon tetrachloride associate with the neutral lipids. To date it is not known whether F₂-IsoPs are found in the neutral lipids in HDL in humans. Possible candidate neutral lipids include cholesteryl esters, triglycerides, diglycerides, and monoglycerides. This study aimed to identify the lipid classes within native and oxidized HDL that contain F₂-IsoPs. We showed that F₂-IsoPs in HDL are bound to neutral lipids as well as phospholipids. HDL-3 contained the highest concentration of F₂-IsoPs in all lipid classes before and after in vitro oxidation. Using targeted LC/MS and high resolution MS, we were unable to provide conclusive evidence for the presence of the synthesized standards 15(R)-15-F_2t-isoP cholesterol and 1-ent-15(RS)-15-F_2t-isoprostanoyl-sn-glycerol in the neutral lipids of HDL. Our findings show that oxidized lipids such as F₂-IsoPs are found in the core and surface of HDL. However, the exact molecular species remain to be definitively characterized. Future studies are required to determine whether the presence of F₂-IsoPs in neutral lipids alters HDL function.     

Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008

BackgroundAn association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa.MethodsIPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003–2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent.ResultsAmong 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1–3.5) and 19F (OR 2.9, 95%CI 1.4–6.1) vs. serotype 4; increasing age (25–44 years, OR 1.8, 95%CI 1.0–3.0; 45–64 years, OR 3.6, 95%CI 2.0–6.4; ≥65 years, OR 5.2, 95%CI 1.9–14.1; vs. 15–24 years); meningitis (OR 4.1, 95%CI 3.0–5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0–2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases.ConclusionMortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.     

Association of hsCRP,White Blood Cell Count and Ferritin with Renal Outcome in Chronic Kidney Disease Patients

Inflammation is a pathogenic factor in renal injury, but whether inflammation is related to renal outcome in chronic kidney disease (CKD) patients is little known. We thus assess the association of inflammation and renal outcome in an advanced CKD cohort. This study analyzed the association between inflammatory markers, such as C-reactive protein (hsCRP), white blood cell (WBC) count and ferritin, renal replacement therapy (RRT) and rapid renal progression (estimated GFR slope<-6 ml/min/1.73 m²/y) in 3303 patients with stage 3–5 CKD. In all subjects, the mean hsCRP, WBC count, and ferritin levels were 1.2 (0.4, 5.4) mg/L, 7.2±2.3×10³ cells/µL, and 200 (107,349) ng/mL, respectively. During a mean 3.2-year follow-up, there were 1080 (32.7%) subjects commencing RRT, and 841(25.5%) subjects presenting rapid renal progression. Both hsCRP and ferritin were associated with increased risk for RRT with the adjusted HR (tertile 3 versus tertile 1∶1.17 〔1.01–1.36〕 and 1.20 〔1.03–1.40〕, respectively). Both hsCRP and ferritin were associated with increased odds for rapid renal progression with the adjusted OR (tertile 3 versus tertile 1∶1.40 〔1.13–1.77〕 and 1.32 〔1.06–1.67〕, respectively). hsCRP and ferritin stratified by albumin were also associated with RRT and rapid renal progression. Instead, WBC count was not associated with renal outcome. In conclusion, elevated levels of hsCRP and ferritin are risk factors associated with RRT and rapid renal progression in advanced CKD patients.     

Correlation of F4-neuroprostanes levels in cerebrospinal fluid with outcome of aneurysmal subarachnoid hemorrhage in humans

Aneurysmal subarachnoid hemorrhage (aSAH) is one type of hemorrhagic stroke in humans. F₂-isoprostanes (F₂-IsoPs) and F₄-neuroprostanes (F₄-NPs), derived from arachidonic acid and docosahexaenoic acid (DHA), respectively, are specific markers of lipid peroxidation. We previously demonstrated that F₂-IsoPs levels in cerebrospinal fluid (CSF) of aSAH patients positively correlated with poor clinical conditions. In this work, we refined F₄-NPs analysis and investigated the role of potential oxidative damage to neurons in aSAH patients by detecting F₄-NPs in CSF. [²H₄]-15-F_2t-IsoP, rather than [¹⁸O₂]-17-F_4c-NP or [²H₄]-PGF_2α, was used as the internal standard for F₄-NPs analysis. One problem of the use of [¹⁸O₂]-17-F_4c-NP was the potential interference resulting from F₂-dihomo-IsoPs in CSF. CSF specimens of 15 aSAH patients for up to 10 days and those of 12 non-aSAH controls were analyzed. First day, mean, and peak levels of F₄-NPs were all significantly higher in aSAH patients than in controls and correlated with the Fisher Scale and 3-month Glasgow Outcome Scale, but only mean levels of F₄-NPs correlated with Hunt and Hess Grade. The results first demonstrate oxidative damage to DHA in brain tissue following aSAH and suggest that F₄-NPs in CSF could be a better predictor for outcome of aSAH than F₂-IsoPs at early time points.     

