Intake of Gnetum Africanum and Dacryodes Edulis, Imbalance of Oxidant/Antioxidant Status and Prevalence of Diabetic Retinopathy in Central Africans

Objective

To estimate the prevalence of DR and to correlate cardiometabolic, sociodemographic, and oxidant/antioxidant imbalance data to the prevalence of DR.

Design

This case-control study included type 2 DM (T2 DM) patients with DR (n = 66), T2 DM patients without DR (N = 84), and healthy controls (n = 45) without DR, in Kinshasa town. Diet, albuminemia, serum vitamins, and 8-isoprostane were examined.

Results

No intake of safou (OR = 2.7 95% CI 1.2–5.8; P = 0.014), low serum albumin <4.5 g/dL (OR-2.9 95% CI 1.4–5.9; P = 0.003), no intake of fumbwa (OR = 2.8 95% CI 1.2–6.5; P = 0.014), high 8-isoprostane (OR = 14.3 95% CI 4.5–46; P<0.0001), DM duration ≥5 years (OR = 3.8 95% CI 1.6–9.1; P = 0.003), and low serum vitamin C (OR = 4.5 95% CI 1.3–15.5; P = 0.016) were identified as the significant independent determinants of DR.

Conclusion

The important role of oxidant/antioxidant status imbalance and diet is demonstrated in DR.     

Prolactin secretion in healthy adults is determined by gender, age and body mass index

Background

Prolactin (PRL) secretion is quantifiable as mean, peak and nadir PRL concentrations, degree of irregularity (ApEn, approximate entropy) and spikiness (brief staccato-like fluctuations).

Hypothesis

Distinct PRL dynamics reflect relatively distinct (combinations of) subject variables, such as gender, age, and BMI.

Location

Clinical Research Unit.

Subjects

Seventy-four healthy adults aged 22–77 yr (41 women and 33 men), with BMI 18.3–39.4 kg/m².

Measures

Immunofluorometric PRL assay of 10-min samples collected for 24 hours.

Results

Mean 24-h PRL concentration correlated jointly with gender (P<0.0001) and BMI (P = 0.01), but not with age (overall R² = 0.308, P<0.0001). Nadir PRL concentration correlated with gender only (P = 0.017) and peak PRL with gender (P<0.001) and negatively with age (P<0.003), overall R² = 0.325, P<0.0001. Forward-selection multivariate regression of PRL deconvolution results demonstrated that basal (nonpulsatile) PRL secretion tended to be associated with BMI (R² = 0.058, P = 0.03), pulsatile secretion with gender (R² = 0.152, P = 0.003), and total secretion with gender and BMI (R² = 0.204, P<0.0001). Pulse mass was associated with gender (P = 0.001) and with a negative tendency to age (P = 0.038). In male subjects older than 50 yr (but not in women) approximate entropy was increased (0.942±0.301 vs. 1.258±0.267, P = 0.007) compared with younger men, as well as spikiness (0.363±0.122 vs. 0463±2.12, P = 0.031). Cosinor analysis disclosed higher mesor and amplitude in females than in men, but the acrophase was gender-independent. The acrophase was determined by age and BMI (R² = 0.186, P = 0.001).

Conclusion

In healthy adults, selective combinations of gender, age, and BMI specify distinct PRL dynamics, thus requiring balanced representation of these variables in comparative PRL studies.     

Is Human Cytomegalovirus Infection Associated with Hypertension? The United States National Health and Nutrition Examination Survey 1999–2002

Purpose

Recent studies have implicated the human cytomegalovirus (HCMV) as a possible pathogen for causing hypertension. We aimed to study the association between HCMV infection and hypertension in the United States National Health and Nutrition Examination Survey (NHANES).

Methods

We analyzed data on 2979 men and 3324 women in the NHANES 1999–2002. We included participants aged 16–49 years who had valid data on HCMV infection and hypertension.

Results

Of the participants, 54.7% had serologic evidence of HCMV infection and 17.5% had hypertension. There were ethnic differences in the prevalence of HCMV infection (P<0.001) and hypertension (P<0.001). The prevalence of both increased with age (P<0.001). Before adjustment, HCMV seropositivity was significantly associated with hypertension in women (OR = 1.63, 95% CI = 1.25–2.13, P = 0.001) but not in men. After adjustment for race/ethnicity, the association between HCMV seropositivity and hypertension in women remained significant (OR = 1.55, 95% CI = 1.20–2.02, P = 0.002). Further adjustment for body mass index, diabetes status and hypercholesterolemia attenuated the association (OR = 1.44, 95% CI = 1.10–1.90, P = 0.010). However, after adjusting for age, the association was no longer significant (OR = 1.24, 95% CI = 0.91–1.67, P = 0.162).

