Preoperative HO-1 Levels as Prognostic Factor for Adverse Cardiac Events in Elder Patients Undergoing Non-Cardiac Surgery

Background

Hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1(HO-1) are involved in the tissue hypoxic response.

Hypothesis

HIF-1α and HO-1 levels may predict cardiac ischemia and adverse cardiac events during non-cardiac surgery.

Methods

HIF-1α and HO-1 levels were determined in elderly patients undergoing non-cardiac surgery preoperatively and at 30 minutes, 48 and 72 hours postoperatively. Results were analyzed with respect to the occurrence of adverse cardiac events.

Results

A total of 380 patients with a mean age of 65.3 years were included, and 54 (14.2%) who had adverse cardiac events during or after the surgery. HIF-1α and HO-1 levels in the adverse cardiac event group were significantly higher than in the group without adverse cardiac events at each time point (all, P<0.05). In multivariates regression analysis, the odds of an adverse cardiac event was increased by every 1-year increase in age (odd ratio [OR] 1.39, P<0.001), abnormal ECG at baseline (OR 2.27, P = 0.048), myocardial infarction history (OR 3.18, P = 0.015), and positive baseline cTnI level were associated with an increased likelihood of an adverse cardiac event (OR 8.78, P = 0.019), and for every 1 unit increase of HO-1, the odds of an adverse cardiac event increased by 1.30 (P = 0.002).

Conclusion

Determination of preoperative HO-1 levels may aid in identifying patients at risk of developing ischemic cardiac events.     

Ocular Dominance Is Associated with the Ganglion Cell-Inner Plexiform Layer Thickness Profile in the Macula

Purpose

To investigate the characteristics of macular ganglion cell-inner plexiform layer (GCIPL) thickness profiles associated with ocular dominance.

Setting

Private practice, Seoul, Republic of Korea.

Design

Comparative case-control study.

Methods

Both eyes of 199 participants with no ophthalmic abnormalities were included. Participants were imaged by spectral-domain optical coherence tomography, and underwent dominant eye testing using a hole-in-a-card test (sighting dominance) at the same visit. Macular GCIPL, as well as circumpapillary retinal nerve fiber layer (RNFL) thickness were compared for individual patients, according to ocular dominance.

Results

Ocular dominance occurred predominantly in the right eye (right vs. left: 72.36 vs. 27.60%; P < 0.001). In the comparison of macular GCIPL thickness, the average (81.27±5.01 μm vs. 80.66±6.31 μm in dominant vs. non-dominant eyes), inferonasal (81.39±5.47μm vs. 80.33±6.82μm, and inferior sectors (77.95±6.05μm vs. 76.97±8.15μm) were significantly different between dominant and non-dominant eyes (P = 0.040, 0.005, and 0.032, respectively). Significant predictors of average GCIPL thickness were spherical equivalent (β = 1.37, P<0.001), astigmatic power (β = 1.44, P = 0.009), disc area (β = 3.90, P < 0.001), average RNFL thickness (β = 0.22, P<0.001), average cup-to-disc ratio (β = 5.74, P = 0.002), difference between the inferior and superior quadrant RNFL thicknesses (β = 0.08, P = 0.024), and ocular dominance (β = 2.10, P = 0.020). On multivariate regression analysis, ocular dominance was correlated with average GCIPL thickness after adjusting for potential confounders (β = 1.63, P = 0.048).

Conclusions

Dominant eyes accompanied significantly thicker average macular GCIPL. This information suggests that macular GCIPL thickness may provide an indicator of the relative dominance of an eye.     

Associations between TNF-α Polymorphisms and Pneumonia: A Meta-Analysis

Background

Several studies evaluated the associations of tumor necrosis factor-α (TNF-α) polymorphisms with pneumonia in different populations. However, the results were conflicting and controversial.

Methods

Databases including PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Data were extracted independently by two investigators. Crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated.

Results

Twelve case-control studies and one cohort study were included. Overall, no association between TNF-α −308A/G polymorphism and pneumonia risk was observed for AA +AG vs. GG (OR = 1.13; 95% CI 0.99–1.30; P = 0.07). In addition, TNF-α −308A/G polymorphism was not associated with pneumonia mortality (OR = 1.96; 95% CI 0.94–4.09; P = 0.07). Furthermore, there was no association of TNF-α −238A/G polymorphism with the risk of pneumonia (OR = 1.38; 95% CI 0.84–2.28; P = 0.20).

