Expression of IGF-IEc Isoform in Renal Cell Carcinoma Tissues.

BACKGROUND/AIM: Insulin-like growth factor-I (IGF-I) regulates various aspects of cancer biology. There is a growing body of evidence regarding the potential distinct role of IGF-I isoforms, particularly of IGF-IEc, in the pathophysiology of various human cancer types, however, there are no studies which examined the expression of the different IGF-I isoforms in renal cell carcinoma (RCC). This study aimed to characterize the expression of IGF-IEc in human RCC tissues and investigated whether its expression is associated with the histopathological type of RCC as well as with the overall survival of patients. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded renal tissue samples from 94 patients (58 males and 36 females) were assessed for IGF-IEc expression by immunohistochemistry. RESULTS: RCC tissues showed mainly cytoplasmic IGF-IEc staining but immunoreactivity of IGF-IEc was also localized in the cell membrane. Significantly lower IGF-IEc expression was found in clear cell RCC vs. all other histological types (p=0.010), and this remained significant after adjusting for tumor size, grade, stage, and mitotic index (p<0.05). No association was found between IGF-IEc expression level and overall survival of patients with RCC. CONCLUSION: The differential expression of IGF-IEc isoform among the RCC histopathological types may indicate its histological type-specific regulation and possibly suggests a discrete biological role of this isoform in the pathophysiology of RCC.

Quantitative INTERSPECIMEN variability during biphasic pleural fluid cytological sampling in adenocarcinoma effusions.

OBJECTIVES: Given that cytology of adenocarcinoma-induced pleural effusions has a high diagnostic yield, we have comparatively evaluated the cytological information of smears during biphasic sampling of pleural fluid in patients with metastatic pleural adenocarcinoma from various primary sites. METHODS: We studied 25 male and 21 female patients, aged 59.4 ±17.2 years (mean ± SD) with unilateral malignant effusion of varying magnitude due to confirmed adenocarcinoma from various primary sites. At thoracocentesis we collected two 30-ml samples of pleural fluid, the first at the very beginning of fluid aspiration (S1) and the second just before termination of fluid removal (S2) and recorded the volume of fluid aspirated between the 2 samples. Cytological smears were examined under light microscopy by 3 independent cytologists after Papanicolaou stain. Quantitative assessment of cell types was averaged among 50 visual fields for each smear. RESULTS: In S1 versus S2 the mean number of mesothelial cells was 7.8 ± 4.8 versus 12.1 ± 5.4 (mean ± SD), of lymphocytes 64.6 ± 12.9 versus 85.9 ± 17.4, of neutrophils 8.5 ± 4.4 versus 11.7 ± 5.2, of eosinophils 1.5 ± 0.3 versus 1.7 ± 0.8, and the number of malignant cell aggregates(NMCA) was 11.9 ±4.9 versus 20.7 ± 5.1. The differences in numbers of all cell types including NMCA were statistically significant between S1 and S2 (P < .01). A strong significant linear association between S2/S1 ratio of NMCA and the volume of fluid aspirated between samples was also found (95% confidence interval [CI], 0.209-0.236, P-value < .001). CONCLUSION: Specimens aspirated before completion of fluid drainage are shown to contain significantly more diagnostic information than those aspirated at the beginning of fluid removal.

Platelet to lymphocyte ratio in acute aortic dissection.

BACKGROUND: Inflammation plays an important role in the initiation and progression of acute aortic dissection (AAD). New inflammatory indices derived from full cell blood count and its differential may be associated with increased risk. We evaluated platelet-lymphocyte (PLR), red cell distribution width (RDW) and RDW/PLT's (platelets) (RPR) in AAD. METHODS: We studied 120 consecutive patients with AAD type I admitted for emergency surgery (group I), 121 consecutive patients with aortic aneurysms of the ascending aorta prior to elective repair (group II) and 121 controls (group III), age and sex matched. RESULTS: PLR was significantly higher in group I vs both groups II and III (P < .001). There was an excellent correlation of PLR with neutrophil/lymphocyte ratio (NLR) in all three groups (P < .001 for all). After adjustment for hemoglobin, RDW did not differ but RPR remained significantly higher in group I compared to groups II and III (P < .001). The best cutoff value of PLR to predict dissection was 159 with 53% sensitivity and 86% specificity. No association between PLR, RDW, and RPR and mortality in group I was found. CONCLUSIONS: Indices derived from full cell blood count may provide diagnostic information in patients with AAD; whether these indices may contribute to prognosis assessment should be further investigated.