Conclusions

In this nationally representative population-based survey, HCMV seropositivity is associated with hypertension in women in the NHANES population. This association is largely explained by the association of hypertension with age and the increase in past exposure to HCMV with age.     

Erectile Dysfunction and Cardiovascular Events in Diabetic Men: A Meta-analysis of Observational Studies

Background

Several studies have shown that erectile dysfunction (ED) influences the risk of cardiovascular events (CV events). However, a meta-analysis of the overall risk of CV events associated with ED in patients with diabetes has not been performed.

Methodology/Principal Findings

We searched MEDLINE and the Cochrane Library for pertinent articles (including references) published between 1951 and April 22, 2012. English language reports of original observational cohort studies and cross-sectional studies were included. Pooled effect estimates were obtained by random effects meta-analysis.A total of 3,791 CV events were reported in 3 cohort studies and 9 cross-sectional studies (covering 22,586 subjects). Across the cohort studies, the overall odds ratio (OR) of diabetic men with ED versus those without ED was 1.74 (95% confidence interval [CI]: 1.34–2.27; P<0.001) for CV events and 1.72 (95% CI: 1.5–1.98; P<0.001) for coronary heart disease (CHD). The funnel plot, Begg''s test, and Egger''s test did not show evidence of publication bias (all P>0.05). Moreover, meta-regression analysis found no relationship between the method used to assess ED (questionnaire or interview), mean age, mean hemoglobin A_1c, mean body mass index, or mean duration of diabetes and the risk of CV events or CHD. In the cross-sectional studies, the OR of diabetic men with ED versus those without ED was 3.39 (95% CI: 2.58–4.44; P<0.001) for CV events (N = 9), 3.43 (95% CI: 2.46–4.77; P<0.001) for CHD (N = 7), and 2.63 (95% CI: 1.41–4.91; P = 0.002) for peripheral vascular disease (N = 5).

Conclusion/Significance

ED was associated with an increased risk of CV events in diabetic patients. Prevention and early detection of cardiovascular disease are important in the management of diabetes, especially in view of the rapid increase in its prevalence.     

Overexpression of the HIF hydroxylases PHD1, PHD2, PHD3 and FIH are individually and collectively unfavorable prognosticators for NSCLC survival

Introduction

Hypoxia induced factors (HIFs) are at the heart of the adaptive mechanisms cancer cells must implement for survival. HIFs are regulated by four hydroxylases; Prolyl hydroxylase (PHD)-1,-2,-3 and factor inhibiting HIF (FIH). We aimed to investigate the prognostic impact of these oxygen sensors in NSCLC.

Methods

Tumor tissue samples from 335 resected stages I to IIIA NSCLC patients was obtained and tissue microarrays (TMAs) were constructed. Hydroxylase expression was evaluated by immunohistochemistry.

Principal Findings

There was scorable expression for all HIF hydroxylases in tumor cells, but not in stroma. In univariate analyses, high tumor cell expression of all the HIF hydroxylases were unfavorable prognosticators for disease-specific survival (DSS); PHD1 (P = 0.023), PHD2 (P = 0.013), PHD3 (P = 0.018) and FIH (P = 0.033). In the multivariate analyses we found high tumor cell expression of PHD2 (HR = 2.03, CI 95% 1.20–3.42, P = 0.008) and PHD1 (HR = 1.45, CI 95% 1.01–2.10, P = 0.047) to be significant independent prognosticators for DSS. Besides, there was an additive prognostic effect by the increasing number of highly expressed HIF hydroxylases. Provided none high expression HIF hydroxylases, the 5-year survival was 80% vs. 23% if all four were highly expressed (HR = 6.48, CI 95% 2.23–18.8, P = 0.001).

Conclusions

HIF hydroxylases are, in general, poor prognosticators for NSCLC survival. PHD1 and PHD2 are independent negative prognostic factors in NSCLC. Moreover, there is an additive poor prognostic impact by an increasing number of highly expressed HIF hydroxylases.     

Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: Aruba

Objective

The aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.

Design

A case-control study of Aruban-born children (1990–2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (≤29, 30–39, 40–49, ≥50y). The analysis was made, using conditional logistic regression.

Results

Advanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (≤29y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.

Conclusion

This study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.     

A review of adult mortality due to 2009 pandemic (H1N1) influenza A in California

Background

While children and young adults had the highest attack rates due to 2009 pandemic (H1N1) influenza A (2009 H1N1), studies of hospitalized cases noted high fatality in older adults. We analyzed California public health surveillance data to better characterize the populations at risk for dying due to 2009 H1N1.

Methods and Findings

A case was an adult ≥20 years who died with influenza-like symptoms and laboratory results indicative of 2009 H1N1. Demographic and clinical data were abstracted from medical records using a standardized case report form. From April 3, 2009 – August 10, 2010, 541 fatal cases ≥20 years with 2009 H1N1 were reported. Influenza fatality rates per 100,000 population were highest in persons 50–59 years (3.5; annualized rate = 2.6) and 60–69 years (2.3; annualized rate = 1.7) compared to younger and older age groups (0.4–1.9; annualized rates = 0.3–1.4). Of 486 cases hospitalized prior to death, 441 (91%) required intensive care unit (ICU) admission. ICU admission rates per 100,000 population were highest in adults 50–59 years (8.6). ICU case-fatality ratios among adults ranged from 24–42%, with the highest ratios in persons 70–79 years. A total of 425 (80%) cases had co-morbid conditions associated with severe seasonal influenza. The prevalence of most co-morbid conditions increased with increasing age, but obesity, pregnancy and obstructive sleep apnea decreased with age. Rapid testing was positive in 97 (35%) of 276 tested. Of 482 cases with available data, 384 (80%) received antiviral treatment, including 49 (15%) of 328 within 48 hours of symptom onset.

Conclusions

Adults aged 50–59 years had the highest fatality due to 2009 H1N1; older adults may have been spared due to pre-existing immunity. However, once infected and hospitalized in intensive care, case-fatality ratios were high for all adults, especially in those over 60 years. Vaccination of adults older than 50 years should be encouraged.     

Impact of non-HIV and HIV risk factors on survival in HIV-infected patients on HAART: a population-based nationwide cohort study

Background

We determined the impact of three factors on mortality in HIV-infected patients who had been on highly active antiretroviral therapy (HAART) for at least one year: (1) insufficient response to (HAART) and presence of AIDS-defining diseases, (2) comorbidity, and (3) drug and alcohol abuse and compared the mortality to that of the general population.

Methodology/Principal Findings

In a Danish nationwide, population-based cohort study, we used population based registries to identify (1) all Danish HIV-infected patients who started HAART in the period 1 January 1998–1 July 2009, and (2) a comparison cohort of individuals matched on date of birth and gender (N = 2,267 and 9,068, respectively). Study inclusion began 1 year after start of HAART. Patients were categorised hierarchically in four groups according to the three risk factors, which were identified before study inclusion. The main outcome measure was probability of survival from age 25 to 65 years. The probability of survival from age 25 to age 65 was substantially lower in HIV patients [0.48 (95% confidence interval (CI) 0.42–0.55)] compared to the comparison cohort [0.88 (0.86 to 0.90)]. However, in HIV patients with no risk factors (N = 871) the probability of survival was equivalent to that of the general population [0.86 (95% CI 0.77–0.92)]. In contrast, the probability of survival was 0.58 in patients with HIV risk factors (N = 704), 0.30 in patients with comorbidities (N = 479), and 0.03 in patients with drug or alcohol abuse (N = 313).

Conclusions

The increased risk of death in HIV-infected individuals is mainly attributable to risk factors that can be identified prior to or in the initial period of antiretroviral treatment. Mortality in patients without risk factors on a successful HAART is almost identical to that of the non–HIV-infected population.     

Receptor activator of NF-kB (RANK) expression in primary tumors associates with bone metastasis occurrence in breast cancer patients

Background

Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG.

Materials and Methods

We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival.

Results

Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that “RANK-negative” and “RANK-positive” patients had a SDFS of 105.7 months (95% CI: 73.9–124.4) and 58.9 months (95% CI: 34.7–68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029).