Conclusions

TNF-α −308A/G, −238A/G polymorphisms were not associated with pneumonia risk. Moreover, TNF-α −308A/G polymorphism did not play a role in the pneumonia mortality risk.     

Tumor necrosis factor inhibitor therapy but not standard therapy is associated with resolution of erosion in the sacroiliac joints of patients with axial spondyloarthritis

Introduction

Radiography is an unreliable and insensitive tool for the assessment of structural lesions in the sacroiliac joints (SIJ). Magnetic resonance imaging (MRI) detects a wider spectrum of structural lesions but has undergone minimal validation in prospective studies. The Spondyloarthritis Research Consortium of Canada (SPARCC) MRI Sacroiliac Joint (SIJ) Structural Score (SSS) assesses a spectrum of structural lesions (erosion, fat metaplasia, backfill, ankylosis) and its potential to discriminate between therapies requires evaluation.

Methods

The SSS score assesses five consecutive coronal slices through the cartilaginous portion of the joint on T1-weighted sequences starting from the transitional slice between cartilaginous and ligamentous portions of the joint. Lesions are scored dichotomously (present/absent) in SIJ quadrants (fat metaplasia, erosion) or halves (backfill, ankylosis). Two readers independently scored 147 pairs (baseline, 2 years) of scans from a prospective cohort of patients with SpA who received either standard (n = 69) or tumor necrosis factor alpha (TNFα) inhibitor (n = 78) therapy. Smallest detectable change (SDC) was calculated using analysis of variance (ANOVA), discrimination was assessed using Guyatt’s effect size, and treatment group differences were assessed using t-tests and the Mann–Whitney test. We identified baseline demographic and structural damage variables associated with change in SSS score by univariate analysis and analyzed the effect of treatment by multivariate stepwise regression adjusted for severity of baseline structural damage and demographic variables.

Results

A significant increase in mean SSS score for fat metaplasia (P = 0.017) and decrease in mean SSS score for erosion (P = 0.017) was noted in anti-TNFα treated patients compared to those on standard therapy. Effect size for this change in SSS fat metaplasia and erosion score was moderate (0.5 and 0.6, respectively). Treatment and baseline SSS score for erosion were independently associated with change in SSS erosion score (β = 1.75, P = 0.003 and β = 0.40, P < 0.0001, respectively). Change in ASDAS (β = −0.46, P = 0.006), SPARCC MRI SIJ inflammation (β = −0.077, P = 0.019), and baseline SSS score for fat metaplasia (β = 0.085, P = 0.034) were independently associated with new fat metaplasia.

Conclusion

The SPARCC SSS method for assessment of structural lesions has discriminative capacity in demonstrating significantly greater reduction in erosion and new fat metaplasia in patients receiving anti-TNFα therapy.     

Effect of Serum Leptin on Weight Gain Induced by Olanzapine in Female Patients with Schizophrenia

Background

Olanzapine (OLZ) treatment is associated with a high risk of weight gain, and may cause abnormalities in glycolipid metabolism. Therefore, the underlying mechanism of OLZ-related weight gain is needed to clarify but not yet been adequately determined. In recent years, adipocytokines such as leptin, adiponectin, and tumor necrosis factor (TNF)-α, which play important roles in energy homeostasis, have been suggested as biomarkers of weight gain. Here, we determined if baseline plasma concentrations of leptin, adiponectin, and TNF-α predict weight gain following OLZ treatment.

Methods

We recruited 31 schizophrenia outpatients (12 men and 19 women, 28.8 ± 10.2 years old) that were unmedicated or on another antipsychotic monotherapy medication. Baseline body mass index (BMI) and plasma levels of leptin, adiponectin, and TNF-α were obtained. All patients started or were switched to OLZ monotherapy for a maximum of 1 year. BMI was also obtained at the endpoint.

Results

Mean BMI change following OLZ treatment was 2.1 ± 2.7 kg/m². BMI change from baseline to endpoint negatively-correlated with baseline leptin levels in female patients (r = −0.514, P = 0.024), but not male patients. Baseline adiponectin or TNF-α levels were not correlated with BMI change.

Conclusion

Baseline plasma leptin can have an effect on subsequent weight gain following OLZ treatment in female patients with schizophrenia.     