Traditional Risk Factors Are More Relevant than HIV-Specific Ones for Carotid Intima-Media Thickness (cIMT) in a Brazilian Cohort of HIV-Infected Patients

BackgroundCombination antiretroviral therapy (cART) had a dramatic impact on the mortality profile in human immunodeficiency virus (HIV) infected individuals and increased their life-expectancy. Conditions associated with the aging process have been diagnosed more frequently among HIV-infected patients, particularly, cardiovascular diseases.MethodsPatients followed in the Instituto de Pesquisa Clínica Evandro Chagas (IPEC) prospective cohort in Rio de Janeiro were submitted to the general procedures from the Brazilian Longitudinal Study of Adult Health, comprising several anthropometric, laboratory and imaging data. Carotid intima-media thickness (cIMT) was measured by ultrasonography, following the Mannheim protocol. Linear regression and proportional odds models were used to compare groups and covariables in respect to cIMT. The best model was chosen with the adaptive lasso procedure.ResultsA valid cIMT exam was available for 591 patients. Median cIMT was significantly larger for men than women (0.56mm vs. 0.53mm; p = 0.002; overall = 0.54mm). In univariable linear regression analysis, both traditional risk factors for cardiovascular diseases (CVD) and HIV-specific characteristics were significantly associated with cIMT values, but the best multivariable model chosen included only traditional characteristics. Hypertension presented the strongest association with higher cIMT terciles (OR = 2.51; 95%CI = 1.69–3.73), followed by current smoking (OR = 1,82; 95%CI = 1.19–2.79), family history of acute myocardial infarction or stroke (OR = 1.60; 95%CI = 1.10–2.32) and age (OR per year = 1.12; 95%CI = 1.10–1.14).ConclusionsOur results show that traditional cardiovascular disease (CVD) risk factors are the major players in determining increased cIMT among HIV infected patients in Brazil. This finding reinforces the need for thorough assessment of those risk factors in these patients to guarantee the incidence of CVD events remain under control.     

Trends in the Use of Guideline-Recommended Medications and In-Hospital Mortality of Patients with Acute Myocardial Infarction in a Chinese Population

ObjectiveCurrent practice guidelines recommend the routine use of several cardiac medications early in the course of acute myocardial infarction (AMI). Our objective was to analyze temporal trends in medication use and in-hospital mortality of AMI patients in a Chinese population.MethodsThis is a retrospective observational study using electronic medical records from the hospital information system (HIS) of 14 Chinese hospitals. We identified 5599 patients with AMI between 2005 and 2011. Factors associated with medication use and in-hospital mortality were explored by using hierarchical logistic regression.ResultsThe use of several guideline-recommended medications all increased during the study period: statins (57.7%–90.1%), clopidogrel (61.8%–92.3%), β-Blockers (45.4%–65.1%), ACEI/ARB (46.7%–58.7%), aspirin (81.9%–92.9%), and the combinations thereof increased from 24.9% to 42.8% (P<0.001 for all). Multivariate analyses showed statistically significant increases in all these medications. The in-hospital mortality decreased from 15.9% to 5.7% from 2005 to 2011 (P<0.001). After multivariate adjustment, admission year was still a significant factor (OR = 0.87, 95% CI 0.79–0.96, P = 0.007), the use of aspirin (OR = 0.64, 95% CI 0.46–0.87), clopidogrel (OR = 0.44, 95% CI 0.31–0.61), ACEI/ARB (OR = 0.73, 95% CI 0.56–0.94) and statins (OR = 0.54, 95% CI 0.40–0.73) were associated with a decrease in in-hospital mortality. Patients with older age, cancer and renal insufficiency had higher in-hospital mortality, while they were generally less likely to receive all these medications.ConclusionUse of guideline-recommended medications early in the course of AMI increased between 2005 and 2011 in a Chinese population. During this same time, there was a decrease in in-hospital mortality.     

Oxidative stress in Rett syndrome: Natural history,genotype, and variants

Abstract

Objectives

Rett syndrome (RTT) is an X-linked autism spectrum disorder caused by mutations in the MeCP2 gene in the great majority of cases. Evidence suggests a potential role of oxidative stress (OS) in its pathogenesis. Here, we investigated the potential value of OS markers (non-protein-bound iron (NPBI) and F₂-isoprostanes (F₂-IsoPs)) in explaining natural history, genotype-phenotype correlation, and clinical heterogeneity of RTT, and gauging the response to omega-3 polyunsaturated fatty acids (ω-3 PUFAs).

