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The report “Effects of Air Temperature Modified by Vulnerability Factors” was prepared as a milestone by researchers in the EU Project EXHAUSTION*. This report summarises the evidence on the interactive effects of high air temperature and various vulnerability factors, including the environmental, socio-economic, and individual behavioral factors on heart- and lung-related deaths and diseases (cardiopulmonary mortality and morbidity) across Europe. The study was conducted at the city, small-area (e.g., municipalities), and individual level. The findings show a greater vulnerability to heat for people living in urban areas with dense population, high air pollution levels, low coverage of green spaces, as well as areas with low Gross Domestic Product. Moreover, people with chronic pre-existing diseases and the elderly were found to be at greater risk. The findings highlight the urgent need to improve the urban environment as well as the health status and living conditions in European cities to contrast the impacts of heat and future climate change. This report alerts stakeholders and policymakers that targeted climate change adaptation measures need to be considered to protect vulnerable population and thereby increase European resilience to climate change.

Land use regression (LUR) and dispersion/chemical transport models (D/CTMs) are frequently applied to predict exposure to air pollution concentrations at a fine scale for use in epidemiological studies. Moreover, the use of satellite aerosol optical depth data has been a key predictor especially for particulate matter pollution and when studying large populations. Within the STEAM project we present a hybrid spatio-temporal modeling framework by (a) incorporating predictions from dispersion modeling of nitrogen dioxide (NO2), ozone (O3) and particulate matter with an aerodynamic diameter equal or less than 10 μm (PM10) and less than 2.5 μm (PM2.5) into a spatio-temporal LUR model; and (b) combining the predictions LUR and dispersion modeling and additionally, only for PM2.5, from an ensemble machine learning approach using a generalized additive model (GAM). We used air pollution measurements from 2009 to 2013 from 62 fixed monitoring sites for O3, 115 for particles and up to 130 for NO2, obtained from the dense network in the Greater London Area, UK. We assessed all models following a 10-fold cross validation (10-fold CV) procedure. The hybrid models performed better compared to separate LUR models. Incorporation of the dispersion estimates in the LUR models as a predictor, improved the LUR model fit: CV-R2 increased to 0.76 from 0.71 for NO2, to 0.79 from 0.57 for PM10, to 0.81 to 0.66 for PM2.5 and to 0.75 from 0.62 for O3. The CV-R2 obtained from the hybrid GAM framework was also increased compared to separate LUR models (CV-R2 = 0.80 for NO2, 0.76 for PM10, 0.79 for PM2.5 and 0.75 for O3). Our study supports the combined use of different air pollution exposure assessment methods in a single modeling framework to improve the accuracy of spatio-temporal predictions for subsequent use in epidemiological studies.

Identifying how greenspace impacts the temperature-mortality relationship in urban environments is crucial, especially given climate change and rapid urbanization. However, the effect modification of greenspace on heat-related mortality has been typically focused on a localized area or single country. This study examined the heat-mortality relationship among different greenspace levels in a global setting., This publication was developed under Assistance Agreement No. RD83587101 awarded by the U.S. Environmental Protection Agency to Yale University. It has not been formally reviewed by EPA. The views expressed in this document are solely those of the authors and do not necessarily reflect those of the Agency. EPA does not endorse any products or commercial services mentioned in this publication. Research reported in this publication was also supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD012769. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Also, this work has been supported by the National Research Foundation of Korea (2021R1A6A3A03038675), Medical Research CouncilUK (MR/V034162/1 and MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/ R009384/1), Academy of Finland (Grant ID: 310372), European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655 and 874990), Czech Science Foundation (22-24920S), Emory University’s NIEHS-funded HERCULES Center (Grant ID: P30ES019776), and Grant CEX2018-000794-S funded by MCIN/AEI/ 10.13039/501100011033 The funders had no role in the design, data collection, analysis, interpretation of results, manuscript writing, or decision to publication.

The report “Effects of air Temperature on Cardiopulmonary Mortality and Morbidity in Europe” was prepared as a milestone of the EU Project EXHAUSTION. It summarizes the evidence on the effects of different levels and changes in ambient air temperature on cardiopulmonary (CPD) mortality and morbidity across Europe and puts a spotlight on the vulnerable and susceptible population. It can help stakeholders and policymakers to plan adaptation measures to protect the vulnerable and susceptible population and increase European resilience towards climate change and extreme weather events.

