Soluble galectin-3 as a microenvironment-relevant immunoregulator with prognostic and predictive value in lung adenocarcinoma.

Despite the success of therapies in lung cancer, more studies of new biomarkers for patient selection are urgently needed. The present study aims to analyze the role of galectin-3 (GAL-3) in the lung tumor microenvironment (TME) using tumorspheres as a model and explore its potential role as a predictive and prognostic biomarker in non-small cell lung cancer patients. For in vitro studies, lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) primary cultures from early-stage patients and commercial cell lines were cultured, using tumorsphere-forming assays and adherent conditions for the control counterparts. We analyzed the pattern of secretion and expression of GAL-3 using reverse transcription-quantitative real-time PCR (RTqPCR), immunoblot, immunofluorescence, flow cytometry, and immunoassay analysis. Our results using three-dimensional (3D) models of lung tumor cells revealed that soluble GAL-3 (sGAL-3) is highly expressed and secreted. To more accurately mimic the TME, a co-culture of tumorspheres and fibroblasts was used, revealing that GAL-3 could be important as an immunomodulatory molecule expressed and secreted in the TME, modulating immunosuppression through regulatory T cells (TREGS ). In the translational phase, we confirmed that patients with high expression levels of GAL-3 had more TREGS , which suggests that tumors may be recruiting this population through GAL-3. Next, we evaluated levels of sGAL-3 before surgery in LUAD and LUSC patients, hypothesizing that sGAL-3 could be used as an independent prognostic biomarker for overall survival and relapse-free survival in early-stage LUAD patients. Additionally, levels of sGAL-3 at pretreatment and first response assessment from plasma to predict clinical outcomes in advanced LUAD and LUSC patients treated with first-line pembrolizumab were evaluated, further supporting that sGAL-3 has a high efficiency in predicting durable clinical response to pembrolizumab with an area under curve of 0.801 (P = 0.011). Moreover, high levels might predict decreased progression-free survival and OS to anti-PD-1 therapy, with sGAL-3 being a prognosis-independent biomarker for advanced LUAD.

A new mixed reality tool for training in minimally invasive robotic-assisted surgery.

Robotic-assisted surgery (RAS) is developing an increasing role in surgical practice. Therefore, it is of the utmost importance to introduce this paradigm into surgical training programs. However, the steep learning curve of RAS remains a problem that hinders the development and widespread use of this surgical paradigm. For this reason, it is important to be able to train surgeons in the use of RAS procedures. RAS involves distinctive features that makes its learning different to other minimally invasive surgical procedures. One of these features is that the surgeons operate using a stereoscopic console. Therefore, it is necessary to perform RAS training stereoscopically. This article presents a mixed-reality (MR) tool for the stereoscopic visualization, annotation and collaborative display of RAS surgical procedures. The tool is an MR application because it can display real stereoscopic content and augment it with virtual elements (annotations) properly registered in 3D and tracked over time. This new tool allows the registration of surgical procedures, teachers (experts) and students (trainees), so that the teacher can share a set of videos with their students, annotate them with virtual information and use a shared virtual pointer with the students. The students can visualize the videos within a web environment using their personal mobile phones or a desktop stereo system. The use of the tool has been assessed by a group of 15 surgeons during a robotic-surgery master's course. The results show that surgeons consider that this tool can be very useful in RAS training.

A Sonic Hedgehog Pathway Score to Predict the Outcome of Resected Non-Small Cell Lung Cancer Patients.

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.

Intubation with vivasight double-lumen tube versus conventional double-lumen tube in adult patients undergoing lung resection: A retrospective analysis.

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.

A new strategy in lung/lobe isolation in patients with a lung abscess or a previous lung resection using double lumen tubes combined with bronchial blockers.

The combined use of a double-lumen tube and a bronchial blocker can be very helpful in two different clinical scenarios: (1) in isolating not only the contralateral lung, but also the lobe/s of the same lung in which the infected lobe must be resected, (2) in preventing/treating hypoxemia because of the presence of a contralateral lobectomy. A cardiothoracic anesthesiologist must expertise this technique to avoid complications during surgery.

Analysis of Exosomal Cargo Provides Accurate Clinical, Histologic and Mutational Information in Non-Small Cell Lung Cancer.

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.

Characterization of Circulating T Cell Receptor Repertoire Provides Information about Clinical Outcome after PD-1 Blockade in Advanced Non-Small Cell Lung Cancer Patients.

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-ß) 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-ß 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-ß 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.

Clinicopathological significance of the expression of PD-L1 in non-small cell lung cancer.

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.

Lung tumorspheres reveal cancer stem cell-like properties and a score with prognostic impact in resected non-small-cell lung cancer.

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.

Surgical treatment of low and intermediate grade lung net.

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 7th 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.

MicroRNA profiling associated with non-small cell lung cancer: next generation sequencing detection, experimental validation, and prognostic value.

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-21high and miR-188high) 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.

Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial.

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.

Analysis of the prognostic role of an immune checkpoint score in resected non-small cell lung cancer patients.

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.

Type 2 diabetes is associated with a higher incidence of hospitalization for pulmonary embolism in Spain: Analysis of hospital discharge data during 2004-2013.

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.

Analysis of the immune microenvironment in resected non-small cell lung cancer: the prognostic value of different T lymphocyte markers.

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.

Trends in the Management and Outcomes of Acute Pulmonary Embolism: Analysis From the RIETE Registry.

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.

Glutathione oxidation correlates with one-lung ventilation time and PO2/FiO2 ratio during pulmonary lobectomy.

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.

Pulmonary embolism, acute coronary syndrome and ischemic stroke in the Spanish National Discharge Database.

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.