Search

Precise predictions are provided for the production of a Z boson and a b-jet in hadron-hadron collisions within the framework of perturbative QCD, at O(α_{s}^{3}). To obtain these predictions, we perform the first calculation of a hadronic scattering process involving the direct production of a flavored jet at next-to-next-to-leading-order accuracy in massless QCD and extend techniques to also account for the impact of finite heavy-quark mass effects. The predictions are compared to CMS data obtained in pp collisions at a center-of-mass energy of 8 TeV, which are the most precise data from run I of the LHC for this process, where a good description of the data is achieved. To allow this comparison, we have performed an unfolding of the data, which overcomes the long-standing issue that the experimental and theoretical definitions of jet flavor are incompatible.

Background: In the US, carfilzomib 70 mg⁄m 2 once-weekly plus dexamethasone (Kd70 QW) was recently indicated for relapsed and/or refractory multiple myeloma. In current US clinical practice, most patients treated with Kd receive carfilzomib at a previously approved dose of 27 mg/m 2 twice-weekly (Kd27 BIW). This analysis assessed the cost-effectiveness (CE) of Kd70 QW vs Kd27 BIW regimens which were compared in the randomized phase 3 ARROW trial., Methods: Based on clinical outcomes (overall survival and utilities) from ARROW, a partitioned survival model was developed to estimate life years (LYs) and quality-adjusted life years (QALYs). Long-term survival was extrapolated using SEER registry data matched to ARROW patients. Costs were estimated using a US healthcare payer perspective., Results: The analysis estimated that treatment with Kd70 QW vs Kd27 BIW resulted in an increase of 1.10 LYs, 0.91 QALYs, and additional lifetime costs of $74,858, yielding an incremental CE ratio (ratio of incremental costs to QALYs) of $82,257 per QALY gained. Results were robust to sensitivity and subgroup analyses., Conclusions: When compared with Kd27 BIW, Kd70 QW is the optimal dose that represents a cost-effective utilization of health care budget with incremental CE ratios well below the accepted willingness-to-pay thresholds in the US.

Background: Sarcoidosis and hypersensitivity pneumonitis (HP) are immunologically mediated processes caused by hypersensitivity reaction accompanied by similar features including lymphocytic alveolitis and granuloma formation. Recent studies describe the role of TREM receptors in T cell activation, differentiation, and granuloma formation. Alveolar macrophages activation via TREM receptors may be the key factor mediating subsequent immune response. The aim of the study was to analyse TREM-1 and TREM-2 expression to identify further molecular mechanisms participating in the immunopathogenesis of sarcoidosis and HP., Methods: Flow cytometry was performed to analyse TREM-1 and TREM-2 expression on CD14 + cells in bronchoalveolar lavage fluid from patients having sarcoidosis or HP and a control group., Results: The study proved increased TREM-1 expression on alveolar macrophages in pulmonary sarcoidosis and diminished TREM-1 expression in HP-Sarcoidosis: median: 76.7; HP: median: 29.9; control: median: 53.3, (sarcoidosis versus HP: p < 0.001; sarcoidosis versus control: p < 0.05). TREM-2 expression was increased in both, sarcoidosis and HP-sarcoidosis: median: 34.79; HP: median: 36.00; control: median: 12.98, (sarcoidosis versus control: p < 0.05; HP versus control: p < 0.05). Correlation analysis showed negative correlation between TREM-1 and total number of CD8 + cytotoxic T cells. In sarcoidosis TREM-1 expression decreased with changes of HRCT image, decrease in CD4/CD8 ratio and decrease in DLCO., Conclusions: Differences in TREM receptor expression in sarcoidosis (increase in TREM-1 and TREM-2) and HP (increase in TREM-2) and correlation analysis suggests that activation via TREM may participate in typical immunological characteristics of sarcoidosis and HP., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 M. Suchankova et al.)

Disclosures: No funding was involved in the writing of this letter. Medhekar, Sapra, Majer, Harrison, and Tekle are employees of and stockholders in Amgen.