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

Although the health effects of short-term exposure to ambient particles have been well documented, there is a need to update scientific knowledge due to the continuously changing profile of the air pollution mixture. Furthermore the effect of the severe economic crisis in Greece that started in 2008 on previously reported associations has not been studied. We assessed the change in mortality risk associated with short-term exposure to PM10 in Athens, Greece during 2001–12.Time-series data on the daily concentrations of regulated particles and all cause, cardiovascular and respiratory mortality were analyzed using overdispersed Poisson regression models, controlling for time-varying confounders such as seasonality, meteorology, influenza outbreaks, summer holidays and day of the week. We assessed changes in risk over time by inclusion of an interaction term between particles' levels and time or predefined periods, i.e. 2001–07 and 2008–12.While the related mortality risks increased over the analyzed period, the difference before and after 2008 was significant only for total mortality (p-value for interaction .03) and driven by the difference observed among those ≥75 years. An interquartile increase in PM10 before 2008 was associated with 1.51% increase in deaths among ≥75 years (95% Confidence interval (CI): 0.62%, 2.40%), while after 2008 with a 2.61% increase (95%CI: 1.72%, 3.51%) (p-value for interaction .01).Our results indicate that despite the decline in particles' concentration in Athens, Greece during 2001–12 the associated mortality risk has possibly increased, suggesting that the economic crisis initiated in 2008 may have led to changes in the particles' composition due to the ageing of the vehicular fleet and the increase in the use of biomass fuel for heating. Keywords: Air pollution, Mortality risk, Particulate matter, Short-term effects, Trends

Abstract The health effects of acute exposure to temperature extremes are established; those of long-term exposure only recently received attention. We performed a systematic review to assess the associations of long-term (>3 months) exposure to higher or lower temperature on total and cardiopulmonary mortality and morbidity, screening 3455 studies and selecting 34. The studies were classified in those observing associations within a population over years with changing annual temperature indices and those comparing areas with a different climate. We also assessed the risk of bias, adapting appropriately an instrument developed by the World Health Organization for air pollution. Studies reported that annual temperature indices for extremes and variability were associated with annual increases in mortality, indicating that effects of temperature extremes cannot be attributed only to short-term mortality displacement. Studies on cardiovascular mortality indicated stronger associations with cold rather than hot temperature, whilst those on respiratory outcomes reported effects of both heat and cold but were few and used diverse health outcomes. Interactions with air pollution were not generally assessed. The few studies investigating effect modification showed stronger effects among the elderly and those socially deprived. Comparisons of health outcome prevalence between areas reported lower blood pressure and a tendency for higher obesity in populations living in warmer climates. Our review indicated interesting associations between long-term exposure to unusual temperature levels in specific areas and differences in health outcomes and cardiovascular risk factors between geographical locations with different climate, but the number of studies by design and health outcome was small. Risk of bias was identified because of the use of crude exposure assessment and inadequate adjustment for confounding. More and better designed studies, including the investigation of effect modifiers, are needed.

Elevated urban temperatures and heatwaves are a serious threat to the health and wellbeing of the continuously growing urban population and are projected to worsen under climate change. For this reason well-informed disaster risk reduction (DRR) actions, where science and technology play a key role, are required. However insufficient communication between scientific and policy-making communities (known as the science-policy gap) hampers the use of science in DRR. Hence there is a strong need to interpret existing scientific knowledge into actionable knowledge, i.e. science that is useful, usable and used. This article presents a series of services and tools that build-upon existing scientific knowledge and aim to provide actionable knowledge to authorities and citizens for reducing the risks of elevated urban temperatures. The above were implemented in the context of the European Commission’s Thermal Risk rEduction Actions and tools for secURE cities (TREASURE) project, and address many of the goals and priorities for action set in the Sendai framework for disaster risk reduction (SFDRR) of the United Nations. A key policy-making user of the implemented services and tools is the City of Athens in Greece, which is one of the largest metropolitan areas in Europe.

Background Inconsistent and contradictory findings have appeared in the literature concerning the impact of body position on oxygenation in pleural effusion. Methods We attempted to elucidate whether the size of the pleural effusion in patients with no parenchymal disease is the main determinant of posture-induced alterations in oxygenation parameters. We studied 62 spontaneously breathing patients aged 65.3±7.8 years (mean±SD), of whom 36 had large and massive-sized effusions (Group A) and 26 had small and moderate-sized effusions (Group B). Arterial blood gases were determined in four different body positions: sitting (SIT), supine (SUP), ipsilateral (IPS) and contralateral (CON) to the effusion side, after remaining relaxed for at least 20 min in each position. Separation into groups A and B was deliberately set from the position of the fluid meniscus line on a posteroanterior chest film just above the upper costal margin of the sixth anterior rib. A two-way ANOVA model with outcome variables PaO2, PaCO2 and [A–a] DO2 was used. Results In both groups the best oxygenation was found in SIT. The worst oxygenation (highest [A–a] DO2 value) occurred in group A in CON compared with IPS (59.4±7.6 vs 49.0±7.5 mm Hg, p Conclusions Patients with large-sized effusions exhibit the worst oxygenation when lying on the side contralateral to the effusion, while those with small-sized effusions exhibit the worst oxygenation when lying on the side ipsilateral to the effusion.