Comparison of Baseline versus Posttreatment Left Ventricular Ejection Fraction in Patients with Acute Decompensated Heart Failure for Predicting Cardiovascular Outcome: Implications from Single-Center Systolic Heart Failure Cohort

Aims

The prognostic values of left ventricular ejection fraction (LVEF) during heart failure (HF) with acute decompensation or after optimal treatment have not been extensively studied. We hypothesized that posttreatment LVEF has superior predictive value for long-term prognosis than LVEF at admission does.

Methods and Results

In Protocol 1, 428 acute decompensated HF (ADHF) patients with LVEF ≤35% in a tertiary medical center were enrolled and followed for a mean period of 34.7 ± 10.8 months. The primary and secondary end points were all-cause mortality and HF readmission, respectively. In total, 86 deaths and 240 HF readmissions were recorded. The predictive values of baseline LVEF at admission and LVEF 6 months posttreatment were analyzed and compared. The posttreatment LVEFs were predictive for future events (P = 0.01 for all-cause mortality, P < 0.001 for HF readmission), but the baseline LVEFs were not. In Protocol 2, the outcomes of patients with improved LVEF (change of LVEF: ≥+10%), unchanged LVEF (change of LVEF: –10% to +10%), and reduced LVEF (change of LVEF: ≤–10%) were analyzed and compared. Improved LVEF occurred in 171 patients and was associated with a superior long-term prognosis among all groups (P = 0.02 for all-cause mortality, P < 0.001 for HF readmission). In Protocol 3, independent predictors of improved LVEF were analyzed, and baseline LV end-diastolic dimension (LVEDD) was identified as a powerful predictor in ADHF patients (P < 0.001).

Conclusions

In patients with ADHF, posttreatment LVEF but not baseline LVEF had prognostic power. Improved LVEF was associated with superior long-term prognosis, and baseline LVEDD identified patients who were more likely to have improved LVEF. Therefore, baseline LVEF should not be considered a relevant prognosis factor in clinical practice for patients with ADHF.     

RGD-Targeted Ultrasound Contrast Agent for Longitudinal Assessment of Hep-2 Tumor Angiogenesis In Vivo

Objective

To prepare arginine-glycine-aspartate (RGD)-targeted ultrasound contrast microbubbles (MBs) and explore the feasibility of their use in assessing dynamic changes in αvβ3 integrin expression in a murine model of tumor angiogenesis.

Methods

RGD peptides were conjugated to the surfaces of microbubbles via biotin-avidin linkage. Microbubbles bearing RADfK peptides were prepared as controls. The RGD-MBs were characterized using an Accusizer 780 and optical microscopy. The binding specificity of the RGD-MBs for ανβ3-expressing endothelial cells (bEnd.3) was demonstrated in vitro by a competitive inhibition experiment. In an in vivo study, mice bearing tumors of three different stages were intravenously injected with RGD-MBs and subjected to targeted, contrast-enhanced, high-frequency ultrasound. Subsequently, tumors were harvested and sectioned for immunofluorescence analysis of ανβ3 expression.

Results

The mean size of the RGD-MBs was 2.36 ± 1.7 μm. The RGD-MBs showed significantly higher adhesion levels to bEnd.3 cells compared to control MBs (P < 0.01). There was rarely binding of RGD-MBs to αvβ3-negative MCF-7 cells. Adhesion of the RGD-MBs to the bEnd.3 cells was significantly inhibited following treatment with anti-alpha(v) antibodies. The quantitative acoustic video intensity for high-frequency, contrast-enhanced ultrasound imaging of subcutaneous human laryngeal carcinoma (Hep-2) tumor xenografts was significantly higher in small tumors (19.89 ± 2.49) than in medium tumors (11.25 ± 2.23) and large tumors (3.38 ± 0.67) (P < 0.01).

Conclusions

RGD-MBs enable noninvasive in vivo visualization of changes in tumor angiogenesis during tumor growth in subcutaneous cancer xenografts.     

γδ T Cells Are Involved in Acute HIV Infection and Associated with AIDS Progression

Background

Early diagnosis is vital to HIV control. γδ T cells play critical roles in viral infections, but their activation in acute HIV infected patients and follow up to 18 months has not been described.

Methods

Changes in γδ T cells, including subsets, function and activation, in treated and untreated acutely HIV-infected patients (n = 79) were compared by cytotoxicity assay and flow cytometry with healthy controls (n = 21) at month 0, 6, 12 and 18.