Objectives: Analysis of new markers in bronchoalveolar lavage fluid (BALF) provides new insights into the immunopathogenesis and may be helpful in differential diagnosis of lung diseases. High mobility group box 1 protein (HMGB1) is a non-histone nuclear protein and its release into the extracellular environment may be associated with the inflammatory response. The aim of the study is the analysis of HMGB1 in BALF, correlations with other markers of inflammation and differences in extracellular HMGB1 levels in various lung diagnoses. Methods: The concentration of HMGB1 was tested by an Elisa test. We calculated correlations with other inflammatory markers (leukocytes, total protein, albumin, IgG, IgA, IgM, C3 complement component, alpha-2macroglobuline, CD3, CD4, CD8, TREM-1 and TREM-2) and specified HMGB1 level in various diagnoses. Results: A positive correlation was found between the level of HMGB1 and total protein levels (p=0.0001), albumin (p=0.0058), IgA (p=0.011), IgM (0.0439) and TREM-2 (p=0.0188). Conversely, a negative correlation was revealed between HMGB1 and TREM-1 (p=0.0009). HMGB1 level varied in different diagnoses: the highest level was detected in QuantiFERON TB-positive subjects (median: 30.2) and hypersensitivity pneumonitis (median: 33.2), followed by pulmonary sarcoidosis (median: 16.8) and idiopathic pulmonary fibrosis (median: 8.8). Conclusion: HMGB1 correlates with other inflammatory markers tested in BALF. Its level varies in different lung diagnoses. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 268-275) ., (Copyright: © 2018.)

Background: Respiratory syncytial virus (RSV) infection remains one of the major reasons of re-hospitalization among children with congenital heart disease (CHD). This study estimated the cost-effectiveness of palivizumab prophylaxis versus placebo, in Spain, from the societal perspective, using a novel cost-effectiveness model reflecting evidence-based clinical pathways., Methods: A decision-analytic model, combining a decision tree structure in the first year and a Markov structure in later years, was constructed to evaluate the benefits and costs associated with palivizumab versus no prophylaxis among children with CHD. In the first year of the model, children were at risk of mild (i.e. medically attended, MA-RSV) and severe (hospitalized, RSV-H) RSV infection. The impact of delayed corrective CHD surgery due to RSV infection and the consequence of performed surgery despite severe infection were considered. In later years, patients were at risk of developing asthma and allergic sensitization as sequelae of RSV infection. Input data for the model were derived from the pivotal clinical trial and systematic literature reviews. Indirect costs included parental absence from work and nosocomial infections. In agreement with Spanish guidelines, costs and effects were discounted at 3%., Results: Over a lifetime horizon, palivizumab prophylaxis yielded 0.11 and 0.07 additional quality-adjusted life years (QALYs) and life years (LYs), respectively, at additional costs of € 1,693, resulting in an ICER of € 15,748 per QALY gained and € 24,936 per LY gained. Probabilistic sensitivity analyses demonstrated that the probability of palivizumab prophylaxis being cost-effective at a € 30,000 per QALY threshold was 92.7%. The ICER remained below this threshold for most extreme scenario analyses., Conclusions: The model demonstrated that palivizumab prophylaxis results in more QALYs than no prophylaxis in children with CHD. Palivizumab prophylaxis was shown to be a cost-effective health care intervention according to the commonly accepted standards of cost-effectiveness in Spain (ICER below the threshold of € 30,000 per QALY).

Background: Since persistence to first biological disease modifying anti-rheumatic drugs (bDMARDs) is far from ideal in rheumatoid arthritis (RA) patients, many do receive a second and/or third bDMARD treatment. However, little is known about treatment persistence of the second-line bDMARD and it is specifically unknown whether the mode of action of such a treatment is associated with different persistence rates. We aimed to assess discontinuation-, re-initiation- or continuation-rates of a 2nd bDMARD therapy as well as switching-rates to a third biological DMARD (3rd bDMARD) therapy in RA patients., Method: Analysis was based on German claims data (2010-2013). Patients were included if they had received at least one prescription for an anti-TNF and at least one follow-up prescription of a 2nd bDMARD different from the first anti-TNF. Patient follow-up started on the date of the first prescription for the 2nd bDMARD and lasted for 12 months or until a patient's death., Results: 2667 RA patients received at least one anti-TNF prescription. Of these, 451 patients received a second bDMARD (340 anti-TNF, mean age 52.6 years; 111 non-anti-TNF, mean age 55.9 years). During the follow-up, 28.8% vs. 11.7% of the 2nd anti-TNF vs. non-anti-TNF patients (p < 0.001) switched to a 3rd bDMARD; 14.1% vs. 19.8% (p = 0.179) discontinued without re-start; 3.8% vs.1.8% (p = 0.387) re-started and 53.5 vs. 66.7% (p < 0.050) continued therapy. Patients in the non-anti-TNF group demonstrated longer drug survival (295 days) than patients in the anti-TNF group (264 days; p = 0.016). Independent variables associated with earlier discontinuation (including re-start) or switch were prescription of an anti-TNF as 2nd bDMARD (HR = 1.512) and a higher comorbidity level (CCI, HR = 1.112), whereas previous painkiller medication (HR = 0.629) was associated with later discontinuation or switch., Conclusions: Only 56.8% of RA patients continued 2nd bDMARD treatment after 12 months; 60% if re-start was included. Non-anti-TNF patients had a higher probability of continuing 2nd bDMARD therapy.