Background Several studies investigated the effects of thoracocentesis on aspects of respiratory function without generally ensuring absence of coexistent lung pathology or homogeneity in initial size of the effusion. Methods We studied 90 patients aged 61.6±15.9 years (mean±SD) separated into a group A with small-sized or medium-sized effusion (A=56 patients) and a group B with large and massive one (B=34 patients). There was no significant lung lesion or cardiovascular pathology. The basic spirometric parameters and maximal respiratory pressures were recorded on three instances: just before thoracocentesis (T1), 30 min after completion of the procedure (T2) and after 48 hours (T3). Results At T2 vs T1, groups A and B respectively presented significant change (mean±SD) (increase) in forced vital capacity (FVC) of 0.071±0.232 and 0.139±0.224 L, in forced expiratory volume in 1 s (FEV1) of 0.127±0.231 and 0.201±0.192 L, in FEV1/FVC of 2.8% and 4.9%, in peak expiratory flow rate (PEFR) of 0.342±0.482 and 0.383±0.425 L/s, in maximal expiratory pressure (MEP) of 0.049±0.037 and 0.049±0.039 kPa and in maximal inspiratory pressure (MIP) of 0.040±0.041 kPa only in group A while decrease in MIP with significant change of 0.055±0.051 kPa in group B. At T3 vs T2 in groups A and B, there was significant change (decrease) in FEV1/FVC of 2.7% and 4.6% as well as significant change (increase) in MIP of 0.036±0.046 and 0.115±0.060 and in MEP of 0.049±0.043 and 0.070±0.048 kPa. Conclusions Thoracocentesis is associated with progressive-small relative to the volume of fluid removed-increases in lung volumes. In larger effusions at T2, a transient decrease in MIP is observed presumably due to temporary geometric distortion of the diaphragm immediately after fluid removal.

Introduction Acute aortic dissection (AAD) represents surgical emergency and current literature mainly consists of postoperative outcome reports. Long term outcome and quality of life have not extensively been investigated. Purpose This is a single center study to assess long term outcome and quality of life of patients who underwent emergency surgery for AAD. Methods From January 2007 until December 2009, 74 consecutive patients were operated for AAD type A in our hospital. Seventeen died during hospital stay and 12 died during follow-up. Mean follow up was 108±10 months. Seventeen patients refused to answer the SF-36 questionnaire; therefore our study group consists of 28 patients. The SF-36 Questionnaire was retrospectively obtained by phone calls, the first, fifth and tenth postoperative year and 2 summary scores are reported, physical (PCS) and mental (MCS). Results Our in-hospital mortality was 23%, late mortality 21.1% and the overall mortality was 39.2%. Significant differences in both physical and mental score over time were found among the 28 long-term survivors (Table). Both PCS and MCS at 1st, 5th and 10th year did not differ compared to age-matched general population but compared to subjects with one or more chronic diseases both PCS and MCS were both significantly better at 5yrs in our patients vs controls (p=0.0028 and p=0.0259, respectively). Likewise, at 5 years PCS but not MCS was better in comparison to subjects with a history of one hospitalization the preceding year (p=0.035 and p=0.1, respectively). Descriptive statistics of physical and mental component summary score over time Score 1 year (FU1) 5 years (FU2) 10 years (FU3) p-value Mean (SD) Mean (SD) Mean (SD) PCS 45.4 (7.7) 50.3 (7.0) 46.8 (9.2) 0.008* MCS 42.8 (15.1) 49.7 (12.7) 49.1 (12.3) 0.001** PCS, Physical component summary; *1 vs 5: p=0.003, 1 vs 10: p=0.469, 5 vs 10: p=0.027. MCS, Mental component summary; **1 vs 5: p=0.001, 1 vs 10: p=0.001, 5 vs 10: p=0.939. SD, standard deviation. Conclusion Quality of life improves after the 1st post-operative year and is comparable to healthy subjects. Although acute dissection is a catastrophic event with high mortality despite successful and timely repair, long term survival and quality of life on the long term are favorable.

Background It is known that on days with high temperatures higher mortality is observed and there is a minimum mortality temperature (MMT) point which is higher in places with warmer climate. This indicates some population adaptation to local climate but information on how quickly this adaptation will occur under climate change is lacking. Methods To investigate this, we associated daily mortality data with temperature during the warm period in 2004–2013 for London inhabitants born in five climatic zones (UK, Tropical, Sub-tropical, Boreal and Mixed). We fitted Poisson regression with distributed-lag non-linear models for each climatic zone group separately to estimate group-specific exposure-response associations and MMTs. We report relative risks of death comparing the 95th percentile (21 °C) and maximum (25 °C) of the temperature distribution in London with the zone-specific minimum mortality temperature. Results No heat-related mortality was observed for people born in countries with Sub-tropical and Mixed climates. We observed an increase of 26%, 35% and 39% in the risk of death at 25 °C compared to the MMT in people born in the UK (marine climate), Tropical and Boreal climate respectively. The temperatures with the lowest mortality in these groups ranged from 15.9 to 17.7 °C. Discussion Our findings imply that people born in different climatic zones do not adapt fully to their new environment within their lifetime. This implies that populations may not adapt readily to climate change and will suffer increased effects from heat. In the presence of climate change, policy makers should be aware of a delayed process of adaptation.