Conclusions

This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.     

First efficacy results of capecitabine with anthracycline- and taxane-based adjuvant therapy in high-risk early breast cancer: a meta-analysis

Background

Capecitabine is effective and indicated for the salvage treatment of metastatic breast cancer. Therefore, it is essential to evaluate the efficacy of capecitabine in the adjuvant setting. There have been two large randomized studies to determine whether patients with high-risk early breast cancer benefit from the addition of capecitabine to standard chemotherapy, but they have yielded inconsistent results. We first undertook a meta-analysis to evaluate the efficacy of the addition of capecitabine over standard treatment.

Methods

PubMed, EBSCO, Web of Science, conference proceedings and key trials were searched from 1998 to 2011. The hazard ratio (HR) was used to evaluate the efficacy of a taxane-anthracycline regimen and a taxane-anthracycline-capecitabine regimen in early breast cancer. All of the data from each study use either fixed-effects or random-effects by Stata.

Findings

We found significant improvement in the additional capecitabine arm versus control in disease-free survival (DFS) (HR = 0.83, 95% CI: 0.71–0.98, P = 0.027), overall survival (OS) (HR = 0.71, 95% CI: 0.57–0.88, P = 0.002), distant recurrence (HR = 0.79, 95% CI: 0.66–0.94, P = 0.008) and the death from breast cancer only (HR = 0.65, 95% CI: 0.51–0.83, P = 0.001). Meanwhile, the subgroup analysis revealed that capecitabine improved the DFS in triple negative (HR = 0.71, 95% CI: 0.53–0.96, P = 0.028), hormone receptor negative (HR = 0.73, CI: 0.56–0.94, P = 0.017) and HER2 negative (HR = 0.81, CI: 0.67–0.98, P = 0.034) patients.

Conclusion

Due to the synergistic effect of taxane and capecitabine, taxane-anthracycline-capecitabine regimen may effectively improve the efficacy in the adjuvant setting and may be a novel generation of adjuvant chemotherapy regimen. The results of the current meta-analysis support this hypothesis and indicate that taxane-based regimen with capecitabine may be an effective, convenient, and well tolerated regimen in patients with early breast cancer.     

Ocular Axial Length and Its Associations in Chinese: The Beijing Eye Study

Purpose

To investigate the normative data of ocular axial length and its associations in Chinese.

Method

The population-based Beijing Eye Study 2011 is a cross-sectional study performed in Greater Beijing. The study included 3468 individuals (1963 (56.6%) women) with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic and medical examination was performed. Axial length was measured by optical low-coherence reflectometry.

Results

Axial length measurements were available for 3159 (91.1%) study participants. Mean axial length was 23.25±1.14 mm (range: 18.96–30.88 mm). In multivariate analysis, axial length was significantly associated with the systemic parameters of higher age (P<0.001), higher body height (P = 0.003), higher level of education (P<0.001) and urban region of habitation (P<0.001), and with the ocular parameters of thicker central cornea (P = 0.001), higher corneal curvature radius (P<0.001), deeper anterior chamber (P<0.001), thicker lens (P<0.001), more myopic refractive error (P<0.001), larger pupil diameter (P = 0.018), and higher best corrected visual acuity (P<0.001). It was additionally and negatively associated with the lens vault (P<0.001). In highly myopic eyes, axial length was significantly associated with lower level of education (P = 0.008), more myopic refractive error (P<0.001), and lower best corrected visual acuity (P = 0.034).

Conclusions

Mean ocular axial length in the older adult population of Greater Beijing (23.25±1.14 mm) was similar to the value measured in other urban populations and was higher than in a rural Central Indian population. The association between axial length and older age may potentially be associated with a survival artifact. The association between axial length and body height agrees with the general association between anthropomorphic measures and eye globe size. The association with the level of education and urban region of habitation confirms with previous studies. In contrast in highly myopic eyes, axial length was negatively associated with educational level and best corrected visual acuity.     

Activated TLR signaling in atherosclerosis among women with lower Framingham risk score: the multi-ethnic study of atherosclerosis

Background

Atherosclerosis is the leading cause of cardiovascular disease (CVD). Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis.

