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Background: Mutations and deregulations in components of the Hedgehog (Hh) pathway have been associated with cancer onset and tumor growth in different malignancies, but their role in non-small cell lung cancer (NSCLC) remains unclear. This study aims to investigate the expression pattern of the main components of the Hh pathway in tumor and adjacent normal tissue biopsies of resected NSCLC patients., Methods: The relative expression of GLI1, PTCH1, SHH, and SMO was analyzed by quantitative polymerase chain reaction (PCR) in a cohort of 245 NSCLC patients. Results were validated in an independent cohort of NSCLC patients from The Cancer Genome Atlas (TCGA)., Results: We found that SMO and GLI1 were overexpressed in the tumor compared with normal-paired tissue, whereas PTCH1 and SHH were underexpressed. In addition, patients with higher expression levels of PTCH1 presented better outcomes. A gene expression score, called the Hedgehog Score, was calculated using a multivariable model including analyzed components of the Hh signaling pathway. NSCLC patients with a high Hedgehog Score had significantly shorter relapse-free survival (RFS) and overall survival (OS) than patients with a low score, especially at stage I of the disease. Similarly, patients in the adenocarcinoma (ADC) subcohort had shorter RFS and OS. Multivariate Cox analysis exhibited that the Hedgehog Score is an independent prognostic biomarker for OS in both the entire training cohort and the ADC subcohort. The Hedgehog Score was validated in an independent cohort of NSCLC patients from TCGA, which confirmed its prognostic value., Conclusions: Our results provide relevant prognostic data for NSCLC patients and support further studies on the Hh pathway., (© 2022. Society of Surgical Oncology.)

Objectives: The present study was designed to compare outcomes in patients undergoing thoracic surgery using the VivaSight double-lumen tube (VDLT) or the conventional double-lumen tube (cDLT)., Design: A retrospective analysis of 100 patients scheduled for lung resection recruited over 21 consecutive months (January 2018-September 2019)., Setting: Single-center university teaching hospital investigation., Participants: A randomized sample of 100 patients who underwent lung resection during this period were selected for the purpose to compare 50 patients in the VDLT group and 50 in the cDLT group., Interventions: After institutional review board approval, patients were chosen according to inclusion and exclusion criteria and we created a general database. The 100 patients have been chosen through a random process with the Microsoft Excel program (Microsoft 2018, Version 16.16.16)., Measurements and Main Results: The primary endpoint of the study was to analyze the need to use fiberoptic bronchoscopy to confirm the correct positioning of VDLT or the cDLT used for lung isolation. Secondary endpoints were respiratory parameters, admission to the intensive care unit, length of hospitalization, postoperative complications, readmission, and 30-day mortality rate. The use of fiberoptic bronchoscopy was lower in the VDLT group, and the size of the tube was smaller. The intraoperative respiratory and hemodynamics parameters were optimal. There were no other preoperative, intraoperative, or postoperative differences between both groups., Conclusions: The VDLT reduces the need for fiberoptic bronchoscopy, and it seems that a smaller size is needed. Finally, VDLT is cost-effective using disposable fiberscopes.

Lung cancer is a malignant disease with high mortality and poor prognosis, frequently diagnosed at advanced stages. Nowadays, immense progress in treatment has been achieved. However, the present scenario continues to be critical, and a full comprehension of tumor progression mechanisms is required, with exosomes being potentially relevant players. Exosomes are membranous vesicles that contain biological information, which can be transported cell-to-cell and modulate relevant processes in the hallmarks of cancer. The present research aims to characterize the exosomes' cargo and study their role in NSCLC to identify biomarkers. We analyzed exosomes secreted by primary cultures and cell lines, grown in monolayer and tumorsphere formations. Exosomal DNA content showed molecular alterations, whereas RNA high-throughput analysis resulted in a pattern of differentially expressed genes depending on histology. The most significant differences were found in XAGE1B, CABYR, NKX2-1, SEPP1, CAPRIN1, and RIOK3 genes when samples from two independent cohorts of resected NSCLC patients were analyzed. We identified and validated biomarkers for adenocarcinoma and squamous cell carcinoma. Our results could represent a relevant contribution concerning exosomes in clinical practice, allowing for the identification of biomarkers that provide information regarding tumor features, prognosis and clinical behavior of the disease.

Despite the success of immunotherapies in lung cancer, development of new biomarkers for patient selection is urgently needed. This study aims to explore minimally invasive approaches to characterize circulating T cell receptor beta chain (TCR-β) repertoire in a cohort of advanced non-small cell lung cancer (NSCLC) patients treated with first-line pembrolizumab. Peripheral blood samples were obtained at two time points: i) pretreatment (PRE) and ii) first response assessment (FR). Next-generation sequencing (NGS) was used to analyze the hypervariable complementary determining region 3 (CDR3) of TCR-β chain. Richness, evenness, convergence, and Jaccard similarity indexes plus variable (V) and joining (J)-gene usage were studied. Our results revealed that increased richness during treatment was associated with durable clinical benefit (DCB; p = 0.046), longer progression-free survival (PFS; p = 0.007) and overall survival (OS; p = 0.05). Patients with Jaccard similarity index ≥0.0605 between PRE and FR samples showed improved PFS ( p = 0.021). Higher TRBV20-1 PRE usage was associated with DCB ( p = 0.027). TRBV20-1 levels ≥9.14% in PRE and ≥9.02% in FR significantly increased PFS ( p = 0.025 and p = 0.016) and OS ( p = 0.035 and p = 0.018). Overall, analysis of circulating TCR-β repertoire may provide information about the immune response in anti-PD-1 treated NSCLC patients; in this scenario, it can also offer important information about the clinical outcome.

The cleaving of a novel microstructured polymer optical fiber (mPOF) to obtain an acceptable connectorized fiber end-face is studied. The effect of the blade temperature and the speed of the cutting blade on the end-face is qualitatively assessed. Recently manufactured mPOFs with air-structured 3- and 4-ring hexagonal-like hole cladding structures with outer fiber diameters of around 250 μm are employed. Good quality end-faces can be obtained by cleaving mPOF fibers at room temperature for blade temperatures within the range 60-80 °C and at a low blade speed at 0.5 mm/s. The importance of the blade surface quality is also addressed, being a critical condition for obtaining satisfactory mPOF end-faces after cleaving. From our experiments, up to four fiber cuts with the same razor blade and blade surface can be carried out with acceptable and similar fiber end-face results.

Introduction: PD1/PD-L1 pathway targeting therapies are nowadays an established treatment option for patients with NSCLC. We assessed whether PD-L1 expression in NSCLC tumor cells was associated with specific clinical features or overall survival using four different clones., Methods and Results: A retrospective study included formalin-fixed paraffin embedded (FFPE) surgical tumors from 482 patients. PD-L1 status was assessed with immunohistochemistry in tumor cells on tissue microarrays using clones 28-8, 22C3, SP263 and SP142. Associations with OS were assessed by Kaplan-Meier and multivariate Cox's regression analysis. Patients' median age: 68 years (39-86); histology: adenocarcinoma (AdCa) 61%, squamous-cell carcinoma (SqCC) 33%, and large cell carcinoma (LCC) 6%; p-stage: IA (46%), IB (30%), IIA (10%), IIB (11,4%), IIIA (1,2%), IIIB - IV (0,4%). PD-L1 positivity (≥1%) in NSCLC for clones 28-8, 22C3, SP263, SP142 was 41.5%, 34.2%, 42.7%, 10.4%, respectively (Pearson Chi-square p < 0.0001). PD-L1 expression was correlated with histology, tumor size and grading. Statistically significant association between PD-L1 expression and OS in NSCLC and Non-AdCa was observed with clone SP142 (log-rank p = 0.045 and p = 0.05, respectively). Statistically significant association between PD-L1 expression and OS in LCC was observed with clones 22C3 (log-rank p = 0.009) and SP263 (log-rank p = 0.050)., Conclusions: Overexpression of the PD-L1 clone SP142 was associated with poor overall survival in NSCLC and Non-AdCa. Clones 22C3 and SP263 were associated with poor prognosis in LCC. PD-L1 status might serve as a prognostic marker in NSCLC., (Copyright © 2021. Published by Elsevier Inc.)