Background: In the UK, the standard of care for patients with multiple myeloma who received ≥2 prior treatments is lenalidomide plus dexamethasone (LEN + DEX) and pomalidomide plus DEX (POM + DEX) (in Wales only). Recently, panobinostat plus bortezomib and DEX (PAN + BTZ + DEX) was licensed in this setting. The current study assessed the progression-free survival (PFS) and overall survival (OS) outcomes with PAN + BTZ + DEX versus LEN + DEX (primary comparator) and POM + DEX (exploratory comparator)., Methods: Since an anchor-based indirect treatment comparison was not feasible, the matching-adjusted indirect treatment comparison approach was used. To compare the survival outcomes, patient-level data were generated for the comparators utilizing published Kaplan-Meier survival estimates. The use of approximated patient-level data and matched data for PAN + BTZ + DEX allowed the use of Cox proportional hazards models and the assessment of the proportional hazards assumption. In cases where there was evidence that the proportional hazards assumption was violated, time-dependent hazard ratios (HRs) were estimated. Median and mean values for PFS and OS were predicted., Results: For both PFS and OS, the proportional hazards assumption was not satisfied, therefore time-dependent HRs were estimated. Using time-dependent HRs, the mean PFS was estimated to be 11.83 months for PAN + BTZ + DEX and 10.96 months for LEN + DEX. The corresponding mean OS estimates were 30.73 and 27.76 months, respectively. Comparisons with POM + DEX were affected by large uncertainty and did not allow making robust inferences., Conclusions: To our knowledge, this is the first study that combined matching-adjusted indirect treatment comparison with time-dependent HRs to address changing patterns in the HR. The results suggest that treatment with PAN + BTZ + DEX and LEN + DEX are associated with similar mean PFS and OS in the third-line treatment setting of multiple myeloma.

The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA ( Contre les Maladies Chroniques pour un Vieillissement Actif )-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

Non-small cell lung cancer (NSCLC) is a histologically and molecularly heterogeneous disease predominating in Slovakia among newly diagnosed oncological disorders and leading in the number of associated deaths. NSCLC diagnostics has advanced especially in molecular typing of epidermal growth factor receptor (EGFR) and subsequent targeted molecular therapy using tyrosine-kinase inhibitor(s) (TKI). The selection of patients for targeted therapy, we describe in this study, is mostly guided through bronchial smears rather than more invasive biopsies. We identified 32 adenocarcinomas, 40 squamous-cell carcinomas, 12 large-cell carcinomas, along with two unspecified carcinomas, in the NSCLC group who had bronchial smears taken. The assessment of tumor cell number, and genomic DNA allowed for screening of clinically relevant somatic EGFR mutations in 86 patients. Using quantitative PCR, 12 patients (14 %) were recommended for EGFR-TKI therapy. The most prevalent EGFR HIT-a in the somatosome, terms introduced and defined in this study, were exon 19 deletions, which were found in combination with the TKI-resistant p.T790M mutation in exon 20 in one patient. The study describes a method that is minimally invasive, reliable, and meets all criteria of routine molecular diagnostics. A multidisciplinary approach of EGFR genotyping from bronchial smears implemented in the study allows expanding targeted molecular therapy in NSCLC patients.