Results

A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-Ethnic Study of Atherosclerosis cohort aged 50 or above. All participants had low (<10%) to intermediate (10% to 20%) predicted Framingham risk; cases (N = 48) had coronary artery calcium (CAC) score >100 and carotid intima-media thickness (IMT) >1.0 mm, whereas controls (N = 71) had CAC<10 and IMT <0.65 mm. We identified two major expression profiles significantly associated with significant atherosclerosis (odds ratio 4.85; P<0.001); among those with Framingham risk score <10%, the odds ratio was 5.30 (P<0.001). Ontology analysis of the gene signature reveals activation of a major innate immune pathway, toll-like receptors and IL-1R signaling, in individuals with significant atherosclerosis.

Conclusion

Gene expression profiles of peripheral blood may be a useful tool to identify individuals with significant burden of atherosclerosis, even among those with low predicted risk by clinical factors. Furthermore, our data suggest an intimate connection between atherosclerosis and the innate immune system and inflammation via TLR signaling in lower risk individuals.     

Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: a sub-group and cohort study

Background and Objective

Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery.

Methods

An observational cohort study was performed on consecutive patients (n = 1879) receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome - major adverse cardiocerebral events (MACE) that include permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest.

Results

Of all patients, 1145 patients met the inclusion criteria and were divided into two groups: those taking (n = 858) or not taking (n = 287) aspirin within 5 days preceding surgery. Patients with aspirin presented significantly more with history of hypertension, diabetes, peripheral arterial disease, previous MI, angina and older age. With propensity scores adjusted and multivariate logistic regression, however, this study showed that preoperative aspirin therapy (vs. no aspirin) significantly reduced the risk of MACE (8.4% vs. 12.5%, odds ratio [OR] 0.585, 95% CI 0.355–0.964, P = 0.035), postoperative renal failure (2.6% vs. 5.2%, OR 0.438, CI 0.203–0.945, P = 0.035) and dialysis required (0.8% vs. 3.1%, OR 0.230, CI 0.071–0.742, P = 0.014), but did not significantly reduce 30-day mortality (4.1% vs. 5.8%, OR 0.744, CI 0.376–1.472, P = 0.396) nor it increased readmissions in the patients undergoing cardiac surgery.

Conclusions

Preoperative aspirin therapy is associated with a significant decrease in the risk of MACE and renal failure and did not increase readmissions in patients undergoing non-emergent cardiac surgery.     

Association of age with mortality and virological and immunological response to antiretroviral therapy in rural South African adults

Objective

To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort.

Design

Retrospective cohort analysis using data from a public HIV Treatment & Care Programme.

Methods

Adults initiating ART 1^st August 2004 - 31^st October 2009 were stratified by age at initiation: young adults (16–24 years) mid-age adults (25–49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points.

Results

8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25–49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90–7.78); 6.55 (95% CI 6.11–7.02) and 8.69 (95% CI 7.34–10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0–3 months (MR: 27.1 vs 17.17 and 21.36) and 3–12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0–3 months) whilst immunological and virological responses were associated with mortality after 12months.

Conclusions

Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART.     

Prognostic impacts of angiopoietins in NSCLC tumor cells and stroma: VEGF-A impact is strongly associated with Ang-2

Introduction

Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor Tie-2, as well as their relation to the prognostic expression of VEGF-A.

Methods

335 unselected stage I-IIIA NSCLC-patients were included and tissue samples of respective tumor cells and stroma were collected in tissue microarrays (TMAs). Immunohistochemistry (IHC) was used to semiquantitatively evaluate the expression of markers in duplicate tumor and stroma cores.

Principal Findings

In univariate analyses, low tumor cell expression of Ang-4 (P = 0.046) and low stromal expressions of Ang-4 (P = 0.009) and Ang-2 (P = 0.017) were individually associated with a poor survival. In the multivariate analysis, low stromal Ang-2 (HR 1.88; CI 95% 1.15-3.08) and Ang-4 (HR 1.47, CI 95% 1.02–2.11, P = 0.04) expressions were independently associated with a poor prognosis. In patients with high tumor cell expression of Ang-2, a concomitantly high tumor VEGF-A expression mediated a dramatic survival reduction (P<0.001). In the multivariate analysis of patients with high Ang-2 expression, high tumor VEGF-A expression appeared an independent poor prognosticator (HR 6.43; CI 95% 2.46–16.8; P<0.001).