Background Critical care management of patients undergoing transcatheter aortic valve implantation (TAVI) is a major determinant of their outcome. Aims The aim of this study was to compare the prognostic performance of four general scoring systems [Acute Physiology and Chronic Health Evaluation (APACHE), Simplified Acute Physiology Score (SAPS), Sequential Organ Failure Assessment (SOFA), and MultiOrgan Dysfunction (MOD) scores] in TAVI patients. Methods Between 1 June 2008 and 30 June 2014, 75 patients (81.2 ± 6.4 years old, 36 men and 39 women) who underwent TAVI were scored during the first 24 h of their stay at the intensive care unit (ICU). The outcome measures were in-hospital and 30-day mortality and in-hospital and 30-day morbidity defined as myocardial infarction, implantation of permanent pacemaker, stroke, tamponade, major bleeding, vascular access site complications and prolonged ventilation. Results Four patients (5.3%) died in ICU and one more during follow-up, indicating a 30-day mortality rate of 6.6%. Regarding in-hospital mortality, the area under the ROC curve (AUC) was 0.92 for SAPS II, 0.88 for APACHE II, 0.73 for MODS and 0.74 for SOFA. Regarding 30 day-mortality, SAPS II and APACHE II performed equally higher (AUC = 0.88) than the other two scores (0.79 for MODS and 0.80 for SOFA). SAPS II had the best calibration among all four scores for in-hospital and 30-day mortality ( χ2 = 3.06 and χ2 = 3.29, respectively). AUCs for in-hospital and 30-day morbidity were above 0.7 for SAPS II and APACHE II. Conclusions SAPS II and APACHE II are reliable mortality and morbidity risk stratification models for TAVI patients with high calibration and discrimination.

Background/Aim:The health effects of extreme temperatures are well documented at population level. Within the TREASURE project, a smartphone application developed to provide services to citizens du...

Legislation controlling vehicle emissions has been credited with a general downward trend in NOx (NO2+NO) concentrations in Europe since the 1990's. However, recent studies suggest that traffic (roadside) (TR) NO2 concentrations have not decreased as expected, and in some cases increased, most likely due to the use of oxidation catalysts and particle filters in diesel vehicles (EURO III, IV, V, VI). In this study we describe the time trends in NOx, NO2 and NO concentrations in 9 European cities comparing TR and urban background (UB) monitoring locations. In each city, we collected hourly city-specific NOx, NO, and NO2 data from one TR and one UB monitoring site for each year. We describe hourly, weekly, seasonal and inter-annual patterns for periods corresponding to the implementation dates of various EURO vehicle emission standards regulating NOx emissions. The diurnal patterns in all 9 cities strongly reflected morning and evening traffic. In addition, lower weekend concentrations were observed. The NOx concentrations from the TR sites remain unchanged in the majority of the cities over the study period. When stratified by 3 time periods according to the implementation of the EURO standards, an increasing NO2/NOx ratio in 7/9 cities with time was noted. However, over the same time period the NO/NO2 ratio decreased in 8/9 cities. A permanent inversion of the NO/NO2 ratio was observed to occur in 2003 in 5/9 cities. Our analyses of temporal and diurnal patterns of NOx in European cities show reductions in concentrations consistent with reductions in primary emissions likely arising from the implementation of successive EURO standards. The generally constant or increasing NO2 concentrations in the majority of the cities assessed over the study period underline the need of further regulative measures to meet the air quality standards and consequently to minimise adverse effects on human health. The ongoing collection and analysis of pollution concentrations across the EU is recommended to monitor trends in pollutants associated with adverse health effects.

Epidemiological time series studies suggest daily temperature and humidity are associated with adverse health effects including increased mortality and hospital admissions. However, there is no consensus over which metric or lag best describes the relationships. We investigated which temperature and humidity model specification most adequately predicted mortality in three large European cities. Daily counts of all-cause mortality, minimum, maximum and mean temperature and relative humidity and apparent temperature (a composite measure of ambient and dew point temperature) were assembled for Athens, London, and Rome for 6 years between 1999 and 2005. City-specific Poisson regression models were fitted separately for warm (April-September) and cold (October-March) periods adjusting for seasonality, air pollution, and public holidays. We investigated goodness of model fit for each metric for delayed effects up to 13 days using three model fit criteria: sum of the partial autocorrelation function, AIC, and GCV. No uniformly best index for all cities and seasonal periods was observed. The effects of temperature were uniformly shown to be more prolonged during cold periods and the majority of models suggested separate temperature and humidity variables performed better than apparent temperature in predicting mortality. Our study suggests that the nature of the effects of temperature and humidity on mortality vary between cities for unknown reasons which require further investigation but may relate to city-specific population, socioeconomic, and environmental characteristics. This may have consequences on epidemiological studies and local temperature-related warning systems.