Results

In acutely HIV-infected patients, Vδ1 cell proportion was elevated (P = 0.027) with Vδ2 population reduced (P = 0.002). Effector and central memory γδ T cell factions were decreased (P = 0.006 and P = 0.001, respectively), while proportion of terminal γδ T cells increased (P = 0.002). γδ T cell cytotoxicity was compromised over time. Fraction of IL-17-producing cells increased (P = 0.008), and IFN-γ-producing cells were unaffected (P = 0.115). Elevation of a microbial translocation marker, sCD14, was associated with γδ T cell activation (P = 0.001), which increased in a time-dependent manner, correlating with CD4/CD8 T cell activation set-points and CD4 counts. Antiretroviral therapy did not affect these changes.

Conclusions

γδ T cell subpopulation and functions change significantly in acute HIV infection and over time. Early γδ T cell activation was associated with CD4/CD8 T cell activation set-points, which predict AIDS progression. Therefore, γδ T cell activation represents a potential surrogate marker of AIDS progression.     

The Role of Cryptococcus in the Immune System of Pulmonary Cryptococcosis Patients

Objectives

To investigate the role of Cryptococcus in the immune system of immunocompetent patients with pulmonary cryptococcosis (PC) by analysing the dynamic changes of patients’ immune status before and after antifungal therapy.

Methods

The level of the serum interferon-γ (IFN-γ) and interleukin (IL)-2, -4, -10 and -12 was measured before and after 6-months of treatment. Peripheral blood samples were obtained from 30 immunocompetent PC patients and 30 age- and gender-matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated and incubated with recombinant human IL-12 (rhIL-12) for 48 h. Then the concentrations of IFN-γ and IL-4 in the supernatant were analysed.

Results

Baseline serum IFN-γ level was significantly lower in the PC patients as compared with the control group (P < 0.001). The serum IL-2 and IFN-γ of PC patients were significantly increased after appropriate treatments (P < 0.05 and P < 0.001 when compared to their baseline levels). The productions of IFN-γ in the culture supernatant of PBMCs showed no significant difference between the control and PC patients both before and after antifungal treatments. RhIL-12 is a potent stimulus for IFN-γ production. Culture PBMCs collected from PC patients before treatments had a smaller increase of IFN-γ production in the present of rhIL-12 than the control (P < 0.01); PBMCs from PC patients completing 6-months of treatment showed a comparable increase of IFN-γ production by rhIL-12 stimulation to the control group.

Conclusions

In apparently immunocompetent patients with PC, a normalization of serum IFN-γ was achieved after recovery from infection. This suggests that Cryptococcus infection per se can suppress the immune system and its elimination contributes to the reestablishment of an immune equilibrium.     

The Features of Inflammation Factors Concentrations in Aqueous Humor of Polypoidal Choroidal Vasculopathy

Purpose

To investigate the cytokine concentrations in the aqueous humor of patients with refractory polypoidal choroidal vasculopathy (PCV).

Methods

Three separate groups of patients were studied–refractory PCV (Group A, 41 eyes), stable PCV (Group B, 39 eyes) and senile cataract (Group C, 44 eyes). Aqueous humor samples were collected at two time points for Groups A and B–before the first intravitreal ranibizumab injection and before the last injection. Aqueous humor samples were collected prior to phacoemulsification in Group C. The cytokine concentrations of interleukin 2, 6, and 8 (IL-2, IL-6, and IL-8), tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and vascular endothelial growth factor (VEGF) were measured by cytometric bead array and flow cytometry.

Results

Before the first treatment, the MCP-1, VEGF, and TNF-α levels in Group A were significantly higher than those in Group C (P < 0.05), and the MCP-1 and VEGF levels in Group A were significantly higher than those in Group B (P < 0.05). Significantly higher MCP-1 and VEGF levels were seen in Group B compared to Group C (P < 0.05). Before the final treatment, the MCP-1, VEGF, and TNF-α concentrations in Group A were significantly higher than those in Group B (P < 0.05) and Group C (P < 0.05). IL-2 levels were significantly lower in Group A compared to Group B (P < 0.05) and Group C (P < 0.05).

Conclusion

Inflammatory cytokines such as MCP-1, VEGF, and TNF-α may be associated with the pathogenesis of both stable and refractory PCV.     

Clinicopathological Correlation and Prognostic Significance of Protein Kinase Cα Overexpression in Human Gastric Carcinoma

Objectives

This study investigated the PKCα protein expression in gastric carcinoma, and correlated it with clinicopathological parameters. The prognostic significance of PKCα protein expression in gastric carcinoma was analyzed.