Methods

RTT patients (n = 113) and healthy controls were assayed for plasma NPBI and F₂-IsoPs, and intraerythrocyte NPBI. Forty-two patients with typical RTT were randomly assigned to ω-3 PUFAs supplementation for 12 months. NPBI was measured by HPLC and F₂-IsoPs using a gas chromatography/negative ion chemical ionization tandem mass spectrometry (GC/NICI-MS/MS) technique.

Results

F₂-IsoPs were significantly higher in the early stages as compared with the late natural progression of classic RTT. MeCP2 mutations related to more severe phenotypes exhibited higher OS marker levels than those of milder phenotypes. Higher OS markers were observed in typical RTT and early seizure variant as compared with the preserved speech and congenital variants. Significant reduction in OS markers levels and improvement of severity scores were observed after ω-3 PUFAs supplementation.

Discussion

OS is a key modulator of disease expression in RTT.     

A Clinical Predictor Score for 30-Day Mortality among HIV-Infected Adults Hospitalized with Pneumonia in Uganda

BackgroundPneumonia is a major cause of mortality among HIV-infected patients. Pneumonia severity scores are promising tools to assist clinicians in predicting patients’ 30-day mortality, but existing scores were developed in populations infected with neither HIV nor tuberculosis (TB) and include laboratory data that may not be available in resource-limited settings. The objective of this study was to develop a score to predict mortality in HIV-infected adults with pneumonia in TB-endemic, resource-limited settings.MethodsWe conducted a secondary analysis of data from a prospective study enrolling HIV-infected adults with cough ≥2 weeks and <6 months and clinically suspected pneumonia admitted to Mulago Hospital in Kampala, Uganda from September 2008 to March 2011. Patients provided two sputum specimens for mycobacteria, and those with Ziehl-Neelsen sputum smears that were negative for mycobacteria underwent bronchoscopy with inspection for Kaposi sarcoma and testing for mycobacteria and fungi, including Pneumocystis jirovecii. A multivariable best subsets regression model was developed, and one point was assigned to each variable in the model to develop a clinical predictor score for 30-day mortality.ResultsOverall, 835 patients were studied (mean age 34 years, 53.4% female, 30-day mortality 18.2%). A four-point clinical predictor score was identified and included heart rate >120 beats/minute, respiratory rate >30 breaths/minute, oxygen saturation <90%, and CD4 cell count <50 cells/mm³. Patients’ 30-day mortality, stratified by score, was: score 0 or 1, 12.6%, score 2 or 3, 23.4%, score 4, 53.9%. For each 1 point change in clinical predictor score, the odds of 30-day mortality increased by 65% (OR 1.65, 95% CI 1.39-1.96, p <0.001).ConclusionsA simple, four-point scoring system can stratify patients by levels of risk for mortality. Rapid identification of higher risk patients combined with provision of timely and appropriate treatment may improve clinical outcomes. This predictor score should be validated in other resource-limited settings.     

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.     

Increased Risk of Serious Non-AIDS-Related Events in HIV-Infected Subjects on Antiretroviral Therapy Associated with a Low CD4/CD8 Ratio

Background

A low CD4/CD8 ratio has been identified in the general population as a hallmark of inmmunosenescence and a surrogate of all-cause mortality. We aimed to investigate in treated HIV-infected individuals the relationship between the CD4/CD8 ratio and serious non-AIDS events.

Methods

Case-control study within a prospective hospital-based cohort of HIV-infected subjects during at least one year of ART-mediated viral suppression. Cases were patients with serious non-AIDS events (non-AIDS malignancies, cardiovascular disease, and end-stage kidney disease), and controls individuals who did not developed non-AIDS events during follow-up. Data were analyzed using ROC analysis and multivariate logistic regression. Conditional logistic regression was performed in 200 cases/controls matched by age, sex, nadir CD4 and proximal CD4 counts.

Results

We analyzed 407 subjects (109 cases, 298 controls). The CD4/CD8 ratio was lower in cases (0.44 vs. 0.70, P<0.0001), with higher discriminatory ability for the detection of non-AIDS events than the CD4 count, CD8 count and nadir CD4. Multivariate analyses (adjusted for age, sex, nadir CD4, proximal CD4 count, year of ART initiation and ART duration) confirmed the independent association of a low CD4/CD8 ratio with the risk of non-AIDS morbidity (per CD4/CD8 ratio quartile decrease, OR, 2.9; 95% CI, 1.3–6.2) and non-AIDS mortality (OR, 2.8; 95% CI, 1.5–5.3).

Conclusions

The CD4/CD8 ratio provides additional information to the CD4 counts and nadir CD4 in treated HIV-infected individuals, since it is independently associated with the risk of non-AIDS-related morbidity and mortality. This association is robust and maintained within different subgroups of patients.