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 PO 2 ((A-a)DO 2 ) and oxygen content (Oct in vol%), were statistically compared. Results: On AS2 a greater increase was found in ((A-a)DO 2 ) 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, SaO 2 % decrease was greater in OC compared to LC (P = 0.096). Conclusions: On AS2, the greater increase in OC-((A-a)DO 2 ) associated with Oct in vol% and SaO 2 % findings also in OC group suggest that LC might be associated with lower risk for impaired tissue oxygenation. J Clin Med Res. 2015;7(4):232-241 doi: http://dx.doi.org/10.14740/jocmr2086w

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

Acute exacerbation of Idiopathic Pulmonary Fibrosis (AE-IPF) represents an acute, clinically significant respiratory deterioration of unidentifiable cause with high mortality. The potential role of air pollution on this devastating event in the progress of IPF has not been yet elucidated. This study aims to determine the association between air pollution exposure and AE-IPF. All consecutive IPF patients referred to our department from October-2013 to October-2016 were studied. Demographic, functional data and AE-IPF events were recorded. Blood levels of IL-6 and IL-8 were measured. Air pollution exposures were assigned to each patient retrospectively, for ozone, nitrogen dioxide and particulate matter, based on geo-coded residential addresses. Logistic regression models and Spearman correlation were used to assess air pollutants’ association with AE-IPF and pro-inflammatory mediators. A total of 94 IPF (43 AE-IPF) patients were included in the analysis. AE-IPF patients presented significantly higher levels of IL-6 and IL-8 compared to stables. A positive, non-significant association, between AE-IPF and a 10 μg/m 3 increase in previous year mean level of NO 2 (OR=1.021, 95% CI 0.825-1.265) and O 3 (OR=1.002, 95% CI 0.769-1.305) as well as short-term exposure to NO 2 (OR Lag0-1 =3.024, 95% CI 0.631-14.498; OR antecedent month =3.586, 95% CI 0.565-22.741; OR antecedent 6weeks =3.554, 95% CI 0.470-26.860) was found. A significant positive association was observed between IL-8 and NO 2 whilst a negative one with O 3 for all patients. There is some indication that short as well as long term exposure to increased concentrations of air pollutants is associated to AE-IPF. Studies with more patients to achieve appropriate statistical power are needed.

Body position has been known to affect ventilation/perfusion homogeneity in patients with unilateral lung disease. In our study we investigated changes in oxygenation at different body positions of patients with unilateral pleural effusions without significant (> 1.5cm maximal diameter) parenchymal lesion We studied 47 patients (32 male & 15 female) aged 66.3±6.7yrs. (mean ±SD) of whom group 1 (26pts.) had small effusion (SE) while group 2 (21 pts.) had a large effusion (LE) the dichotomy between groups being arbitrarily set just above the superior margin of anterior 4th rib on chest X-ray. Arterial blood gases were determined in 4 body positions: sitting (SI), supine (SU), lying on the ipsilateral to effusion side (IP) and on the contralateral side (CO), after remaining at each position for 20 minutes. Changes in alveolar-arterial difference in PO2 (A-a)PO2 were eva luated by ANOVA for related samples. [A-a]PO2 in Group 1 changed from 32.2, 39.5, 41.1 and 33.7 mmHg respectively (p

Background There have been contradicting reports in the literature regarding the impact of pleural fluid aspiration on patients’ oxygenation. The aim of this study was to assess the role of the initial size of effusion on post-drainage oxygenation. Methods We studied 122 patients, aged (mean±SD) 61.2±16.8 years, with unilateral pleural effusion and no remarkable parenchymal lesion, by determining PaO2, PaCO2 and [A−a] PaO2 just before thoracocentesis (T1), 30 min after its completion (T2) and 48 hours after the procedure (T3). Patients were divided into group A (75 patients) with small and moderate sized effusions and group B (47 patients) with large and massive effusions. The position of the meniscus line on the posteroanterior film, being arbitrarily set at just above the upper costal margin of the sixth anterior rib, was used to divide the two groups. Patients were studied at rest, breathing room air in the sitting position. Repeated measures ANOVA (related samples) and the Friedman test when the normality assumption was violated were used. Results In group A, at T3, PaO2(mm Hg) showed a statistically significant increase versus T1 (p Conclusion Patients with smaller effusions showed a small improvement in their oxygenation 48 hours post-thoracocentesis (T3). Patients with larger effusions exhibited a transient reduction in their oxygenation immediately after fluid removal (T2).

Following the implementation of three successive European Directives during the 1990s to reduce the sulphur content of fuels, background SO2 concentrations in European cities have fallen substantially. We investigated the magnitude of the short-term associations between daily SO2 concentrations and mortality during the various phases of legislation. Daily counts of all-cause and cause-specific mortality, SO2 concentration, temperature and humidity were obtained for 20 European cities participating in the Aphekom project during 1990–2008. Poisson regression was used to estimate the city-specific risks of death associated with changes in SO2 concentrations for the time periods before legislation and subsequent periods following the implementation of the three European Directives. City-specific risk estimates were pooled using meta-regression. We also estimated the health impact associated with changes in SO2 concentrations during these pre-and post-implementation periods. During the study period, 10 μg/m3 increases in SO2 levels were associated with increases in all-cause (0.53 %), respiratory (0.49 %) and cardiovascular (0.72 %) mortality. We found no evidence of changes in the SO2 concentration–response function across the implementation periods. We estimated, annually, a total of 639, 1,093 and 1,616 premature deaths across the 14 EU cities as result of respective reductions in SO2 concentrations in each of the three implementation periods. Our study suggests that the linear relationship between daily SO2 concentrations and mortality has remained unaltered despite substantial reductions in ambient concentrations in recent years arising from EU directives to limit sulphur content in fuel. This linearity suggests that new legislation to reduce SO2 concentrations further will bring about additional public health benefits.