Methods

Quantitative real-time PCR test was applied to compare the PKCα mRNA expression in tumorous and nontumorous tissues of gastric carcinoma in ten randomly selected cases. Then PKCα protein expression was evaluated in 215 cases of gastric carcinoma using immunohistochemical method. The immunoreactivity was scored semiquantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely PKCα overexpression group with score 2 or 3, and non-overexpression group with score 0 or 1. The PKCα protein expression was correlated with clinicopathological parameters. Survival analysis was performed to determine the prognostic significance of PKCα protein expression in patients with gastric carcinoma.

Results

PKCα mRNA expression was upregulated in all ten cases of gastric carcinoma via quantitative real-time PCR test. In immunohistochemical study, eighty-eight out of 215 cases (41%) of gastric carcinoma revealed PKCα protein overexpression, which was statistically correlated with age (P = 0.0073), histologic type (P<0.0001), tumor differentiation (P = 0.0110), depth of invasion (P = 0.0003), angiolymphatic invasion (P = 0.0373), pathologic stage (P = 0.0047), and distant metastasis (P = 0.0048). We found no significant difference in overall and disease free survival rates between PKCα overexpression and non-overexpression groups (P = 0.0680 and 0.0587). However, PKCα protein overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 0.632, P = 0.0415).

Conclusions

PKCα protein is upregulated in gastric carcinoma. PKCα protein expression is statistically correlated with age, histologic type, tumor differentiation, depth of invasion, angiolymphatic invasion, pathologic stage, and distant metastasis. The PKCα protein overexpression in patients with gastric carcinoma is a significant independent prognostic factor in multivariate Cox regression analysis.     

Is Quality and Completeness of Reporting of Systematic Reviews and Meta-Analyses Published in High Impact Radiology Journals Associated with Citation Rates?

Purpose

The purpose of this study is to determine whether study quality and completeness of reporting of systematic reviews (SR) and meta-analyses (MA) published in high impact factor (IF) radiology journals is associated with citation rates.

Methods

All SR and MA published in English between Jan 2007–Dec 2011, in radiology journals with an IF >2.75, were identified on Ovid MEDLINE. The Assessing the Methodologic Quality of Systematic Reviews (AMSTAR) checklist for study quality, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for study completeness, was applied to each SR & MA. Each SR & MA was then searched in Google Scholar to yield a citation rate. Spearman correlation coefficients were used to assess the relationship between AMSTAR and PRISMA results with citation rate. Multivariate analyses were performed to account for the effect of journal IF and journal 5-year IF on correlation with citation rate. Values were reported as medians with interquartile range (IQR) provided.

Results

129 studies from 11 journals were included (50 SR and 79 MA). Median AMSTAR result was 8.0/11 (IQR: 5–9) and median PRISMA result was 23.0/27 (IQR: 21–25). The median citation rate for SR & MA was 0.73 citations/month post-publication (IQR: 0.40–1.17). There was a positive correlation between both AMSTAR and PRISMA results and SR & MA citation rate; ρ=0.323 (P=0.0002) and ρ=0.327 (P=0.0002) respectively. Positive correlation persisted for AMSTAR and PRISMA results after journal IF was partialed out; ρ=0.243 (P=0.006) and ρ=0.256 (P=0.004), and after journal 5-year IF was partialed out; ρ=0.235 (P=0.008) and ρ=0.243 (P=0.006) respectively.

Conclusion

There is a positive correlation between the quality and the completeness of a reported SR or MA with citation rate which persists when adjusted for journal IF and journal 5-year IF.     

Importance of Central Retinal Sensitivity for Prediction of Visual Acuity after Intravitreal Bevacizumb in Eyes with Macular Edema Associated with Branch Retinal Vein Occlusion

Objective

To determine whether the baseline retinal sensitivity can predict the best-corrected visual acuity (BCVA) at 1 month after intravitreal bevacizumab (IVB) in eyes with macular edema (ME) associated with a branch retinal vein occlusion (BRVO).

Subjects and Methods

We evaluated 16 eyes of 16 patients who had ME associated with a BRVO. The mean ± standard deviation age was 69.1 ± 8.9 years, and all had a single IVB injection. The BCVA, central macular thickness (CMT), integrity of the ellipsoid zone (EZ) of the photoreceptors, and retinal sensitivity were determined before (baseline) and at 1 day, 1 week, and 1 month following the IVB. The average threshold retinal sensitivity (AT) within the central 10° was determined by Macular Integrity Assessment. The correlations between the BCVA at 1 month and the CMT, integrity of the EZ, and AT at each visit were determined.