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This retrospective medical chart review aimed to provide a current, real-world overview of biologic usage in patients with rheumatoid arthritis (RA) in Germany, Spain, and the UK, and estimate clinical and healthcare utilization outcomes associated with early versus late treatment. Adults (≥18 years) with a confirmed RA diagnosis between January 2008 and December 2010, who received biologic treatment for ≥3 months and had ≥12 months of follow-up were included. Early treatment was receipt of biologic agent ≤1 year after RA diagnosis. Outcomes included 28-joint disease activity score (DAS28) reduction of ≥1.2 from biologic start and remission (DAS28 < 2.6). Time to outcome was evaluated using Kaplan-Meier curves and log-rank tests. Of 328 patients enrolled (Germany [n = 111], Spain [n = 106], UK [n = 111]), 58.2 % received early biologic (Germany: 55.0 %, UK: 55.9 %, Spain: 64.2 %; p = 0.321). First-line biologics were more frequent in Spain (26.4 %) and Germany (19.8 %) versus the UK (7.2 %; p < 0.001). Late-treated patients were hospitalized more often than early-treated patients (10.5 vs 2.9 % [p = 0.006] for 9.0 vs 5.4 mean inpatient days [p = 0.408]). DAS28 was 5.1 at biologic initiation (n = 310); 73.5 % of patients had a DAS28 decrease of ≥1.2 and 44.5 % achieved remission. More patients had DAS28 decrease of ≥1.2 (79.2 vs 65.9 %; p = 0.009) and remission (51.1 vs 35.6 %; p = 0.007) with early versus late treatment, with a significant difference in Kaplan-Meier curves when indexing on time since diagnosis (p < 0.001) and biologic start (p = 0.024). In RA patients receiving biologic therapy, over half received biologic therapy early. Early initiation was associated with improved clinical outcomes and reduced hospitalization rates versus late treatment.

The recent studies suggest a role of fungi in development of sarcoidosis. Moreover, the immune response in sarcoidosis and fungal infection shows a striking similarity. We formulated a hypothesis of the possible increase in antifungal antibodies in bronchoalveolar lavage fluid (BALF) and serum in pulmonary sarcoidosis. BALF and serum levels of IgG-, IgM- and IgA-specific antibodies against the cell wall β-D-glucan and mannan of Candida albicans and Saccharomyces cerevisiae were tested in 47 patients (29 pulmonary sarcoidosis patients and 18 patients with other interstitial lung diseases (ILD - control group)) and 170 healthy controls. Our results proved: (1) an increase in IgG-, IgM- and IgA-specific antifungal antibodies in BALF in pulmonary sarcoidosis compared with the control group (C. albicans: IgG: P = 0.0329, IgM: P = 0.0076, IgA: P = 0.0156; S. cerevisiae: IgG: P = 0.0062, IgM: P = 0.0367, IgA: P = 0.0095) and (2) elevated levels of serum antifungal antibodies in pulmonary sarcoidosis compared with healthy controls (C. albicans: IgG: P = 0.0329, IgM: P = 0.0076, IgA: P = 0.0156; S. cerevisiae: IgG: P > 0.05, IgM: P < 0.05, IgA: P < 0.001). The study showed increased serum and BALF levels of antifungal antibodies in pulmonary sarcoidosis. The hypothesis that fungal infection is one of the possible aetiologic agents of sarcoidosis is interesting and deserves further attention., (© 2015 John Wiley & Sons Ltd.)

TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels.

Background: Triggering receptors expressed on myelocytes (TREM) belong to new molecules with a great role in innate immune system and inflammation. While TREM-1 is known for its pro-inflammatory activity, the TREM-2 has anti-inflammatory activity and has a great impact on granuloma formation, typical sign of sarcoidosis and other granulomatous diseases., Methods: In our study, we compared the TREM-1 and TREM-2 receptor expressions on the myeloid cell surfaces in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis (PS), other interstitial lung diseases (ILD), asthma bronchiale (AB), pneumonia, lung cancers, and Quantiferon TB positive patients., Results: We found increased number of all TREM variables (total number, percentage, and mean fluorescence intensity /MFI/) of TREM-1 and TREM-2 positive cells in PS and AB patients compared to the control group of patients with other ILD. In patients with pneumonia, only expression of TREM-1 receptor was increased. In ILD, AB and group of pneumonia patients, the increase of TREM-1 and TREM-2 expression was associated with an increased number of eosinophils., Conclusion: TREM-1 and TREM-2 tests are good diagnostic tests for sarcoidosis. Their sensitivity and specificity are comparable with the currently common using test, that of CD4/CD8 ratio. The combination of both tests (CD4/CD8 ratio test together with TREM-1 and TREM-2 tests) resulted in an increased sensitivity and specificity (Tab. 7, Fig. 1, Ref. 28).