This study reports on the assessment of a multivariate heat wave vulnerability index (HVI) developed for London, United Kingdom. The HVI is assessed in terms of its ability to predict whether mortality and ambulance callout attain above average levels during heat wave events. Three approaches to assessment were adopted: 1) calculation of categorical statistics and associated skill scores for the dichotomous situation that above average mortality or ambulance callout occurred or not, 2) the degree to which relative risk of the aforementioned health outcomes changed with an increase in heat vulnerability as established using Poisson regression analysis, and 3) an independent samples test of the difference of mean mortality and ambulance callout between census units with and without high heat exposure and high vulnerability. The assessment results reveal that the HVI and a simple single variable index that represents age as a heat risk factor (the elderly index) offer potential as a priori indicators of the level of ambulance callout and mortality for all summer days and heat wave events, respectively. Based on the assessment results the utility of the HVI for heat risk management is discussed.

Heat waves and air pollution are both associated with increased mortality. Their joint effects are less well understood.We explored the role of air pollution in modifying the effects of heat waves on mortality, within the EuroHEAT project. Daily mortality, meteorologic, and air pollution data from nine European cities for the years 1990-2004 were assembled. We defined heat waves by taking both intensity and duration into account. The city-specific effects of heat wave episodes were estimated using generalized estimating equation models, adjusting for potential confounders with and without inclusion of air pollutants (particles, ozone, nitrogen dioxide, sulphur dioxide, carbon monoxide). To investigate effect modification, we introduced an interaction term between heat waves and each single pollutant in the models. Random effects meta-analysis was used to summarize the city-specific results.The increase in the number of daily deaths during heat wave episodes was 54% higher on high ozone days compared with low, among people age 75-84 years. The heat wave effect on high PM10 days was increased by 36% and 106% in the 75-84 year and 85+ year age groups, respectively. A similar pattern was observed for effects on cardiovascular mortality. Effect modification was less evident for respiratory mortality, although the heat wave effect itself was greater for this cause of death. The heat wave effect was smaller (15-30%) after adjustment for ozone or PM10.The heat wave effect on mortality was larger during high ozone or high PM10 days. When assessing the effect of heat waves on mortality, lack of adjustment for ozone and especially PM10 overestimates effect parameters. This bias has implications for public health policy.

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 as active transforming growth factor-beta (TGF-β) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12 months. 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 1 pg/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-β, 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.

The precise pathogenetic mechanisms and the potential role of uncontrolled fibroblastic proliferation or occult infection in IPF acute exacerbations need clarification. The aim of the study was the assessment of profibrotic and proinflammatory profile in both stable and excacerbated patients and their association to outcome. Stable or exacerbated patients referred to our department from October 2013 until November 2014 were included. IL-6, IL-8 and TGF-b were measured. All patients were followed up for 12 months. Tobit and logistic regression analysis were applied. Forty-one patients were included in the study [18 exacerbated, median age (IQR) 68.5 (67.0, 78.0) and 23 with stable IPF, median age (IQR) 71.0 (69.0, 74.0)]. Exacerbated patients presented higher plasma levels of IL-6 and IL-8 compared to those with stable IPF [median (IQR) 6.2 (3.2, 26.5) vs 2.1 (1.0, 4.4) pg/ml, p=0.002; median (IQR) 16.5 (12.9, 44.8) vs 10.1 (7.9, 13.2) pg/ml, p=0.046, respectively]. Most of the differences were independent to age, smoking status, procalcitonin, CRP, corticosteroid and oxygen treatment. No significant differences were observed in the profibrotic cytokine TGF-b between the two groups. An increase of IL-6 or IL-8 by 1 pg/ml increased the odds of death by 5,6% (p=0.021) and 6,7% (p=0.013) respectively in all patients and by 3,8% (p=0.093) and 4,3% (p=0.078) in exacerbated patients. The increased plasma levels of IL-6 and IL-8 found in exacerbated patients compared to stable suggest the presence of inflammation that may also relate to occult infection. Furthermore, our results indicate that plasma levels of IL-6 and IL-8 are associated with increased risk of death in all.

Introduction: High temperatures and heat waves are associated with large increases in mortality, especially among susceptible individuals living in urban areas. Although large multi-city studies ha...

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

There is ample evidence of adverse associations between short-term exposure to ambient particle mass concentrations and health but little is known about the relative contribution from various sources.We used air particle composition and number networks in London between 2011 and 2012 to derive six source-related factors for PMWe found no evidence of associations between PMOur findings are broadly consistent with the growing evidence of the toxicity of traffic and combustion particles, particularly in relation to respiratory morbidity in children and cardiovascular morbidity in younger adults.