The development of metabolic syndrome negatively affects the quality of life of people with serious mental illness. Experts agree on the need to evaluate the physical health of patients and intervene in modifiable risk factors, with emphasis on the promotion of healthy lifestyles. Interventions should include nutritional counselling and physical activity. This 24-week randomized trial evaluated the effects of a community-based nurse-led lifestyle-modification intervention in people with serious mental illness meeting metabolic syndrome criteria, and its impact on health-related quality of life and physical activity. Sixty-one participants from two community mental health centres were randomly assigned to the intervention or control group. The intervention consisted of weekly group sessions, with 20 min of theoretical content and 60 min of nurse-led physical activity. Postintervention results between groups showed no differences in weight, waist circumference, fasting glucose, and systolic blood pressure. Differences in body mass index, triglyceride concentrations, and diastolic blood pressure were found to be significant (P = 0.010, P = 0.038, and P = 0.017). Participants who performed the intervention reported an increase in physical activity, which did not occur in the control group (P = 0.035), and also reported better health status (P < 0.001). Our intervention showed positive effects reducing participants' cardiovascular and metabolic risks and improving their physical activity and quality of life. To our knowledge, this is the first clinical trial led and carried out by mental health nurses in community mental health centres which takes into account the effects of a lifestyle intervention on every metabolic syndrome criterion, health-related quality of life, and physical activity., (© 2019 Australian College of Mental Health Nurses Inc.)

Coastal ecosystems are heavily polluted by human activities. These pollutants reach the aquatic environment and accumulate in the sediment. Among the chemical pollutants, metals represent a notable hazard since they are not biodegradable and have the capability to bioaccumulate, resulting in toxic effects in both the short and long term. In this study, the content of metals and As in marine sediments of the Spanish Mediterranean coast was determined. A total of four annual sampling campaigns were carried out along the Valencian Community coastline, where the presence of eight trace elements (Cr, Cd, Ni, Pb, Cu, Hg, Zn and As) was determined. In this area, the presence of the contaminants is due to both natural and anthropogenic sources. The results obtained allowed, first, to establish nearness Reference Values of the area under study, second, to use several pollution indices (Contamination Factor, Enrichment Factor, Geoaccumulation Factor, Nemerow Pollution Index, and Modified Pollution Index) to determine contamination levels in the area, and finally to select the best index to apply in this coastal zone. The best indices to use in this region are EF and MPI since both take into consideration the natural contributions of the elements studied. The results revealed that according to the index used only two studied zones are classified as Heavily and Severely polluted. The remaining zones (between 25 and 29%) were classified as Moderately or Moderately to Heavily polluted and most of the zones (63% to 100%) were classified as Unpolluted/Low Polluted and Unpolluted/Slightly Polluted. The outcomes obtained with this work indicate that in general, the Valencian coast does not present significant levels of pollution due to the studied trace elements., (Copyright © 2019. Published by Elsevier B.V.)

The Water Framework Directive (WFD, 2000/60/EC) determines that all water bodies must achieve a good ecological status. The solar salterns system of Mata-Torrevieja (Spain) has been designated as Heavily Modified Water Bodies (HMWB). This ecosystem is a transitional water body (TW) largely conditioned by socio-economic management plan and the related human activities that take place. Thus, WFD establishes as obligatory the determination of their ecological potential, and not their ecological status. In order to define the ecological potential, it is necessary to determine previously the chemical and biological conditions of the water body. This paper is focused on the analysis of physical-chemical parameters of a saltern system during 2008-2016, in order to establish a starting point for the implementation process of the WFD in this type of ecosystem (TW-HMWB). The behavior of salinity and physical-chemical parameters (temperature, pH, nutrients) has been studied. Salinity was the most relevant parameter studied to define pressures for these water bodies. However, total phosphorus turned out to be a good potential status indicator. It would be one of the most suitable chemical parameters to propose a methodology for the determination of the ecological potential in the salterns., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were established, using sphere-forming assays for CSC enrichment and adherent conditions for the control counterparts. Patient-derived tumorspheres showed self-renewal and unlimited exponential growth potentials, resistance against chemotherapeutic agents, invasion and differentiation capacities in vitro, and superior tumorigenic potential in vivo. Using quantitative PCR, gene expression profiles were analyzed and NANOG, NOTCH3, CD44, CDKN1A, SNAI1, and ITGA6 were selected to distinguish tumorspheres from adherent cells. Immunoblot and immunofluorescence analyses confirmed that proteins encoded by these genes were consistently increased in tumorspheres from adenocarcinoma patients and showed differential localization and expression patterns. The prognostic role of genes significantly overexpressed in tumorspheres was evaluated in a NSCLC cohort (N = 661) from The Cancer Genome Atlas. Based on a Cox regression analysis, CDKN1A, SNAI1, and ITGA6 were found to be associated with prognosis and used to calculate a gene expression score, named CSC score. Kaplan-Meier survival analysis showed that patients with high CSC score have shorter overall survival (OS) in the entire cohort [37.7 vs. 60.4 months (mo), p = 0.001] and the adenocarcinoma subcohort [36.6 vs. 53.5 mo, p = 0.003], but not in the squamous cell carcinoma one. Multivariate analysis indicated that this gene expression score is an independent biomarker of prognosis for OS in both the entire cohort [hazard ratio (HR): 1.498; 95% confidence interval (CI), 1.167-1.922; p = 0.001] and the adenocarcinoma subcohort [HR: 1.869; 95% CI, 1.275-2.738; p = 0.001]. This score was also analyzed in an independent cohort of 114 adenocarcinoma patients, confirming its prognostic value [42.90 vs. not reached (NR) mo, p = 0.020]. In conclusion, our findings provide relevant prognostic information for lung adenocarcinoma patients and the basis for developing novel therapies. Further studies are required to identify suitable markers and targets for lung squamous cell carcinoma patients.