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

Mutation analysis of the epidermal growth factor receptor (EGFR) gene is an essential part of the diagnostic algorithm in patients with metastatic or recurrent non-small cell lung cancer (NSCLC). Small biopsies or cytology specimens represent >80% of the available diagnostic material. EGFR mutation analyses were realized on 835 samples (675 cytology specimens, 151 formalin-fixed paraffin-embedded blocks, 5 tumors, and 4 pleural effusions). EGFR mutation analysis was performed by high-resolution melting analysis in combination with mutant-enriched polymerase chain reaction and sequencing analysis. Because of increased risk of inaccuracy in histology diagnosis of small specimens, all subtypes of NSCLC were analyzed. EGFR mutations were detected in 83 cases (10%). EGFR mutation testing failed in 5% (42/835) and was associated with poor cellularity, low percentage of tumor cells, and bad quality of DNA. Although 281 samples were evaluated as insufficient material (poor cellularity and/or unrepresentative tumor content), mutation rates were 7%. Although only adenocarcinomas or NSCLC-not otherwise specified are recommended for EGFR mutation testing, EGFR mutations in 11% of the large cell carcinomas and 4% of the squamous cell carcinomas were observed. Our results indicate that defined algorithm for EGFR testing of small diagnostic samples is sensitive, fast, and suitable even for samples with poor cellularity. The results of this testing should be evaluated depending on tumor content and DNA quality for each sample individually. At the conclusion of our results, we recommend to realize EGFR mutation analysis of small diagnostic samples regardless of the histologic subtypes of NSCLC.

Background and Objective: Pulmonary sarcoidosis (PS) is characterized by the formation of granulomas in the lungs and has been associated with infection by microorganisms. Triggering receptor expressed on the surface of myeloid cells (TREM)-1 is overexpressed in response to infection while TREM-2 is involved in granuloma formation. We hypothesized that these receptors are overexpressed in PS and might be useful for diagnostic testing., Methods: Cell surface TREM-1 and TREM-2 expression in cells obtained at bronchoalveolar lavage (BAL) was measured in individuals with sarcoidosis (n = 26) and compared with that seen in individuals with other interstitial lung diseases (ILD) (n = 27)., Results: TREM-1 and TREM-2 expression was significantly increased in sarcoidosis compared with other ILD: total number of TREM-1, P = 0.0039 (23.81 vs 13.50 cells/μl), TREM-2, P < 0.0001 (32.81 vs 7.76 cells/μl); percentage of TREM-1: P = 0.0002 (41.30% vs 15.70%), TREM-2: P < 0.0001 (34% vs 9.60%); and mean fluorescence of TREM-1: P = 0.0005 (5.43 vs 1.96), TREM-2: P = 0.0011 (6.85 vs 2.77). Increase in both of these receptors seems to be typical for PS. In discriminating sarcoidosis from other ILD, the specificity (96%) and sensitivity (72%) of the combination of TREM-1 and TREM-2 was high., Conclusions: Increased TREM-1 and TREM-2 cell surface expression is observed in sarcoidosis. Evaluation of BAL cell expression of both of these receptors may serve as a diagnostic marker for sarcoidosis., (© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.)

Soluble TREM-1 (sTREM-1; Triggering receptor expressed on myelocytes) is a new inflammatory marker indicating the intensity of myeloid cells activation and the presence of infection caused by extracellular bacteria and mould.The aim of our work was to detect and compare the levels of sTREM-1 in bronchoalveolar lavage fluid (BALF) in patients with pulmonary sarcoidosis (PS) and other ILD of non-infectious origin. The sTREM-1 levels were assessed by ELISA in 46 patients suffering from ILD, out of them 22 with PS. The levels of BALF sTREM-1 in PS patients were higher than in control group of ILD patients of non-infectious origin, however, the difference was not statistically significant. Since all PS patients except one were non-smokers we compared non-smokers PS with non-smokers ILD patients and found four times higher levels of BALF sTREM-1 in PS patients (P = 0.001). We also recorded the effect of smoking, ILD smokers had higher sTREM-1 levels than non-smokers (P = 0.0019). Higher concentrations of sTREM-1 were detected in BALF of patients with lymphadenopathy and with elevated inflammatory markers in BALF. Our results show that BALF sTREM-1 could be a good inflammatory marker and could help in diagnosis and PS monitoring. Detection of sTREM-1 in BALF indirectly points to myeloid cells activation in the lungs and helps to complete the information about the number of myeloid cells commonly determined in BALF with additional information concerning the intensity of their activation. This is the first study that analyses BALF sTREM-1 levels in patients with PS (Tab. 8, Ref. 28). Text in PDF www.elis.sk.