Results

One month after IVB, the BCVA improved significantly from 0.56 ± 0.27 logMAR units to 0.32 ± 0.28 logMAR units, and the CMT from 611.4 ± 209.3 μm to 258.7 ± 64.0 μm (P <0.05). The AT improved significantly from 17.9 ± 5.3 dB to 21.2 ± 5.0 dB (P <0.05). At 1 day after the treatment, both the integrity of the EZ (r = 0.59) and the retinal sensitivity (r = 0.76) were moderately correlated with the BCVA at 1 month.

Conclusion

These results indicate that both the integrity of the EZ and the AT at 1 day after the IVB can predict the BCVA after treatment for ME associated with BRVO. There is a possibility that these parameters will predict the effectiveness of IVB for each case.     

Outcomes and Risk Factors for Mortality among Patients Treated with Carbapenems for Klebsiella spp. Bacteremia

Background

Extensive dissemination of carbapenemase-producing Enterobacteriaceae has led to increased resistance among Klebsiella species. Carbapenems are used as a last resort against resistant pathogens, but carbapenemase production can lead to therapy failure. Identification of risk factors for mortality and assessment of current susceptibility breakpoints are valuable for improving patient outcomes.

Aim

The objective of this study was to evaluate outcomes and risk factors for mortality among patients treated with carbapenems for Klebsiella spp. bacteremia.

Methods

Patients hospitalized between 2006 and 2012 with blood cultures positive for Klebsiella spp. who received ≥ 48 hours of carbapenem treatment within 72 hours of positive culture were included in this retrospective study. Patient data were retrieved from electronic medical records. Multivariate logistic regression was used to identify risk factors for 30-day hospital mortality.

Results

One hundred seven patients were included. The mean patient age was 61.5 years and the median APACHE II score was 13 ± 6.2. Overall, 30-day hospital mortality was 9.3%. After adjusting for confounding variables, 30-day mortality was associated with baseline APACHE II score (OR, 1.17; 95% CI, 1.01–1.35; P = 0.03), length of stay prior to index culture (OR, 1.03; 95% CI, 1.00–1.06; P = 0.04), and carbapenem non-susceptible (imipenem or meropenem MIC > 1 mg/L) infection (OR, 9.08; 95% CI, 1.17–70.51; P = 0.04).

Conclusions

Baseline severity of illness and length of stay prior to culture were associated with 30-day mortality and should be considered when treating patients with Klebsiella bacteremia. These data support the change in carbapenem breakpoints for Klebsiella species.     

Serum Levels of the Cancer-Testis Antigen POTEE and Its Clinical Significance in Non-Small-Cell Lung Cancer

Background

POTEE (POTE ankyrin domain family, member E) is a newly identified cancer-testis antigen that has been found to be expressed in a wide variety of human cancers including cancers of the colon, prostate, lung, breast, ovary, and pancreas.

Aim

To measure the serum levels of POTEE in patients with non-small-cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in NSCLC.

Patients and Methods

104 NSCLC patients, 66 benign lung disease patients and 80 healthy volunteers were enrolled in this study from May 2013 to February 2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t tests. Categorical variables were calculated as rates and were analyzed using a χ² test or Fisher’s exact test. Survival curves were estimated and compared using the Kaplan-Meier method and log-rank tests.

Results

Serum POTEE levels were significantly higher in NSCLC patients than in benign lung disease patients and healthy controls (mean ± SD [pg/ml], 324.38± 13.84 vs. 156.93 ± 17.38 and 139.09 ± 15.80, P<0.001) and were significantly correlated with TNM stage. Survival analysis revealed that patients with low serum POTEE had longer progression-free survival (PFS) than those with high serum POTEE (P=0.021). Cox multivariate analysis indicated that POTEE was an independent prognostic factor of progression-free survival (P =0.009, hazard ratio, 2.440).

Conclusions

Serum POTEE level in NSCLC patients is associated with TNM stage and is a potential prognostic factor.     

Pre-Transplant Plasma Torque Teno Virus Load and Increase Dynamics after Lung Transplantation

Background

The human Torque Teno virus (TTV) causes persistent viremia in most immunocompetent individuals. Elevated TTV levels are observed after solid organ transplantation and are related to the extent of immunosuppression especially during the phase of maintenance immunosuppression. However, the extent to which the TTV increase in the early phase post-transplantation is associated with the patient’s immunosuppressive state is unclear.