The anthropogenic alteration of the nitrogen cycle results in the modification of the whole food web. And yet, the impact caused on nitrogen dynamics in marine systems is still very uncertain. We propose a workflow to evaluate changes to coastal nitrification by modelling nitrite dynamics, the intermediary compound. Nitrite concentrations were estimated with a simple steady state nitrification model, which was calibrated in 9 NW Mediterranean coastal sites with different anthropogenic pressures, located within 250 km. The results obtained indicate that nitrite peaks are observed in winter and explained by nitrification response to temperature, but these dynamics are altered in impacted coastal waters. We found the second step of nitrification to be more sensitive to temperature, which entails a significant impact of climate change on the decoupling of the two steps of nitrification. The results could be extrapolated to numerous coastal regions of the Mediterranean Sea with similar characteristics., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ecosystem-based management is one of the strategies to protect the coastal areas. One of the key elements is phytoplankton community composition since it represents a good indicator of anthropogenic pressures. This identifies the seasonal patterns of phytoplankton, and its alterations by the stress factors induced by human activities are highly valuable. This research represents the first attempt to study that 476 km of western Mediterranean coastal belongs to the Valencian Community (Spain) based on the phytoplankton composition approach. The water samples during a 5-year period (6757 water samples) were taken to determine its phytoplankton group's dynamics and its relationship with anthropogenic stressors by means of a series of plots and statistical analyses. Diatoms are the group that most contribute to the whole community composition with two periods of maximum abundance. The Prasinophyceae and Cryptophyceae show unimodal patterns varying its maximum values depending on the season. The picocyanobacteria group exhibited the clearest and best-defined pattern. Other groups have no clear seasonal pattern and become abundant in areas of higher anthropogenic pressure. Graphical abstract Figure A contains poor quality of text in image. Otherwise, please provide replacement figure file.A new graphical abstract, with higher quality is attached.

A comprehensive study was carried out to evaluate the occurrence, significance of concentrations and spatial distribution of heavy metals (Cr, Cd, Ni, Cu, Pb, Hg, Zn and As) in sediments along the Valencia coastline (Spain). The sampling campaign covered 476 km of the coastline in a 4-year period. The highest concentrations of metals in the sediments were mainly Cr, Ni, Zn and Cd (up to 28.93 mg Cr kg -1 dw, 15.80 mg Ni kg -1 dw, 57.13 mg Zn kg -1 dw and 0.293 mg Cd kg -1 dw), obtained in the northern areas, some central areas and in an isolated area on the southern coastline. The Sediment Quality Guidelines applied reveal that for all metals studied, none of them reached, or exceed, the "effects of median range" or the "probable effect level". The pollution index reveals that 75% of the stretch coastline has a low priority risk level and the rest "medium-low priority risk level". And, lastly, Potential Ecological Risk Index shows that all but one zone have low ecological risk.

Background: Carcinoids now constitute complex tumours which require a multidisciplinary approach and long-term follow-up. Surgical intervention is nowadays confirmed as the mainstay of treatment., Methods: From 1980 to 2015, EMETNE-SEPAR collected 1,339 patients treated surgically for bronchial carcinoid (1,154 typical and 185 atypical carcinoids). Standard and conservative procedures were considered with regard to surgical approach. All the patients with carcinoid were pathologically coded following the standards of the 7 th edition 2009 TNM lung cancer staging. Statistical analyses were performed in order to determine whether histology, nodal affectation and surgical technique were associated with significant differences in survival, presence of metastases and local recurrence., Results: The influence of the surgical procedure on overall survival, the presence of metastases and local recurrence were demonstrated as no significant in our sample in central tumours (P>0.05). Sublobar resections in peripheral tumours are related to a decrease in survival in typical carcinoids (P=0.008) with nodal involvement and an increased number of recurrences in atypical carcinoids without nodal involvement (P=0.018)., Conclusions: In central typical carcinoid, the use of lung-sparing bronchoplastic techniques could influence local recurrence in some cases. This observation demands the intraoperative pathologic verification of an adequate surgical margin by frozen section. Peripheral typical carcinoids have been surgically treated, occasionally, by sublobar resection. However, in peripheral atypical carcinoid after a limited sublobar resection the observed increase of the probability of local recurrence makes it, in our opinion, not advisable., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: During lobectomy in patients with lung cancer, the operated lung is often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when the lung is re-expanded. We hypothesized that remote ischemic preconditioning (RIPC) would decrease oxidative lung damage and improve gas exchange in the postoperative period., Methods: We conducted a single-center, randomized, double-blind trial in patients with nonsmall cell lung cancer undergoing elective lung lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion induced by an ischemia cuff applied on the thigh) and/or control therapy without RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC) and arterial blood immediately after anesthesia induction and before RIPC and surgery (T0, baseline); during operated lung collapse, immediately before resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2); and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane levels in EBC at T1, T2, and T3. Secondary outcomes included the following: NO2+NO3, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2+NO3) and pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory index)., Results: Patients subjected to RIPC had lower EBC 8-isoprostane levels when compared with controls at T1, T2, and T3 (differences between means and 95% confidence intervals): -15.3 (5.8-24.8), P = .002; -20.0 (5.5-34.5), P = .008; and -10.4 (2.5-18.3), P = .011, respectively. In the RIPC group, EBC NO2+NO3 and H2O2 levels were also lower than in controls at T2 and T1-T3, respectively (all P < .05). Blood levels of 8-isoprostane and NO2+NO3 were lower in the RIPC group at T2 (P < .05). The RIPC group had better PaO2/FiO2 compared with controls at 2 hours, 8 hours, and 24 hours after lobectomy in 95% confidence intervals for differences between means: 78 (10-146), 66 (14-118), and 58 (12-104), respectively., Conclusions: Limb RIPC decreased EBC 8-isoprostane levels and other oxidative lung injury markers during lung lobectomy. RIPC also improved postoperative gas exchange as measured by PaO2/FiO2 ratio.

Background: The average five-year survival for non-small cell lung cancer (NSCLC) patients is approximately 15%. Emerging evidence indicates that microRNAs (miRNAs) constitute a new class of gene regulators in humans that may play an important role in tumorigenesis. Hence, there is growing interest in studying their role as possible new biomarkers whose expression is aberrant in cancer. Therefore, in this study we identified dysregulated miRNAs by next generation sequencing (NGS) and analyzed their prognostic value., Methods: Sequencing by oligo ligation detection technology was used to identify dysregulated miRNAs in a training cohort comprising paired tumor/normal tissue samples ( N = 32). We validated 22 randomly selected differentially-expressed miRNAs by quantitative real time PCR in tumor and adjacent normal tissue samples ( N = 178). Kaplan-Meier survival analysis and Cox regression were used in multivariate analysis to identify independent prognostic biomarkers., Results: NGS analysis revealed that 39 miRNAs were dysregulated in NSCLC: 28 were upregulated and 11 were downregulated. Twenty-two miRNAs were validated in an independent cohort. Interestingly, the group of patients with high expression of both miRNAs (miR-21 high and miR-188 high ) showed shorter relapse-free survival (RFS) and overall survival (OS) times. Multivariate analysis confirmed that this combined signature is an independent prognostic marker for RFS and OS ( p = 0.001 and p < 0.0001, respectively)., Conclusions: NGS technology can specifically identify dysregulated miRNA profiles in resectable NSCLC samples. MiR-21 or miR-188 overexpression correlated with a negative prognosis, and their combined signature may represent a new independent prognostic biomarker for RFS and OS., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflict of interest.

Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) ( n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm. Patients with higher expression levels of IL23A and LGALS2 presented better outcomes. In the clustering expression patterns, we observed that patients with higher expression of immunoregulatory genes had better survival rates. Additionally, these data were used to develop a gene expression score. Since CTLA4 and PD1 were associated with prognosis based on Cox regression analysis ( Z -score > 1.5), a multivariate model including these two genes was created. Absolute regression coefficients from this analysis were used in order to calculate the immune-checkpoint score: ( PD1 ×0.116) + ( CTLA4 ×0.059) for each case. Kaplan-Meier survival analysis showed that patients with high immune-checkpoint score have longer overall survival (OS) [NR vs. 40.4 mo, p = 0.008] and longer relapse-free survival (RFS) [82.6 vs. 23 mo, p = 0.009]. Multivariate analysis in the entire cohort indicated that the immune-checkpoint score was an independent biomarker of prognosis for OS [HR: 0.308; 95% CI, 0.156-0.609; p = 0.001] and RFS [HR: 0.527; 95% CI, 0.298-0.933; p = 0.028] in early-stage NSCLC patients. In conclusion, this score provides relevant prognostic information for a better characterization of early stage NSCLS patients with strikingly different outcomes and who may be candidates for immune-based therapies.

Background and Objective: We compared the incidence and outcome of pulmonary embolism (PE) in individuals with and without type 2 diabetes mellitus (T2DM) in Spain during 2004-2013., Methods: The study was based on National Hospital Discharge Data, and the study population comprised patients hospitalized for PE. Annual incidence rates were classified according to T2DM status. In-hospital mortality (IHM), length of hospital stay (LOHS), comorbidities and use of diagnosis and therapeutic procedures were analysed., Results: We identified 123 872 discharges of patients (56 361 men and 67 511 women) with PE as their primary diagnosis (15.3% with T2DM). Incidence of discharge diagnoses of PE increased significantly in all groups. Crude rates were higher in diabetic patients. A positive association was identified between T2DM and PE: adjusted IRR was 2.00 (95% CI: 1.95-2.05) for men and 2.50 (95% CI: 2.45-2.57) for women. LOHS, readmissions and IHM decreased significantly for both groups. An association between IHM and risk factors (older age, Charlson comorbidity index >3, atrial fibrillation and cancer) was observed. T2DM was associated with higher IHM in men (OR: 1.22, 95% CI: 1.12-1.32) and women (OR: 1.24, 95% CI: 1.15-1.33). The use of computed tomography pulmonary angiography increased significantly overtime., Conclusion: We confirmed that in both men and women, diabetes was an independent risk factor for IHM. The incidence of discharge of patients with PE increased significantly during the study period. Diabetic men and women had a higher risk of hospitalization for PE than non-diabetic men and women. Diabetic women had higher IHM than diabetic men., (© 2016 Asian Pacific Society of Respirology.)

Objectives: During lung lobectomy, the operated lung completely collapses with simultaneous hypoxic pulmonary vasoconstriction, followed by expansion and reperfusion. Here, we investigated glutathione oxidation and lipoperoxidation in patients undergoing lung lobectomy, during one-lung ventilation (OLV) and after resuming two-lung ventilation (TLV), and examined the relationship with OLV duration., Methods: We performed a single-centre, observational, prospective study in 32 patients undergoing lung lobectomy. Blood samples were collected at five time-points: T0, pre-operatively; T1, during OLV, 5 minutes before resuming TLV; and T2, T3, and T4, respectively, 5, 60, and 180 minutes after resuming TLV. Samples were tested for reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione redox potential, and malondialdehyde (MDA)., Results: GSSG and MDA blood levels increased at T1, and increased further at T2. OLV duration directly correlated with marker levels at T1 and T2. Blood levels of GSH and glutathione redox potential decreased at T1-T3. GSSG, oxidized glutathione/total glutathione ratio, and MDA levels were inversely correlated with arterial blood PO2/FiO2 at T1 and T2., Discussion: During lung lobectomy and OLV, glutathione oxidation, and lipoperoxidation marker blood levels increase, with further increases after resuming TLV. Oxidative stress degree was directly correlated with OLV duration, and inversely correlated with arterial blood PO2/FiO2.

The prognosis of non-small cell lung cancer (NSCLC) remains poor and heterogeneous and new biomarkers are needed. As the immune system plays a pivotal role in cancer, the study of immune-related markers may provide valuable prognostic information of NSCLC. In 122 formalin-fixed, paraffin-embedded tumor tissue samples from early-stage NSCLC, tumor and tumor-near stromal areas were microdissected and gene expression levels of conventional and regulatory T cell markers were assessed by quantitative polymerase chain reaction. Also, the presence of infiltrating CD4+, CD8+, and FOXP3+ cells in tumor samples was assessed by immunohistochemistry. The relative proportion of conventional and regulatory T cells present in the tumor environment was assessed and found to be key to understand the importance that the immune system analysis has in the prognostics of NSCLC patients. The presence of CD8+ cells in the tumor compartment was associated with better outcome, whereas the presence of FOXP3+ cells was associated with worse overall survival. The negative prognostic value of combined biomarkers, indicating high levels of FOXP3 in the stroma and low levels of CD4 or CD8 in tumors, was observed at mRNA level and was validated by immunohistochemistry.In conclusion, the proportion of T helper and cytotoxic cells vs. regulatory T cells in different locations of the tumor microenvironment have opposite prognostic impacts in resected NSCLC., Competing Interests: The authors declare no conflict of interest.