High levels of IL-6 and IL-8 characterize early-on idiopathic pulmonary fibrosis acute exacerbations.

INTRODUCTION: Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients. METHODS: Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well asactive transforming growth factor-beta (TGF-ß) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied. RESULTS: Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p=0.002 and p=0.046, respectively). An increase in either IL-6 or IL-8 by 1pg/ml increases the odds of death by 5.6% (p=0.021) and 6.7% (p=0.013), respectively, in all patients. No differences were detected for the other cytokines. CONCLUSION: High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-ß, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.

Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery.

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5 ± 10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7 ± 9.2% and low logistic EuroScore (3.5 ± 3.2%) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11-24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p = 0.007]. OPN levels were positively related to EuroScore (r = 0.2, p = 0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p = 0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43-4.99), p = 0.527]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p = 0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome.

Management and postoperative outcome in primary lung cancer and heart disease co-morbidity: a systematic review and meta-analysis.

BACKGROUND: Co-morbidity of primary lung cancer (LC) and heart disease (HD), both requiring surgical therapy, characterizes a high risk group of patients necessitating prompt diagnosis and treatment. The aim of this study is the review of available evidence guiding the management of these patients. METHODS: Postoperative outcome of patients operated for primary LC (first meta-analysis) and for both primary LC and HD co-morbidity (second meta-analysis), were studied. Parameters examined in both meta-analyses were thirty-day postoperative mortality, postoperative complications, three- and five-year survival probabilities. The last 36 years were reviewed by using the PubMed data base. Thirty-seven studies were qualified for both meta-analyses. RESULTS: The pooled 30-day mortality percentages (%) were 4.16% [95% confidence interval (CI): 2.68-5.95] (first meta-analysis) and 5.26% (95% CI: 3.47-7.62) (second meta-analysis). Higher percentages of squamous histology and lobectomy, were significantly associated with increased (P=0.001) and decreased (P<0.001) thirty-day postoperative mortality, respectively (first meta-analysis). The pooled percentages for postoperative complications were 34.32% (95% CI: 24.59-44.75) (first meta-analysis) and 45.59% (95% CI: 35.62-55.74) (second meta-analysis). Higher percentages of squamous histology (P=0.001), lobectomy (P=0.002) and p-T1 or p-T2 (P=0.034) were associated with higher proportions of postoperative complications (second meta-analysis). The pooled three- and five- year survival probabilities were 68.25% (95% CI: 45.93-86.86) and 52.03% (95% CI: 34.71-69.11), respectively. Higher mean age (P=0.046) and percentage lobectomy (P=0.009) significantly reduced the five-year survival probability. CONCLUSIONS: Lobectomy and age were both accompanied by reduced five-year survival rate. Also, combined aorto-coronary bypass grafting (CABG) with lobectomy for squamous pT1 or pT2 LC displayed a higher risk of postoperative complications. Moreover, medical decision between combined or staged surgery is suggested to be individualized based on adequacy of coronary arterial perfusion, age, patient's preoperative performance status (taking into account possible co-morbidities per patient), tumor's staging and extent of lung resection.

Short-term associations between particle oxidative potential and daily mortality and hospital admissions in London.

BACKGROUND: Particulate matter (PM) from traffic and other sources has been associated with adverse health effects. One unifying theory is that PM, whatever its source, acts on the human body via its capacity to cause damaging oxidation reactions related to its content of pro-oxidants components. Few epidemiological studies have investigated particle oxidative potential (OP) and health. We conducted a time series analysis to assess associations between daily particle OP measures and numbers of deaths and hospital admissions for cardiovascular and respiratory diseases. METHODS: During 2011 and 2012 particles with an aerodynamic diameter less than 2.5 and 10µm (PM2.5 and PM10 respectively) were collected daily on Partisol filters located at an urban background monitoring station in Central London. Particulate OP was assessed based on the capacity of the particles to oxidize ascorbate (OP(AA)) and glutathione (OP(GSH)) from a simple chemical model reflecting the antioxidant composition of human respiratory tract lining fluid. Particulate OP, expressed as % loss of antioxidant per µg of PM, was then multiplied by the daily concentrations of PM to derive the daily OP of PM mass concentrations (% loss per m(3)). Daily numbers of deaths and age- and cause-specific hospital admissions in London were obtained from national registries. Poisson regression accounting for seasonality and meteorology was used to estimate the percentage change in risk of death or admission associated with an interquartile increment in particle OP. RESULTS: We found little evidence for adverse associations between OP(AA) and OP(GSH) and mortality. Associations with cardiovascular admissions were generally positive in younger adults and negative in older adults with confidence intervals including 0%. For respiratory admissions there was a trend, from positive to negative associations, with increasing age although confidence intervals generally included 0%. CONCLUSIONS: Our study, the first to analyse daily particle OP measures and mortality and admissions in a large population over two years, found little evidence to support the hypothesis that short-term exposure to particle OP is associated with adverse health effects. Further studies with improved exposure assessment and longer time series are required to confirm or reject the role of particle OP in triggering exacerbations of disease.