Conclusions

In tumor cells, only Ang-4 expression has prognostic impact in NSCLC. In tumor stroma, Ang-4 and Ang-2 are independently associated with survival. The prognostic impact of tumor cell VEGF-A in NSCLC appears strongly associated with a concomitantly high tumor cell expression of Ang-2.     

Estimation of daily energy expenditure in pregnant and non-pregnant women using a wrist-worn tri-axial accelerometer

Background

Few studies have compared the validity of objective measures of physical activity energy expenditure (PAEE) in pregnant and non-pregnant women. PAEE is commonly estimated with accelerometers attached to the hip or waist, but little is known about the validity and participant acceptability of wrist attachment. The objectives of the current study were to assess the validity of a simple summary measure derived from a wrist-worn accelerometer (GENEA, Unilever Discover, UK) to estimate PAEE in pregnant and non-pregnant women, and to evaluate participant acceptability.

Methods

Non-pregnant (N = 73) and pregnant (N = 35) Swedish women (aged 20–35 yrs) wore the accelerometer on their wrist for 10 days during which total energy expenditure (TEE) was assessed using doubly-labelled water. PAEE was calculated as 0.9×TEE-REE. British participants (N = 99; aged 22–65 yrs) wore accelerometers on their non-dominant wrist and hip for seven days and were asked to score the acceptability of monitor placement (scored 1 [least] through 10 [most] acceptable).

Results

There was no significant correlation between body weight and PAEE. In non-pregnant women, acceleration explained 24% of the variation in PAEE, which decreased to 19% in leave-one-out cross-validation. In pregnant women, acceleration explained 11% of the variation in PAEE, which was not significant in leave-one-out cross-validation. Median (IQR) acceptability of wrist and hip placement was 9(8–10) and 9(7–10), respectively; there was a within-individual difference of 0.47 (p<.001).

Conclusions

A simple summary measure derived from a wrist-worn tri-axial accelerometer adds significantly to the prediction of energy expenditure in non-pregnant women and is scored acceptable by participants.     

An accurate definition of the status of inactive hepatitis B virus carrier by a combination of biomarkers (FibroTest-ActiTest) and viral load

Background

The combination of transaminases (ALT), biopsy, HBeAg and viral load have classically defined the inactive status of carriers of chronic hepatitis B. The use of FibroTest (FT) and ActiTest (AT), biomarkers of fibrosis and necroinflammatory activity, has been previously validated as alternatives to biopsy. We compared the 4-year prognostic value of combining FT-AT and viral load for a better definition of the inactive carrier status.

Methods and Findings

1,300 consecutive CHB patients who had been prospectively followed since 2001 were pre-included. The main endpoint was the absence of liver-related complications, transplantation or death. We used the manufacturers'' definitions of normal FT (< = 0.27), normal AT (< = 0.29) and 3 standard classes for viral load. The adjustment factors were age, sex, HBeAg, ethnic origin, alcohol consumption, HIV-Delta-HCV co-infections and treatment.

Results

1,074 patients with baseline FT-AT and viral load were included: 41 years old, 47% African, 27% Asian, 26% Caucasian. At 4 years follow-up, 50 complications occurred (survival without complications 93.4%), 36 deaths occurred (survival 95.0%), including 27 related to HBV (survival 96.1%). The prognostic value of FT was higher than those of viral load or ALT when compared using area under the ROC curves [0.89 (95%CI 0.84–0.93) vs 0.64 (0.55–0.71) vs 0.53 (0.46–0.60) all P<0.001], survival curves and multivariate Cox model [regression coefficient 5.2 (3.5–6.9; P<0.001) vs 0.53 (0.15–0.92; P = 0.007) vs −0.001 (−0.003−0.000;P = 0.052)] respectively. A new definition of inactive carriers was proposed with an algorithm combining “zero” scores for FT-AT (F0 and A0) and viral load classes. This new algorithm provides a 100% negative predictive value for the prediction of liver related complications or death. Among the 275 patients with the classic definition of inactive carrier, 62 (23%) had fibrosis presumed with FT, and 3 died or had complications at 4 year.

Conclusion

In patients with chronic hepatitis B, a combination of FibroTest-ActiTest and viral load testing accurately defined the prognosis and the inactive carrier status.     