Background: Venous and arterial thrombosis share a number of pathogenic mechanisms, but the burden of pulmonary embolism (PE) has not been consistently compared with that in other arterial diseases., Methods: We used the Spanish National Discharge Database to compare the frequency, clinical characteristics and mortality rate of all patients with PE, acute coronary syndrome (ACS) or ischemic stroke admitted from 2001 to 2010. Patients were classified as having primary diagnosis (the process leading to hospital admission) or secondary diagnosis (it appeared during hospital stay for other reasons), Results: During the study period, 31,949,739 patients were discharged. Of these, 165,229 (0.52%) were diagnosed with PE, 562,837 (1.76%) with ACS and 495,427 (1.55%) with ischemic stroke. Overall, 31% of patients with PE, 8.4% with ACS and 13% with ischemic stroke had secondary diagnoses. The most common reasons for admission in patients with secondary PE were: cancer (21%), acute respiratory failure (11%), acute heart failure (6.4%) and stroke (5.5%). Mean hospital stay was: 14 ± 13 days in PE patients, 9.7 ± 9.7 in those with ACS and 13 ± 14 days in those with stroke. In-hospital mortality rate was: 10.5%, 10.1% and 12.3% respectively in patients with primary diagnosis, and 36%, 34% and 29% in those with secondary diagnosis., Conclusions: Patients hospitalized with PE were 3-4 times less frequent than those with ACS or stroke, but had a higher mortality. One in every 3 patients with PE (but only one in every 10 with ACS or stroke) had secondary diagnosis, and these patients had the highest mortality., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Despite advances in hospital management in recent years, it is not clear whether mortality after acute pulmonary embolism (PE) has decreased over time., Objectives: This study describes the trends in the management and outcomes of acute symptomatic PE., Methods: We identified adults with acute PE enrolled in the registry between 2001 and 2013. We assessed temporal trends in length of hospital stay and use of pharmacological and interventional therapies. Using multivariable regression, we examined temporal trends in risk-adjusted rates of all-cause and PE-related death to 30 days after diagnosis., Results: Among 23,858 patients with PE, mean length of stay decreased from 13.6 to 9.3 days over time (32% relative reduction, p < 0.001). For initial treatment, use of low-molecular-weight heparin increased from 77% to 84%, whereas the use of unfractionated heparin decreased from 22% to 8.4% (p < 0.001 for trend for all comparisons). Thrombolytic therapy use increased from 0.7% to 1.0% (p = 0.07 for trend) and surgical embolectomy use doubled from 0.3% to 0.6% (p < 0.01 for trend). Risk-adjusted rates of all-cause mortality decreased from 6.6% in the first period (2001 to 2005) to 4.9% in the last period (2010 to 2013) (p = 0.02 for trend). Rates of PE-related mortality decreased over time, with a risk-adjusted rate of 3.3% in 2001 to 2005 and 1.8% in 2010 to 2013 (p < 0.01 for trend)., Conclusions: In a large international registry of patients with PE, improvements in length of stay and changes in the initial treatment were accompanied by a reduction in short-term all-cause and PE-specific mortality., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: During lung lobectomy, the operated lung is collapsed and hypoperfused; oxygen deprivation is accompanied by reactive hypoxic pulmonary vasoconstriction. After lung lobectomy, ischaemia present in the collapsed state is followed by expansion-reperfusion and lung injury attributed to the production of reactive oxygen species. The primary objective of this study was to investigate the time course of several markers of oxidative stress simultaneously in exhaled breath condensate and blood and to determine the relationship between oxidative stress and one-lung ventilation time in patients undergoing lung lobectomy., Methods: This single-centre, observational, prospective study included 28 patients with non-small-cell lung cancer who underwent lung lobectomy. We measured the levels of hydrogen peroxide, 8-iso-PGF2α, nitrites plus nitrates and pH in exhaled breath condensate (n = 25). The levels of 8-iso-PGF2α and nitrites plus nitrates were also measured in blood (n = 28). Blood samples and exhaled breath condensate samples were collected from all patients at five time points: preoperatively; during one-lung ventilation, immediately before resuming two-lung ventilation; immediately after resuming two-lung ventilation; 60 min after resuming two-lung ventilation and 180 min after resuming two-lung ventilation., Results: Both exhaled breath condensate and blood exhibited significant and simultaneous increases in oxidative-stress markers immediately before two-lung ventilation was resumed. However, all these values underwent larger increases immediately after resuming two-lung ventilation. In both exhaled breath condensate and blood, marker levels significantly and directly correlated with the duration of one-lung ventilation immediately before resuming two-lung ventilation and immediately after resuming two-lung ventilation. Although pH significantly decreased in exhaled breath condensate immediately after resuming two-lung ventilation, these pH values were inversely correlated with the duration of one-lung ventilation., Conclusions: During lung lobectomy, the operated lung is collapsed and oxidative injury occurs, with the levels of markers of oxidative stress increasing simultaneously in exhaled breath condensate and blood during one-lung ventilation. These increases were larger after resuming two-lung ventilation. Increases immediately before resuming two-lung ventilation and immediately after resuming two-lung ventilation were directly correlated with the duration of one-lung ventilation., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treatments have some limitations, including parenteral administration (heparins), the need for frequent monitoring and dose adjustments, interactions with several medications, and dietary restrictions (vitamin K antagonists). Rivaroxaban is a new oral direct factor Xa inhibitor with a wide therapeutic window, predictable anticoagulant effect, no food interactions, and few drug interactions. Consequently, no periodic monitoring of anticoagulation is needed, and fixed doses can be prescribed. EINSTEIN program demonstrated that rivaroxaban was as effective as and significantly safer than standard therapy for treatment of VTE. Rivaroxaban was recently authorized so doubts exist about how to use it in daily clinical practice. This document aims to clarify common questions formulated by clinicians regarding the use of this new drug., (© The Author(s) 2014.)

Background: The existence of seasonal variability in patients with acute pulmonary embolism (PE) has been debated for years, with contradictory results. The aim of this study was to identify the trend and possible existence of a seasonal pattern in hospitalizations for PE in Spain., Methods: We analyzed the hospital discharge database of the Spanish National Health System from 2001 to 2010. Patients aged > 14 years diagnosed with PE were selected and a time series was constructed considering mean daily admissions for PE by month. The trend and seasonality factor of the series were determined using time-series analysis, and time-series modeling was used for analysis. Exponential smoothing models and the autoregressive integrated moving average test were used to generate a predictive model., Results: From 2001 to 2010, there were 162,032 diagnoses of PE (5.07 per 1000 hospitalizations). In 105,168 cases, PE was the reason for admission. The PE diagnosis rate ranged from 4.14 per 1000 in 2001 to 6.56 per 1000 in 2010; and hospital admissions due to PE ranged from 2.67 to 4.28 per 1000 hospital discharges. Time-series analysis showed a linear increase in the incidence and a significant seasonal pattern with 17% more admissions in February and 12% fewer in June-July with respect to the central tendency (difference from February to June, 29%)., Conclusions: The incidence of hospitalizations for PE showed a linear increase and a seasonal pattern, with the highest number of admissions in winter and the lowest number in summer., (© 2014 International Society on Thrombosis and Haemostasis.)

The aim of our study was to analyse changes in the incidence, diagnostic procedures, comorbidity, length of hospital stay, costs and in-hospital mortality of patients hospitalised for pulmonary embolism in Spain over a 10-year period. We included all patients who were hospitalised for pulmonary embolism (ICD-9-CM codes 415.11 and 415.19) as the primary diagnosis between 2002 and 2011. Data were collected from the National Hospital Discharge Database, covering the entire Spanish population. 115 671 patients were admitted. The overall crude incidence increased from 20.44 per 100 000 inhabitants in 2002 to 32.69 in 2011 (p<0.05). In 2002, 13.3% of patients had a Charlson comorbidity index>2, and in 2011 the prevalence increased to 20.8% (p<0.05). Mean length of hospital stay was 12.7 days in 2002 and decreased to 9.99 in 2011 (p<0.05). During the study period, mean cost per patient increased from €3915 to €4372 (p<0.05). In-hospital mortality decreased from 12.9% in 2002 to 8.32% in 2011 (p<0.05). The increase in the use of computed tomographic pulmonary angiography over time was associated with increased incidence and lower mortality. Our results revealed an increase in the incidence of hospitalised pulmonary embolism patients from 2002 to 2011 with concomitant increase in comorbidities and cost. However, length of hospital stay and in-hospital mortality decreased., (©ERS 2014.)