Objectives

In this study, we assessed the TTV increase dynamics in detail during the first three months after lung transplantation under a defined immunosuppressive regimen and in relation to the pre-transplant TTV level.

Study Design

Forty-six lung transplant recipients (LTRs) were included in this prospective longitudinal study. All received alemtuzumab induction combined with tacrolimus and corticosteroids immunosuppressive therapy. Plasma TTV DNA was monitored before transplantation and regularly within the first three months post-transplantation (n = 320 samples; mean sampling interval: 12.2 days).

Results

In 43/46 LTRs (93%), TTV DNA was detectable before transplantation (median 4.4 log₁₀ copies/mL; range: 2.0–6.4). All 46 LTRs showed a TTV increase post-transplantation, which followed a sigmoidal-shaped curve before the median peak level of 9.4 log₁₀ copies/mL (range: 7.6–10.7) was reached at a median of day 67 (range: 41–92). The individual TTV DNA doubling times (range: 1.4–20.1 days) significantly correlated with the pre-transplant TTV levels calculated over 30 or 60 days post-transplantation (r = 0.61, 0.54, respectively; both P < 0.001), but did not correlate with the mean tacrolimus blood levels. Pre-transplant TTV levels were not associated with time and level of the patients’ post-transplant TTV peak load.

Conclusion

The TTV level may be used to mirror the state of immunosuppression only after the patients’ initial peak TTV level is reached.     

Vascular Cellular Adhesion Molecule-1 (VCAM-1) Expression in Mice Retinal Vessels Is Affected by Both Hyperglycemia and Hyperlipidemia

Background

Inflammation has been proposed to be important in the pathogenesis of diabetic retinopathy. An early feature of inflammation is the release of cytokines leading to increased expression of endothelial activation markers such as vascular cellular adhesion molecule-1 (VCAM-1). Here we investigated the impact of diabetes and dyslipidemia on VCAM-1 expression in mouse retinal vessels, as well as the potential role of tumor necrosis factor-α (TNFα).

Methodology/Principal Findings

Expression of VCAM-1 was examined by confocal immunofluorescence microscopy in vessels of wild type (wt), hyperlipidemic (ApoE^−/−) and TNFα deficient (TNFα^−/−, ApoE^−/−/TNFα^−/−) mice. Eight weeks of streptozotocin-induced diabetes resulted in increased VCAM-1 in wt mice, predominantly in small vessels (<10 µm). Diabetic wt mice had higher total retinal TNFα, IL-6 and IL-1β mRNA than controls; as well as higher soluble VCAM-1 (sVCAM-1) in plasma. Lack of TNFα increased higher basal VCAM-1 protein and sVCAM-1, but failed to up-regulate IL-6 and IL-1β mRNA and VCAM-1 protein in response to diabetes. Basal VCAM-1 expression was higher in ApoE^−/− than in wt mice and both VCAM-1 mRNA and protein levels were further increased by high fat diet. These changes correlated to plasma cholesterol, LDL- and HDL-cholesterol, but not to triglycerides levels. Diabetes, despite further increasing plasma cholesterol in ApoE^−/− mice, had no effects on VCAM-1 protein expression or on sVCAM-1. However, it increased ICAM-1 mRNA expression in retinal vessels, which correlated to plasma triglycerides.

Conclusions/Significance

Hyperglycemia triggers an inflammatory response in the retina of normolipidemic mice and up-regulation of VCAM-1 in retinal vessels. Hypercholesterolemia effectively promotes VCAM-1 expression without evident stimulation of inflammation. Diabetes-induced endothelial activation in ApoE^−/− mice seems driven by elevated plasma triglycerides but not by cholesterol. Results also suggest a complex role for TNFα in the regulation of VCAM-1 expression, being protective under basal conditions but pro-inflammatory in response to diabetes.     

Clinical Significance of the Edema Index in Incident Peritoneal Dialysis Patients

Background

Proper monitoring for volume overload is important to improve prognosis in peritoneal dialysis (PD) patients. The association between volume status and residual renal function (RRF) remains an unresolved issue. The aim of the present study was to evaluate the association between the edema index and survival or RRF in incident PD patients.