Background: Discussions on raising pension eligibility age focus more on improvement in life expectancy (LE) and health expectancy measures than on socioeconomic differences in these measures. Therefore, this study assesses the level of socioeconomic differences in these two measures in Western-Europe., Methods: Data from seven annual waves (1995-2001) of the European Community Household Panel were used. Health and socioeconomic information was collected using standardised questionnaires. Health was measured in terms of disability in daily activities. Socioeconomic status was determined as education level at baseline. Multi-state Markov modelling was applied to obtain age-specific transition rates between health states for every country, educational level and gender. The multi-state life table method was used to estimate LE and disability free life expectancy (DFLE) according to country, educational level and gender., Results: When comparing high and low educational levels, differences in partial DFLE between the ages 50 and 65 years were 2.1 years for men and 1.9 years for women. At age 65 years, for LE the difference between high and low educated groups was 3 years for men and 1.9 years for women, and for DFLE the difference between high and low educated groups was 4.6 years for men and 4.4 years for women. Similar patterns were observed in all countries, although inequalities tended to be greater in the southern countries., Conclusions: Educational inequalities, favouring the higher educated, exist on both sides of the retirement eligibility age. Higher educated persons live longer in good health before retirement and can expect to live longer afterwards.

Background and Objective: Chemotherapy for advanced non-small-cell lung cancer (NSCLC) remains marginally effective, with a 5-year overall survival rate of approximately 5%. Recently, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was approved in Slovakia for the treatment of metastatic NSCLC. Gefitinib is a selective EGFR inhibitor that binds to the adenosine triphosphate binding pocket of the kinase domain and blocks downstream signaling pathways. Mutations of the EGFR gene, particularly an in-frame 15 bp deletion (delE746&#95;A750) in exon 19 and the L858R mutation in exon 21, correlate with enhanced clinical responsiveness to EGFR tyrosine kinase inhibitors. However, the detection of these mutations and thereby prediction of the therapy outcome is sometimes unreliable due to the low sensitivity of direct sequencing if the proportion of tumor cells in the tissue is less than 25%. Therefore we decided to test the applicability of other methods, particularly high-resolution melting analysis (HRMA), for detection of these mutations in clinical samples., Methods: We analyzed 53 archival cytologic specimens for the presence of EGFR mutations, using the HRMA method. Results were verified by direct sequencing. For samples containing less than 25% tumor cells, we used mutant-enriched PCR before sequencing. We also performed a titration assay to establish the lower limit of the proportion of tumor cells for detection of EGFR mutations., Results: EGFR mutations were detected in 13 cases (24%). In-frame deletions in exon 19 were detected in eight cases (15%) and the L858R mutation in exon 21 was detected in five cases (9%). The positive results of the HRMA were confirmed by direct sequencing only in five of 13 cases. In the remaining eight positive samples, HRMA results were confirmed by sequencing analysis after mutant-DNA enrichment. The titration assay established that the lower limit for detection of EGFR mutations by HMRA was 1% tumor cells in the clinical sample., Conclusion: Our results indicated that HRMA in combination with mutant-enriched PCR represents a sensitive method for detection of EGFR mutations from cytologic specimens. When properly executed, this protocol allows identification of EGFR mutations in specimens containing a minimal percentage of tumor cells.

In combination with high-resolution ultrasound (US), vacuum-assisted biopsy (VB) techniques can be used for accurate diagnosis confirmation and therapeutic minimally invasive removal of benign breast lesions. We developed a gel-simulation model to imitate the removal of benign breast lesions (e.g., fibroadenoma) with VB from a turkey breast-phantom. Bilobular US-sensitive models in the form of a fibroadenoma were manufactured from flexible, cuttable synthetic material (longitudinal diameters of 4-20 mm). They were implanted in turkey meat and vacuum biopsied under 2-D and 3-D imaging with 11G and 8 G needles. The minimum number of cylinders removed per tumour volume, the maximum complete excision tumour size and the optimum needle gauge were determined. Lesions with a longitudinal diameter of up to 10 to 12 mm could be removed with the 11G needle, those up to 20 mm with the 8G needle. The values for the correct needle size, number of cylinders per tumour size to be removed produced with the gel turkey phantoms provide a reference for clinicians performing VB with total excision intent. VB is suitable for the removal of benign lesions with a diameter of up to 20 mm.