Background: Epithelial to mesenchymal transition (EMT) is under discussion as a potential mechanism of small airway remodelling in COPD. In bronchial epithelium of COPD and smokers markers of EMT were described. In vitro, EMT may be reproduced by exposing well-differentiated human bronchial epithelial cells (WD-HBEC) to cigarette smoke extract (CSE). EMT may be mitigated by an increase in cellular cAMP., Objective: This study explored the effects of roflumilast N-oxide, a PDE4 inhibitor on CSE-induced EMT in WD-HBEC and in primary bronchial epithelial cells from smokers and COPD in vitro., Methods: WD-HBEC from normal donors were stimulated with CSE (2.5%) for 72 h in presence of roflumilast N-oxide (2 nM or 1 μM) or vehicle. mRNA and protein of EMT markers αSMA, vimentin, collagen-1, E-cadherin, ZO-1, KRT5 as well as NOX4 were quantified by real-time quantitative PCR or protein array, respectively. Phosphorylated and total ERK1/2 and Smad3 were assessed by protein array. cAMP and TGFβ1 were measured by ELISA. Reactive oxygen species (ROS) were determined by DCF fluorescence, after 30 min CSE (2.5%). Apoptosis was measured with Annexin V/PI labelling. In some experiments, EMT markers were determined in monolayers of bronchial epithelial cells from smokers, COPD versus controls., Results: Roflumilast N-oxide protected from CSE-induced EMT in WD-HBEC. The PDE4 inhibitor reversed both the increase in mesenchymal and the loss in epithelial EMT markers. Roflumilast N-oxide restored the loss in cellular cAMP following CSE, reduced ROS, NOX4 expression, the increase in TGFβ1 release, phospho ERK1/2 and Smad3. The PDE4 inhibitor partly protected from the increment in apoptosis with CSE. Finally the PDE4 inhibitor decreased mesenchymal yet increased epithelial phenotype markers in HBEC of COPD and smokers., Conclusions: Roflumilast N-oxide may mitigate epithelial-mesenchymal transition in bronchial epithelial cells in vitro., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Atypical carcinoids (AC) of the lung are rare intermediate-grade neuroendocrine neoplasms. Prognostic factors for these tumours are undefined., Methods: Our cooperative group retrieved data on 127 patients operated between 1980 and 2009 because of an AC. Several clinical and pathological features were studied., Results: In a univariable analysis, T-status (p=0.005), N-status (p=0.021), preoperative M-status (previously treated) (p=0.04), and distant recurrence developed during the outcome (p<0.001) presented statistically significant differences related to survival of these patients. In a multivariable analysis, only distant recurrence was demonstrated to be an independent risk factor for survival (p<0.001; HR: 13.1). During the monitoring, 25.2% of the patients presented some kind of recurrence. When we studied recurrence factors in a univariable manner, sublobar resections presented significant relationship with locoregional recurrence (p<0.001). In the case of distant recurrence, T and N status presented significant differences. Patients with preoperative M1 status presented higher frequencies of locoregional and distant recurrence (p=0.004 and p<0.001, respectively). In a multivariable analysis, sublobar resection was an independent prognostic factor to predict locoregional recurrence (p=0.002; HR: 18.1)., Conclusions: Complete standard surgical resection with radical lymphadenectomy is essential for AC. Sublobar resections are related to locoregional recurrence, so they should be avoided except for carefully selected patients. Nodal status is an important prognostic factor to predict survival and recurrence. Distant recurrence is related to poor outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: There is scarce evidence to identify which acutely ill medical patients might benefit from prophylaxis against venous thromboembolism (VTE)., Methods: The Spanish National Discharge Database was used to identify predictors of bleeding and VTE during hospitalization for an acute medical illness., Results: Of 1,148,301 patients, 3.10% bled, 1.21% were diagnosed with VTE, and 8.64% died. The case-fatality rate was: 20.8% for bleeding and 19.7% for VTE. Eight clinical variables were independently associated with an increased risk for VTE and bleeding, one with a decreased risk for both events, 4 with an increased risk for VTE and a decreased risk for bleeding, 2 with an increased risk for bleeding but a decreased risk for VTE, and 1 with a decreased risk for bleeding. When all these variables were considered, we composed a risk scoring system, in which we assigned points to each variable according to the ratio between the odds ratio for bleeding and for VTE. Overall, 21% of patients scored less than 0 points and had a bleeding vs. VTE ratio of 1.19; 55% scored 0 to 1.0 points and had a ratio of 2.13; and 24% scored over 1.0 points and had a ratio of 6.10., Conclusions: A risk score based on variables documented at admission can identify patients with different ratios (near 1.0; about 2.0; and >6.0) between the rate of bleeding and of VTE., (© 2013. Published by Elsevier B.V. on behalf of European Federation of Internal Medicine. All rights reserved.)

Background: Angiogenesis and lymphangiogenesis are key mechanisms for tumor growth and dissemination. They are mainly regulated by the vascular endothelial growth factor (VEGF) family of ligands and receptors. The aim of this study was to analyze relative expression levels of angiogenic markers in resectable non-small cell lung cancer patients in order to asses a prognostic signature that could improve characterization of patients with worse clinical outcomes., Methods: RNA was obtained from tumor and normal lung specimens from 175 patients. Quantitative polymerase chain reaction was performed to analyze the relative expression of HIF1A, PlGF, VEGFA, VEGFA165b, VEGFB, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, NRP1 and NRP2., Results: Univariate analysis showed that tumor size and ECOG-PS are prognostic factors for time to progression (TTP) and overall survival (OS). This analysis in the case of angiogenic factors also revealed that PlGF, VEGFA, VEGFB and VEGFD distinguish patients with different outcomes. Taking into account the complex interplay between the different ligands of the VEGF family and to more precisely predict the outcome of the patients, we considered a new analysis combining several VEGF ligands. In order to find independent prognostic variables, we performed a multivariate Cox analysis, which showed that the subgroup of patients with higher relative expression of VEGFA plus lower VEGFB and VEGFD presented the poorest outcome for both TTP and OS., Conclusions: The relative expression of these three genes can be considered as an angiogenic gene signature whose applicability for the selection of candidates for targeted therapies needs to be further validated.

Phytoplankton and its attributes (biomass, abundance, composition, and frequency and intensity of phytoplankton blooms) are essential to establish the ecological status in the Water Frame Directive. The aim of this study is to develop an index "Glophymed" based on all phytoplankton attributes for coastal water bodies according to the directive requirements. It is also developed an anthropogenic pressure index that takes into account population density, tourism, urbanization, industry, agriculture, fisheries and maritime transport for Comunitat Valenciana (Spain). Both indexes (Glophymed and human pressure index) based on a multisampling dataset collected monthly during several years, show a significant statistical correlation (r2 0.75 α<0.01) for typology IIA and (r2 0.93 α<0.01) for typology III-W. The relation between these indexes provides suitable information about the integrated management plans and protection measures of water resources since the Glophymed index is very sensitive to human pressures., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The endothelin (ET) system contributes to lung vascular tension and remodelling in smokers and chronic obstructive pulmonary disease (COPD) patients. This study examined the effect of cigarette smoke (CS) on ET receptor A (ET(A)) and B (ET(B)) expression in human pulmonary artery smooth muscle cells (HPASMCs) and human small intrapulmonary arteries, as well as their functional consequences. CS extract (CSE) increased ET(A) and ET(B) expression in HPASMCs and small intrapulmonary arteries, which was attenuated by bosentan, the ET(A) antagonist BQ123 and the ET(B) antagonist BQ788, and by blocking ET-1 with a monoclonal antibody against ET-1, suggesting a feed-forward mechanism mediated by ET-1 release. ET receptor (ETR) antagonism attenuated the CSE-induced HPASMC proliferation. Furthermore, CSE exposure increased the acute ET-1-induced small intrapulmonary artery contraction, which was attenuated by bosentan, BQ123 and BQ788. Pulmonary arteries from smokers and COPD patients showed a higher expression of ET(A) and ET(B) than those of nonsmoker patients. These results show a novel mechanism by which ETR blockade attenuates CS-induced ETR overexpression and, subsequently, small intrapulmonary artery tension. These data may be of potential value to explain therapeutic effects of bosentan in some forms of disproportionate pulmonary hypertension in COPD patients.

Background: In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC., Materials and Methods: Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m(2) of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m(2) of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m(2) of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate., Results: The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival., Conclusions: Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival.