Associations of short-term exposure to traffic-related air pollution with cardiovascular and respiratory hospital admissions in London, UK.

OBJECTIVES: There is evidence of adverse associations between short-term exposure to traffic-related pollution and health, but little is known about the relative contribution of the various sources and particulate constituents. METHODS: For each day for 2011-2012 in London, UK over 100 air pollutant metrics were assembled using monitors, modelling and chemical analyses. We selected a priori metrics indicative of traffic sources: general traffic, petrol exhaust, diesel exhaust and non-exhaust (mineral dust, brake and tyre wear). Using Poisson regression models, controlling for time-varying confounders, we derived effect estimates for cardiovascular and respiratory hospital admissions at prespecified lags and evaluated the sensitivity of estimates to multipollutant modelling and effect modification by season. RESULTS: For single day exposure, we found consistent associations between adult (15-64 years) cardiovascular and paediatric (0-14 years) respiratory admissions with elemental and black carbon (EC/BC), ranging from 0.56% to 1.65% increase per IQR change, and to a lesser degree with carbon monoxide (CO) and aluminium (Al). The average of past 7 days EC/BC exposure was associated with elderly (65+ years) cardiovascular admissions. Indicated associations were higher during the warm period of the year. Although effect estimates were sensitive to the adjustment for other pollutants they remained consistent in direction, indicating independence of associations from different sources, especially between diesel and petrol engines, as well as mineral dust. CONCLUSIONS: Our results suggest that exhaust related pollutants are associated with increased numbers of adult cardiovascular and paediatric respiratory hospitalisations. More extensive monitoring in urban centres is required to further elucidate the associations.

Short-term exposure to traffic-related air pollution and daily mortality in London, UK.

Epidemiological studies have linked daily concentrations of urban air pollution to mortality, but few have investigated specific traffic sources that can inform abatement policies. We assembled a database of >100 daily, measured and modelled pollutant concentrations characterizing air pollution in London between 2011 and 2012. Based on the analyses of temporal patterns and correlations between the metrics, knowledge of local emission sources and reference to the existing literature, we selected, a priori, markers of traffic pollution: oxides of nitrogen (general traffic); elemental and black carbon (EC/BC) (diesel exhaust); carbon monoxide (petrol exhaust); copper (tyre), zinc (brake) and aluminium (mineral dust). Poisson regression accounting for seasonality and meteorology was used to estimate the percentage change in risk of death associated with an interquartile increment of each pollutant. Associations were generally small with confidence intervals that spanned 0% and tended to be negative for cardiovascular mortality and positive for respiratory mortality. The strongest positive associations were for EC and BC adjusted for particle mass and respiratory mortality, 2.66% (95% confidence interval: 0.11, 5.28) and 2.72% (0.09, 5.42) per 0.8 and 1.0 µg/m(3), respectively. These associations were robust to adjustment for other traffic metrics and regional pollutants, suggesting a degree of specificity with respiratory mortality and diesel exhaust containing EC/BC.

Comparative changes in tissue oxygenation between laparoscopic and open cholecystectomy.