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.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.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%.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.

Dental implants in partially edentulous patients are a predictable therapeutic option. In patients with reduced bone volume, tooth-to-implant connected prostheses have been described as a treatment option. In this systematic review, the incidence of biologic and technical complications and the long-term survival rates of tooth-implant supported fixed partial dentures (FPDs) are analyzed. In cases where a natural tooth is connected with an implant to support a FPD, a rigid connection should be preferred.

The climate and vegetation of the greater Athens area (population over three million) make forest fires a real threat to the environment during the summer. A few studies have reported the adverse health effects of forest fires, mainly using morbidity outcomes. The authors investigated the short-term effects of forest fires on non-accidental mortality in the population of Athens, Greece, during 1998-2004.The authors used generalised additive models to investigate the effect of forest fires on daily mortality, adjusting for time trend and meteorological variables, taking into account air pollution as measured from fixed monitors. Forest fires were classified by size according to the area burnt.Small fires do not have an effect on mortality. Medium sized fires are associated with an increase of 4.9% (95% CI 0.3% to 9.6%) in the daily total number of deaths, 6.0% (95% CI -0.3% to 12.6%) in the number of cardiovascular deaths and 16.2% (95% CI 1.3% to 33.4%) in the number of respiratory deaths. Cardiovascular effects are larger in those aged75 years, while respiratory effects are larger in older people. The corresponding effects of the one large fire are: 49.7% (95% CI 37.2% to 63.4%), 60.6% (95% CI 43.1% to 80.3%) and 92.0% (95% CI 47.5% to 150.0%). These effects cannot be completely explained by an increase in ambient particle concentrations.Forest fires have an immediate effect on mortality, not associated with accidental deaths, which is a significant public health problem, especially if the fire occurs near a densely populated area.

BACKGROUND: Epidemiologic studies show that high temperatures are related to mortality, but little is known about the exposure-response function and the lagged effect of heat. We report the associations between daily maximum apparent temperature and daily deaths during the warm season in 15 European cities. METHODS: The city-specific analyses were based on generalized estimating equations and the city-specific results were combined in a Bayesian random effects meta-analysis. We specified distributed lag models in studying the delayed effect of exposure. Time-varying coefficient models were used to check the assumption of a constant heat effect over the warm season. RESULTS: The city-specific exposure-response functions have a V shape, with a change-point that varied among cities. The meta-analytic estimate of the threshold was 29.4 degrees C for Mediterranean cities and 23.3 degrees C for north-continental cities. The estimated overall change in all natural mortality associated with a 1 degrees C increase in maximum apparent temperature above the city-specific threshold was 3.12% (95% credibility interval = 0.60% to 5.72%) in the Mediterranean region and 1.84% (0.06% to 3.64%) in the north-continental region. Stronger associations were found between heat and mortality from respiratory diseases, and with mortality in the elderly. CONCLUSIONS: There is an important mortality effect of heat across Europe. The effect is evident from June through August; it is limited to the first week following temperature excess, with evidence of mortality displacement. There is some suggestion of a higher effect of early season exposures. Acclimatization and individual susceptibility need further investigation as possible explanations for the observed heterogeneity among cities.

The authors investigated whether neutrophil to lymphocyte ratio (N/L) can contribute to the diagnosis and risk assessment in patients with type A acute aortic dissection (AAD).The authors studied 120 consecutive patients with type A AAD (group I) and compared them with 121 consecutive patients with chronic aneurysms (group II) and 121 age- and sex-matched healthy subjects (group III).It was found that white blood cell count, N/L, D-dimer and C-reactive protein were significantly higher in group I versus both groups II and III (p0.001 for all comparisons). White blood cell count and D-dimer were much higher in patients who died compared to survivors in group I (p = 0.023 and p = 0.033, respectively). A cutoff value of N/L4.6 was associated with 0.89 sensitivity and 0.91 specificity for AAD.High N/L may contribute to the diagnostic evaluation and prompt immediate therapy in patients with type A AAD.

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/m3, 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.

In the Air Pollution and Health: A European Approach (APHEA2) project, the effects of ambient ozone concentrations on mortality were investigated. Data were collected on daily ozone concentrations, the daily number of deaths, confounders, and potential effect modifiers from 23 cities/areas for at least 3 years since 1990. Effect estimates were obtained for each city with city-specific models and were combined using second-stage regression models. No significant effects were observed during the cold half of the year. For the warm season, an increase in the 1-hour ozone concentration by 10 mug/ml was associated with a 0.33% (95% confidence interval [CI], 0.17-0.52) increase in the total daily number of deaths, 0.45% (95% CI, 0.22-0.69) in the number of cardiovascular deaths, and 1.13% (95% CI, 0.62-1.48) in the number of respiratory deaths. The corresponding figures for the 8-hour ozone were similar. The associations with total mortality were independent of SO2 and particulate matter with aerodynamic diameter less than 10 mum (PM10) but were somewhat confounded by NO2 and CO. Individual city estimates were heterogeneous for total (a higher standardized mortality rate was associated with larger effects) and cardiovascular mortality (larger effects were observed in southern cities). The dose-response curve of ozone effects on total mortality during the summer did not deviate significantly from linearity.