Background: Qualitative analysis of circulating DNA in the blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of KRAS mutations at codon 12 and several clinical variables in advanced non-small cell lung cancer (NSCLC) patients., Methods: We examined 308 stage IIIB and IV NSCLC patients who were treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. The KRAS mutational status was determined by an RT-PCR method that is based on allelic discrimination., Results: The median age of the patients was 60 years [31-80], 84% were male, 98% had a performance status of 0-1 and 84% of the patients were in stage IV. The histological subtypes were as follows: 30% squamous cell carcinoma (SCC), 51% adenocarcinoma (ADC) and 19% others. Of the 277 response-evaluated patients, 1% achieved a complete response (CR), 26% achieved a partial response (PR), 34% had stable disease (SD) and 39% had progressive disease (PD). Additionally, 27 (8.8%) patients had KRAS mutations; 26 had a KRAS codon 12 TGT mutation, and 1 had a codon 12 GTT mutation. Plasmatic KRAS mutations were found in patients presenting SCC or ADC. Patients with KRAS mutations in plasma DNA had a median progression free survival (PFS) of 5.77 months [3.39-8.14], whereas for patients with wild-type (wt) KRAS, the PFS was 5.43 months [4.65-6.22] (p=0.277). The median overall survival (OS) in KRAS-mutated patients was 9.07 months [4.43-13.70] vs 10.03 months [8.80-11.26] in wt patients (p=0.514)., Conclusions: In advanced NSCLC patients, there were no significant differences between patients with or without KRAS mutations in plasma-free DNA with respect to the baseline characteristics, response rates, PFS or OS., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The impact of venous thromboembolism (VTE) and bleeding in patients undergoing major joint surgery has not been thoroughly studied. The Spanish National Discharge Database during the years 2005-2006 was used to assess the frequency and clinical impact of VTE and bleeding after elective total knee (TKA) or hip (THA) arthroplasty. Of 58,037 patients undergoing TKA, 0.18% (95% confidence interval [CI]: 0.15-0.22) were diagnosed with pulmonary embolism (PE), 0.57% (95% CI: 0.51-0.63) with deep-vein thrombosis (DVT), 1.20% (95% CI: 1.12-1.30) had bleeding complications, and 0.09% (95% CI: 0.07-0.12) died. Of 54 patients who died, 20.4% (95% CI: 10.7-35.4) had been diagnosed with PE, 3.70% (95% CI: 0.63-11.7) with DVT, and 13.0% (95% CI: 5.67-25.6) had bled. Of 31,769 patients undergoing elective THA, 0.23% (95% CI: 0.18-0.29) were diagnosed with PE, 0.44% (95% CI: 0.37-0.52) with DVT, 1.21% (95% CI: 1.10-1.34) bled, and 0.16% (95% CI: 0.12-0.21) died. Of 52 patients who died, 13.5% (95% CI: 6.08-24.8) had been diagnosed with PE, and 9.61% (95% CI: 3.52-21.3) had bled. On multivariable analysis, PE (odds ratio [OR]: 157; 95% CI: 75-328), DVT (OR: 6.3; 95% CI: 1.5-27) and bleeding (OR: 8.5; 95% CI: 3.6-20) were independent predictors for death after TKA. After THA, only PE (OR: 65; 95% CI: 26-160) and bleeding (OR: 6.4; 95% CI: 2.3-17) predicted the risk for death. Bleeding, DVT, and PE, arising after TKA were all independent predictors for death. Their increase in risk was, however, substantially higher for PE. After THA, only PE and bleeding independently predicted death.

Aim: To study the prevalence of hypertriglyceridemic waist (HTGW) in an urban adult Spanish population and its association with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD)., Methods: We undertook a cross-sectional analysis in a random sample of 2270 individuals (18-80 years of age). All participants provided a clinical history and underwent a physical examination. Blood and urine analyses were conducted. HTGW was diagnosed using anthropometric criteria for the European population (waist circumference: for men, ≥ 94 cm; for women, ≥ 80 cm) and fasting plasma triglycerides (TGs) ≥ 1.71 mmol l(-1) (≥ 150 mg per 100 ml)., Results: The prevalence of HTGW was 14.5% (men: 18.2%, women: 10.8%) and was significantly greater in men <59 years (P<0.001). HTGW was associated with older individuals, a low educational level and, in men, with a sedentary lifestyle (P<0.001). Subjects with HTGW had higher levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-c) and uric acid, lower levels of high-density lipoprotein-cholesterol, a higher blood pressure, a greater degree of obesity and a higher prevalence of T2DM (20.00 vs 6.4%, P<0.001) (odds ratio (OR) 3.61; 95% confidence interval (95% CI), 2.60-5.01) and CVD (8.5 vs 3.4%, P<0.001) (OR 2.63; 95% CI, 1.66-4.16). The association of HTGW with T2DM and CVD disappeared after adjusting for age. The degree of concordance between HTGW and the metabolic syndrome (MS) was moderate, with both the Adult Treatment Panel III Report (ATP-III) and the International Diabetes Federation criteria (κ=0.51 and κ=0.58, respectively). Subjects with isolated HTGW as compared with those with isolated MS (ATP-III) were younger, had greater levels of total cholesterol, LDL-c and TGs and a lower prevalence of obesity, high blood pressure and dysglycemia., Conclusion: HTGW is a phenotype of cardiometabolic risk prevalent in the adult population in our environment. HTGW may be an alternative to MS to detect the population at risk for T2DM and CVD, especially in young individuals who do not fulfill the criteria for MS.

Introduction: The aim of this study was to investigate the effectiveness of thoracoscopy in the diagnosis of non-affiliated pleural effusions (PE)., Material and Methods: A five-year prospective study including data from 110 patients that were clinically diagnosed as benign (14.5%), malign (34.5%) and non-affiliated (50.9%). PE in patents without oncology disease and negative biopsy or cytology were considered as benign. Malignant diagnosis was established according to a pleural biopsy, compatible cytology and/or clinical features. Remaining cases were considered as non-affiliated. Thoracoscopy was done under local anaesthesia and sedation., Results: Thoracoscopy confirmed previous clinical diagnosis of benignity and malignity. Regarding non-affiliated patients, 30.35% were diagnosed after thoracoscopy as unspecific pleuritis, 17.86% mesothelioma and 1.79% pleural tuberculosis (TBC). The other 48.21% of patients reported as non-affiliated were diagnosed with pleural carcinoma. Statistical analysis did not reveal differences between frequencies analysed., Conclusions: Our results indicate that thoracoscopy is a cost-effective and reliable technique for obtaining histological diagnosis in PE and also allows a directed pleurodesis if indicated.

The doctor-patient relationship has undergone important changes in recent years. Increasing levels of distrust on the part of patients toward professionals and institutions have led to an increase in the number of conflicts that end in violent actions against health service personnel. The aim of this study is to analyse this phenomenon in the public welfare services of the Region of Murcia (Spain), based on an analysis of accusations presented by doctors in the courts between 2006 and April 2008. The conclusion reached in this study can presumably be extrapolated to the rest of Spain. The violent reactions in question resulted from patients demanding drug prescriptions, the prolongation of sick leave and the demand for diagnostic tests. The Public Health Services provide directives for the anticipation of and abstention from such situations, emphasize the training of professionals in communication skills, the promotion of skills of negotiation and emotional self-control. Other measures include the installation of alarms, intercoms and video cameras, contracting security companies, collaboration with the police and posters in health facilities warning that legal action will be taken. Nevertheless, given the obvious inadequacy of the above mentioned measures Plans of Prevention have been put in place. In addition legal defence has been granted to all such professionals. From a judicial point of view, these aggressions are judged as minor crimes of injury or insult. The most recent view taken on such conduct is to consider it as a crime of attempt or an offence against the authority, which has been confirmed in law by the recent judgment passed down by the Spanish High Court on 4th December, 2007.