BACKGROUND: Previous studies examined the effect of laparoscopic cholecystectomy (LC) versus open cholecystectomy (OC) on physiological variables of the respiratory system. In this study we compared changes in arterial blood gases-related parameters between LC and OC to assess their comparative influence on gas exchange. METHODS: We studied 28 patients, operated under identical anesthetic protocol (LC: 18 patients, OC: 10 patients). Measurements were made on the morning before surgery (BS), the second (AS2) and the eighth (AS8) postoperative day. Studied parameters, including alveolar-arterial difference in PO2 ((A-a)DO2) and oxygen content (Oct in vol%), were statistically compared. RESULTS: On AS2 a greater increase was found in ((A-a)DO2) for the OC compared to LC (4.673 ± 0.966 kPa versus 3.773 ± 1.357 kPa, respectively). Between BS and AS2, Oct in vol% decreased from 17.55 ± 1.90 to 15.69 ± 1.88 in the LC and from 16.99 ± 2.37 to 14.62 ± 2.23 in the OC, whilst a reduction (P = 0.093) between AS2 and AS8 was also found for the open method. Besides, on AS2, SaO2% decrease was greater in OC compared to LC (P = 0.096). CONCLUSIONS: On AS2, the greater increase in OC-((A-a)DO2) associated with Oct in vol% and SaO2% findings also in OC group suggest that LC might be associated with lower risk for impaired tissue oxygenation.

Vascular endothelial growth factor inhibitors for treatment of corneal neovascularization: a meta-analysis.

PURPOSE: To evaluate the therapeutic effect of bevacizumab (Avastin) on corneal neovascularization (NV). METHODS: Systematic review and meta-analysis of the literature was performed. Seven eligible clinical human studies and 18 eligible experimental animal studies examining the effectiveness of bevacizumab treatment on corneal NV were included in the meta-analysis. Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened, and data were extracted from each eligible study. The random-effects model (of DerSimonian and Laird) was used to combine the results from the selected studies. Heterogeneity was explored using available data. Publication bias was also assessed. RESULTS: A significant reduction of corneal neovascularized area was seen in clinical human studies, with a pooled reduction of 36% [95% confidence interval (CI), 18%-54%] overall, of 32% (95% CI, 10%-54%) for subconjunctival anti-vascular endothelial growth factor injections, and 48% (95% CI, 32%-65%) for topical treatment. Pooled mean change in best-corrected visual acuity showed an improvement in best-corrected visual acuity by 0.04. The summary standardized mean difference in animal studies indicated a statistically significant reduction in the area of corneal NV when treated with bevacizumab compared with the control group by -1.71 (95% CI, -2.12 to -1.30). The subtotal pooled standardized mean differences were -1.83 (95% CI, -2.38 to -1.28) for subconjunctival anti-vascular endothelial growth factor injections and -1.50 (95% CI, -1.88 to -1.12) for topical treatment. CONCLUSION: Our results suggest that both topical and subconjunctival bevacizumab achieve significant reduction in the area of corneal NV. This meta-analysis provides an evidential basis for the new therapeutic concept of treating corneal NV with antiangiogenic therapy.

High homocysteine and low folate concentrations in acute aortic dissection.

BACKGROUND: Biomarkers for monitoring progression and prognosis of thoracic aneurysm are of great interest. Homocysteine (Hcy) induces elastolysis in arterial media and may directly affect fibrillin-1 or collagen whereas lipoprotein (Lp) (a) inhibits elastolysis by reducing activation of matrix metallopeptidase-9. METHODS: We studied 31 consecutive patients with acute aortic dissection (AAD) admitted for emergency surgery (group I, 60 ± 13 years old, 25 men), 30 consecutive patients with chronic aneurysms of the ascending aorta (group II, 67 ± 12 years old, 24 men) and 20 healthy controls (group III, 58 ± 15 years old, 14 men). We evaluated Hcy, folate, B12, Lp(a) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism at baseline. RESULTS: Hcy, folate and B12 differed significantly among the 3 studied groups (P=0.016, P=0.004 and P=0.001, respectively). The levels of Hcy and B12 were significantly higher in group I compared to both groups II and III (P=0.05 and P=0.002, P<0.001 and P=0.017, respectively) and without significant differences between groups II and III (P=0.083 and P=0.124). Folate was significantly lower in group I compared to both groups II and III (P=0.001 and P=0.006, respectively) and without marked difference between groups II and III (P=0.409). No significant difference was found in serum levels of Lp (a) (P=0.074) or among the frequency of MTHFR C677T genotypes. CONCLUSIONS: Patients with AAD present with higher Hcy and lower folate compared to both chronic aneurysms and controls.