Purpose Breastfeeding is the best way to feed all infants, but not all infants can be (exclusively) breastfed. Cow's milk based infant formula is the second choice infant feeding. Methods The safety of a new synbiotic infant formula, supplemented with Bifidobacterium lactis and fructo-oligosaccharides, with lactose and a whey/casein 60/40 protein ratio was tested in 280 infants during 3 months. Results The median age of the infants at inclusion was 0.89 months. Weight evolution was in accordance with the World Health Organization growth charts for exclusive breastfed infants. The evolution of all anthropometric parameters (weight-for-length z score and body mass index-for-age z score) was within the normal range. The incidence of functional constipation (3.2%), daily regurgitation (10.9%), infantile crying and colic (10.5%) were all significantly lower than the reported median prevalence for a similar age according to literature (median value of 7.8% for functional constipation, 26.7% for regurgitation, 17.7% for infantile colic). Conclusion The new synbiotic infant starter formula was safe, resulted in normal growth and was well tolerated. Functional gastro-intestinal manifestations (functional constipation, regurgitation and colic) were significantly lower than reported in literature. Synbiotics (Bifidobacterium lactis and fructo-oligosaccharides) in cow's milk based infant formula bring the second choice infant feeding, formula, closer to the golden standard, exclusive breastfeeding.

PURPOSE: The purpose of this paper is to evaluate the efficacy of a lactose- reduced synbiotic partial whey hydrolysate in formula fed infants presenting with colic and the impact of this dietary intervention in mean crying time and quality of life. METHODS: Forty infants with infantile colic were treated during one month with parental reassurance and the intervention formula (partial whey hydrolysate, reduced lactose, Bifidobacterium lactis BB12 and galacto-oligosaccharides) and were compared to a control group of 20 infants with infantile colic treated with parental reassurance and a standard infant formula. Parents completed a quality of life (QoL) questionnaire assessing the burden of infantile colic. Wilcoxon test, t-test and Mann-Whitney test were used to compare QoL scores before and after intervention as well as between the intervention and control group. RESULTS: At inclusion, duration of crying did not differ between both groups. Crying duration decreased with 2.7 hours (from 3.2 to 0.5 hours) in the intervention group while duration of crying decreased only with 1.2 hours in the control group (p

Background: Although numerous studies have shown that high temperatures are related to increases in mortality, little research has investigated how the effect varies over time in response to change...

AIM: To present and integrate findings of studies investigating the effects of laparoscopic cholecystectomy on various aspects of lung function. METHODS: We extensively reviewed literature of the past 24 years concerning the effects of laparoscopic cholecystectomy in comparison to the open procedure on many aspects of lung function including spirometric values, arterial blood gases, respiratory muscle performance and aspects of breathing control, by critically analyzing physiopathologic interpretations and clinically important conclusions. A total of thirty-four articles were used to extract information for the meta-analysis concerning the impact of the laparoscopic procedure on lung function and respiratory physiopathology. The quality of the literature reviewed was evaluated by the number of their citations and the total impact factor of the corresponding journals. A fixed and random effect meta-analysis was used to estimate the pooled standardized mean difference of studied parameters for laparoscopic (LC) and open (OC) procedures. A crude comparison of the two methods using all available information was performed testing the postoperative values expressed as percentages of the preoperative ones using the Mann-Whitney two-sample test. RESULTS: Most of the relevant studies have investigated and compared changes in spirometric parameters.The median percentage and interquartile range (IQR) of preoperative values in forced vital capacity (FVC), forced expiratory volume in 1 s and forced expiratory flow (FEF) at 25%-75% of FVC (FEF25%-75%) expressed as percentage of their preoperative values 24 h after LC and OC were respectively as follows: [77.6 (73.0, 80.0) L vs 55.4 (50.0, 64.0) L, P < 0.001; 76.0 (72.3, 81.0) L vs 52.5 (50.0, 56.7) L, P < 0.001; and 78.8 (68.8, 80.9) L/s vs 60.0 (36.1, 66.1) L/s, P = 0.005]. Concerning arterial blood gases, partial pressure of oxygen [PaO2 (kPa)] at 24 or 48 h after surgical treatment showed reductions that were significantly greater in OC compared with LC [LC median 1.0, IQR (0.6, 1.3); OC median 2.4, IQR (1.2, 2.6), P = 0.019]. Fewer studies have investigated the effect of LC on respiratory muscle performance showing less impact of this surgical method on maximal respiratory pressures (P < 0.01); and changes in the control of breathing after LC evidenced by increase in mean inspiratory impedance (P < 0.001) and minimal reduction of duty cycle (P = 0.01) compared with preoperative data. CONCLUSION: Laparoscopic cholecystectomy seems to be associated with less postoperative derangement of lung function compared to the open procedure.