Background: The purpose of this study was to analyze and determine the prevalence and clinical characteristics of hospitalized dementia patients compared with nondemented patients., Methods: We examined hospital discharge database records dated 1998-2003 from public hospitals in Andalusia, Spain. We used ICD-9-CM codes to identify patients with dementia. The variables examined included age, length of stay, discharge diagnosis, diagnostic-related groups, and mortality of both dementia and nondementia patients over 65 years of age., Results: A diagnosis of dementia was documented for 40,482 cases. The prevalence of dementia increased from 3.43% to 4.64% between 1998 and 2003 and was higher among older patients and women. Dementia was the reason for admission in 5.6% of cases. Medical reasons constituted 82.4% of admittances. Dementia patients had hip surgery more frequently than patients without dementia, and other procedures (orthopedic surgery, cataracts, or hernia repair) were less frequent (p < 0.001). The mean duration of the hospital stay was longer (13.4 vs. 10.7 days) and the intra-hospital mortality rate was greater (19.3% vs. 8.7%) for patients with dementia compared to those without dementia. Dementia was an independent predictor of mortality (OR 1.77; 95% CI 1.72-1.82)., Conclusions: Dementia is increasing among hospitalized patients. Dementia patients have different reasons for hospitalization and higher mortality. It is necessary to identify these differences and to improve the hospital care of dementia patients., (Copyright 2010 S. Karger AG, Basel.)

Purpose: To address whether preoperative chemotherapy plus surgery or surgery plus adjuvant chemotherapy prolongs disease-free survival compared with surgery alone among patients with resectable non-small-cell lung cancer., Patients and Methods: In this phase III trial, 624 patients with stage IA (tumor size > 2 cm), IB, II, or T3N1 were randomly assigned to surgery alone (212 patients), three cycles of preoperative paclitaxel-carboplatin followed by surgery (201 patients), or surgery followed by three cycles of adjuvant paclitaxel-carboplatin (211 patients). The primary end point was disease-free survival., Results: In the preoperative arm, 97% of patients started the planned chemotherapy, and radiologic response rate was 53.3%. In the adjuvant arm, 66.2% started the planned chemotherapy. Ninety-four percent of patients underwent surgery; surgical procedures and postoperative mortality were similar across the three arms. Patients in the preoperative arm had a nonsignificant trend toward longer disease-free survival than those assigned to surgery alone (5-year disease-free survival 38.3% v 34.1%; hazard ratio [HR] for progression or death, 0.92; P = .176). Five-year disease-free survival rates were 36.6% in the adjuvant arm versus 34.1% in the surgery arm (HR 0.96; P = .74)., Conclusion: In early-stage patients, no statistically significant differences in disease-free survival were found with the addition of preoperative or adjuvant chemotherapy to surgery. In this trial, in which the treatment decision was made before surgery, more patients were able to receive preoperative than adjuvant treatment.

It is considered that up to 20% of the craniosinostosis patients require secondary surgeries. Different techniques have been used in craneofacial surgery for the reconstruction of great osseous defects in pediatric patients for many years. This paper is about a new technique to obtain osseous graft for covering osseous cranial defects, using particulate bone, harvested from the patient calvarian using a hand-driven brace and covered with a fibrin adhesive. This is a very simple technique, which provides a great amount of bone from the patient himself, therefore producing a small morbidity. Since 2007 the authors have been using autologous particulate bone harvested from de patient calvarian for the reconstruction of different size osseous defects found in craneofacial surgery, especially in pediatrics patients. Although alloplastic materials and bone substitutes have been used for cranial reconstruction, the best option is the autogenous bone. In contrast to synthetic materials autologous grafts have a faster osteointegration, due to their osteogenic, osteoinductive and osteconductive properties. Harvesting the bone from the calvarian patient produces a minimal morbidity compared to the extraction of grafts from other donor sites such as rips or hip. The use of autologous particulate bone in craniosinostosis surgery reduces the risk of second interventions due to secondary ossifications defects. On the other hand, the harvest is easy and the supply of bone it is enough in pediatric patients.

Cigarette smoke mediated oxidative stress and endothelial dysfunction are important processes in the pathogenesis of several lung disorders. In this study we evaluated the effect of PDE5 inhibition on pulmonary artery endothelial dysfunction induced by cigarette smoke in vitro. Human pulmonary artery endothelial cells (HPAEC) were incubated in the absence or presence of PDE5 inhibitor sildenafil (10 nM-1 microM), PKG agonist 8-Br-cGMP (1mM), or the antioxidants dyphenyleneiodonium (DPI 1 microM) and N-acetylcysteine (NAC 1mM) for 30 min. Then, cigarette smoke extract (CSE) was added for 24h. CSE (2.5-10%)-induced ROS generation was suppressed by DPI, and partially reversed by sildenafil and 8-Br-cGMP. Decreases in intracellular levels of cGMP and extracellular NO induced by CSE were reversed by sildenafil and DPI. Furthermore, CSE-induced pg91(phox) and PDE5 mRNA overexpression were suppressed by both sildenafil and DPI. CSE (2.5-10%) induced upregulation of IL-6, IL-8 and Ang-2, and decreased Ang-1 expression in parallel to apoptosis which were partially suppressed by sildenafil, 8-Br-cGMP, DPI and NAC. This study demonstrates that PDE5 inhibition attenuates the oxidant burden and the inflammatory and remodeling effects of CSE in human HPAEC which may contribute to the therapeutic value of PDE5 inhibitors for pulmonary disorders coursing with endothelial dysfunction., (Copyright 2010 Elsevier B.V. All rights reserved.)

The doctor-patient relationship has undergone important changes in recent years. Increasing levels of distrust, on the part of patients towards professionals and institutions, have led to an increase of conflicts resulting in violent actions against health service personnel. The aim of this study is to analyse this phenomenon in the public welfare services of the Region of Murcia (Spain), based on an analysis of accusations, as were presented by doctors in courts in the period between 2006 and April 2008. The conclusion reached can presumably be extrapolated to the rest of Spain. The violent reactions in question resulted from patients demanding drug prescriptions; the prolongation of sick leave and the demand for diagnostic tests. The Public Health Services provide directives to anticipate and avoid such situations, emphasize the training of professionals in communication skills, the promotion of skills of negotiation and emotional self-control. Other measures include the installation of alarms, intercoms and video cameras, contracting security companies, collaboration with the police and posters in health facilities warning that legal action will be taken. Nevertheless, given the obvious inadequacy of the above-mentioned measures, Plans of Prevention have been put in place. In addition legal defence has been granted to all such professionals. From the judicial point of view, these aggressions are judged as minor crimes of injury, insult and threat. The most recent view taken on such conduct is to consider it as a crime of attempt or offence against the authority, which has been confirmed in law by the recent judgment passed down by the Spanish High Court on 4th December, 2007.