Patients and Methods

We identified all adults who underwent PD. The edema index was defined as the ratio of extracellular fluid to total body fluid. Participants with available data regarding survivorship or non-survivorship during the first year after PD initiation were included in the area under the receiver operating characteristic curve analysis. The cutoff value of the edema index for 1-year mortality was >0.371 in men and >0.372 in women. Participants were divided into two groups according to the cutoff value of their baseline edema indices: High (>cutoff value) and Low (≤cutoff value). Survivors during the first year after PD initiation were divided into two groups according to the initial and 1-year edema index: Non-improvement (maintenance of criteria in the initial Low group during the year) and Other (all participants except those in the Non-improvement group).

Results

In total, 631 patients were enrolled in the present study. The cutoff value of the edema index for 1-year mortality was >0.371 in men and >0.372 in women. The respective mean initial RRF values (mL·min^-1·1.73 m^-2) in the Low and High groups, respectively, were 4.88 ± 4.09 and 4.21 ± 3.28 in men (P = 0.108), and 3.19 ± 2.57 and 2.98 ± 2.70 in women (P = 0.531). There were no significant differences between groups in either sex. The respective mean RRF values at 1 year after PD initiation in the Low and High groups, respectively, were 3.56 ± 4.35 and 2.73 ± 2.53 in men, and 2.80 ± 2.36 and 1.85 ± 1.51 in women. RRF at 1 year after PD initiation was higher in the Low group than in the High group (men: P = 0.027; women: P = 0.001). In men, the cumulative 5-year survival rates were 78.7% and 46.2% in the Low and High groups, respectively, whereas in women, rates were 77.2% and 58.8% in the Low and High groups, respectively. For survivors during the first year after PD initiation, the Non-improvement group was associated with a poor survival rate compared with the Other group for both sexes.

Conclusion

A high edema index was associated with mortality in incident PD patients at baseline and follow-up. The edema index may be used as a new marker for predicting mortality in PD patients.     

Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma

Background

Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear.

Methods

The effect of IFN-α treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-α before implantation of tumor was done to explore the effect of IFN-α on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry.

Results

IFN-α treatment did not decrease the number of CTCs (0.075%±0.020% versus 0.063%±0.018%, P = 0.574, IFN-α–treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75±1.0 versus 28.0±6.3, P = 0.008; size [pixels]: 116.8±72.2 versus 5226.4±1355.7, P = 0.020), and inhibited macrophage infiltration (0.20%±0.04% versus 1.36%±0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1±1.7 versus 21.9±0.4, P<0.000) in the lung, which was independent of the primary tumor.

Conclusion

IFN-α inhibited lung metastasis by directly modulating the lung microenvironment.     

Precedent Fluctuation of Serum hs-CRP to Albumin Ratios and Mortality Risk of Clinically Stable Hemodialysis Patients

Background

A high sensitivity C-reactive protein to albumin ratio (hs-CRP/Alb) predicts mortality risk in patients with acute kidney injury. However, it varies dynamically. This study was conducted to evaluate whether a variation of this marker was associated with long-term outcome in clinically stable hemodialysis (HD) patients.

Methods

hs-CRP/Alb was checked bimonthly in 284 clinically stable HD outpatients throughout all of 2008. Based on the “slope” of trend equation derived from 5–6 hs-CRP/alb ratios for each patient, the total number of patients was divided into quartiles—Group 1: β≦ −0.13, n = 71; group 2: β>-0.13≦0.003; n = 71, group 3: β>0.003≦0.20; and group 4: β>0.20, n = 71. The observation period was from January 1, 2009 to August 31, 2012.

Results

Group 1+4 showed a worse long-term survival (p = 0.04) and a longer 5-year hospitalization stay than Group 2+3 (38.7±44.4 vs. 16.7±22.4 days, p<0.001). Group 1+4 were associated with older age (OR = 1.03, 95% CI = 1.01–1.05) and a high prevalence of congestive heart failure (OR = 2.02, 95% CI = 1.00–4.11). Standard deviation (SD) of hs-CRP/Alb was associated with male sex (β = 0.17, p = 0.003), higher Davies co-morbidity score (β = 0.16, p = 0.03), and baseline hs-CRP (β = 0.39, p<0.001). Patients with lower baseline and stable trend of hs-CRP/Alb had a better prognosis. By multivariate Cox proportional methods, SD of hs-CRP/alb (HR: 1.05, 95% CI: 1.01–1.08) rather than baseline hs-CRP/Alb was an independent predictive factor for long-term mortality after adjusting for sex and HD vintage.

Conclusion

Clinically stable HD patients with a fluctuating variation of hs-CRP/Alb are characterized by old age, and more co-morbidity, and they tend to have longer subsequent hospitalization stay and higher mortality risk.