Tracheal stenosis is a serious, life-threatening disease with an increasing tendency. The number of complicated tracheal lesions, where resection and anastomosis can not be performed, still increases and the situation requires solution by endoprosthesis. Consequent the management of such complicated obstructive tracheal lesions is individual and time-consuming. The main objective of this study is to review the single institution experience with central airways stenosis treatment and to define the role of endotracheal stenting in tracheal reconstruction surgery. This study presents the retrospective analysis of tracheal stenosis reconstruction by means of our own modification of Montgomery T-tube. (Tab. 3, Fig. 3, Ref. 12.)

A group of 89 patients suffering from tracheostenosis was studied in the period from January 1990 to January 1999. Surgical procedure on trachea was performed in 63 patients with postintubation (posttracheostomic) stenosis, in 6 patients with direct tracheal trauma, in 9 with tracheoesophageal fistula, in 7 with malignant stenosis, in 3 with postinflammatory subglottic stenosis. In the treatment of tracheal stenosis a set of methods was used ranging from laser and tracheal endoproteses, through cartilage implantation and plastic reconstruction of tracheal defects to extensive segmental resections. In a group of 50 patients with segmental resection in 43 (%) of them the result was good, in 2 (4%) of them satisfying, in 4 (8%) of them temporary brace (on T-cannule) persists, 1 patient died in postoperative period (2%). In a group of 39 patients with combined conservative treatment in 18 patients good results were reached (43.8%), in 6 satisfying (15.4%), in 13 of them temporary brace (on T-cannule) persists (33.3%) and 2 died in postoperative period (5.1%). In conclusion the results of this work suggest that the most frequent indication for surgical treatment is postintubation (postracheostomy) stenosis and that segmental trachea resection has priority in the treatment of tracheal stenoses. (Tab. 2, Ref. 18.)

Maintaining sufficient airflow in the distal airways during tracheal resection remains to be a challenging task. Disadvantages of cross-field intubation are well known. Experiences with using two models (CHIRAJET NCA and PARAVENT PAT) of ventilators for High Frequency Jet Ventilation (HFJV) during 82 resection of trachea (94 applications) are reported. Postintubation or post-tracheostomy stenosis required surgery in 76% of the cases. 11% of the cases required surgery for tumour stenosis. In 4/82 cases trauma necessitated the trachea surgery. Six tracheo-esophageal fistulas were operated on using this technique. No perioperative technique related complications was encountered. No perioperative and early postoperative mortality was noted. The usage of HFJV is method of first choice in our experience, especially in lesions of upper part of the trachea. It proved to be safe, effective and easy to use ventilation technique.

Background: Tracheal stenosis is a serious disease of the upper airways. With advances in resuscitation its incidence is steadily increasing. Despite modern therapeutic procedures and the use of perfect materials tracheal stenosis is still a serious therapeutic problem., Methods and Results: The authors present a group of 48 patients with tracheal stenosis treated during the period between January 1990 and September 1995. Thirty-eight patient with postintubation stenosis were subjected to surgery. 4 with direct tracheal injury, 5 with a tracheoesophageal fistula and one with a malignant stenosis of the trachea. For treatment of tracheal stenosis a wide range of therapeutic procedures was used: from laser destruction to long-term stenting on a T cannula and plastic reconstruction of tracheal defects to extensive segmental resections of the trachea. In the group of patients with segmental resection of the trachea (21 patients) in 17 good results were achieved (81%), in three satisfactory results (14%) and one patient died during the postoperative period. In the group with combined treatment (27 patients) in 13 good results were recorded (48%), in three satisfactory results (11%), in nine patients treatment still proceeds (33%) their prognosis in uncertain. During the postoperative period two patients died., Conclusions: From the results of the work the authors conclude that segmental resection of the trachea holds a priority position in the treatment of tracheal stenoses. It gives the best immediate and late therapeutic results. It is important to emphasize prevention of tracheal stenoses during prolonged controlled ventilation. Because the most difficult tracheal reconstructions are those after unsuccessful primary reconstructions, it is essential to concentrate serious tracheal lesions in departments which have adequate staff and technical equipment and ample experience.