Cesarean Section Rates and Indications in Sub-Saharan Africa: A Multi-Country Study from Medecins sans Frontieres

Objectives

The World Health Organization considers Cesarean section rates of 5–15% to be the optimal range for targeted provision of this life saving intervention. However, access to safe Cesarean section in resource-limited settings is much lower, estimated at 1–2% reported in sub-Saharan Africa. This study reports Cesarean sections rates and indications in Democratic Republic of Congo, Burundi, and Sierra Leone, and describe the main parameters associated with maternal and early neonatal mortality.

Methods

Women undergoing Cesarean section from August 1 2010 to January 31 2011 were included in this prospective study. Logistic regression was used to model determinants of maternal and early neonatal mortality.

Results

1276 women underwent a Cesarean section, giving a frequency of 6.2% (range 4.1–16.8%). The most common indications were obstructed labor (399, 31%), poor presentation (233, 18%), previous Cesarean section (184, 14%), and fetal distress (128, 10%), uterine rupture (117, 9%) and antepartum hemorrhage (101, 8%). Parity >6 (adjusted odds ratio [aOR] = 8.6, P = 0.015), uterine rupture (aOR = 20.5; P = .010), antepartum hemorrhage (aOR = 13.1; P = .045), and pre-eclampsia/eclampsia (aOR = 42.9; P = .017) were associated with maternal death. Uterine rupture (aOR = 6.6, P<0.001), anterpartum hemorrhage (aOR = 3.6, P<0.001), and cord prolapse (aOR = 2.7, P = 0.017) were associated with early neonatal death.

Conclusions

This study demonstrates that target Cesarean section rates can be achieved in sub-Saharan Africa. Identifying the common indications for Cesarean section and associations with mortality can target improvements in antenatal services and emergency obstetric care.     

Heart failure and preserved left ventricular function: long term clinical outcome

Background

Patients with heart failure (HF) have a poor prognosis. The proportion of patients with HF and preserved left ventricular function (LVF) is increasing. Long term prognosis of HF with preserved LVF may not be so benign.

Objectives

To evaluate the long term clinical outcome of patients with HF and preserved LVF and predictors of outcome.

Methods

We prospectively evaluated 309 patients hospitalized with a definite clinical diagnosis of HF. Patients were followed for a mean of 6.5 years for clinical outcome.

Results

More than a third (36%) of the patients had preserved systolic LVF based on echocardiography. The long term survival rate in this group was poor and not significantly different from patients with reduced LVF (28% vs 23% respectively, P = 0.2). The adjusted survival rate by Cox regression analysis was also not significantly different (hazard ratio 1.16, 95% confidence interval 0.87–1.55, P = 0.31). The event free survival from death or heart failure re-hospitalization was also low in both groups and not significantly different between patients with preserved vs. reduced LVF (12% vs. 10% respectively, P = 0.2). Predictors of mortality in patients with preserved LVF were age, functional capacity and serum urea levels.

Conclusions

The long term clinical outcome of patients with heart failure and preserved LVF is poor and not significantly different from patients with reduced LVF.     

The -2518A/G Polymorphism in the MCP-1 Gene and Tuberculosis Risk: A Meta-Analysis

Background

The -2518A/G polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene has been implicated in the susceptibility to tuberculosis (TB), but the results are not conclusive. The aim of this study is to investigate the association between the -2518A/G polymorphism in the MCP-1 gene and the risk of tuberculosis by meta-analysis.

Methods

We searched Pubmed, Embase, CNKI and Wanfang databases, covering all studies until April 29^th, 2011. Statistical analyses were performed using the Revman4.2 and STATA10.0 software.

Results

A total of 5341 cases and 6075 controls in 13 case-control studies were included in the meta-analysis. The results indicated that the GG homozygote carriers had a 67% increased risk of TB compared with the A allele carriers (GG vs. GA+AA: OR = 1.67, 95%CI = 1.25–2.23, P = 0.0006). In the subgroup analysis by ethnicity, significant elevated risks were found in Asians and Latinos, but not in Africans (GG vs. GA+AA: OR = 1.79, 95%CI = 1.19–2.70 and P = 0.005 for Asians; OR = 2.15, 95%CI = 1.32–3.51 and P = 0.002 for Latinos; OR = 1.28, 95%CI = 0.45–3.64 and P = 0.65 for Africans).

Conclusion

This meta-analysis suggested that the -2518A/G polymorphism of MCP-1 gene would be a risk factor for TB in Asians and Latinos, while not in Africans.