Predictions for Z-Boson Production in Association with a b-Jet at O(α_{s}

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.

TREM-1 and TREM-2 Expression on CD14+ Cells in Bronchoalveolar Lavage Fluid in Pulmonary Sarcoidosis and Hypersensitivity Pneumonitis in the Context of T Cell Immune Response.

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.

Genotyping of EGFR Mutations from Bronchial Cytological Specimens in Slovakian Lung Cancer Patients.

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.

The value of SHOX2 methylation test in peripheral blood samples used for the differential diagnosis of lung cancer and other lung disorders.

Methylation of the cytosine residues within the CpG dinucleotides plays an important role in the fundamental cellular processes, human diseases and even cancer. The DNA methylation represents a very stable sign and therefore may be used as a valuable marker for cancer screening. Epigenetic cancer biomarkers are independent of classical morphology and thus show extensive potential to overcome the limitations of cytology. Several epigenetic cancer markers have been reported to be detectable in body fluids such as bronchial aspirate, sputum, plasma and serum.Short stature homeobox gene 2 (SHOX2) encodes a homeo-domain transcription factor, which has been identified as a close homologue of the SHOX gene and both genes are involved in skeletogenesis and heart development. Methylation of SHOX2 gene has been shown to be present at high prevalence in carcinomas of lung, however may also be used to identify other tumour entities.In the presented study, we have compared suitability of two types of material associated with lung cancer for the detection of SHOX2 methylation. We have confirmed that methylation of SHOX2 gene represents reliable marker of lung malignancies. The parallel tests in the blood plasma revealed that it may represent a good alternative material for testing of the SHOX2 methylation, making the test available to patients who are unable to undergo bronchoscopy.

Increased antifungal antibodies in bronchoalveolar lavage fluid and serum in pulmonary sarcoidosis.

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 ß-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.

Diagnostic value of TREM-1 and TREM-2 expression in bronchoalveolar lavage fluid in sarcoidosis and other lung diseases.

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).

sTREM-1 in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis, effect of smoking and inflammation.

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.

Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial.

BACKGROUND: Surgical resection of gastrointestinal stromal tumour (GIST) is rarely curative in patients at high risk of tumour recurrence and therefore 1 year of post-surgery adjuvant imatinib therapy has been recommended in this sub-group. Recently, adjuvant imatinib therapy administered for 3 years has been demonstrated to further increase recurrence-free survival and overall survival. The goal of this study was to assess the economic value of extending the duration of adjuvant imatinib therapy in high-risk patients in the Netherlands. METHODS: A multistate Markov model was developed to simulate how patients' clinical status after GIST excision evolves over time until death. The model structure encompassed four primary health states: free of recurrence, first GIST recurrence, second GIST recurrence, and death. Transition probabilities between the health states, data on medical care costs, and quality-of-life were obtained from published sources and from expert opinion. RESULTS: The expected number of life years (or quality-adjusted life years, QALYs) was higher in the 3-year group than in the 1-year group, 8.91 (6.55) and 7.04 (5.18) years, respectively. In the 3-year and 1-year group, the expected total costs amounted to €120,195 and €79,361, of which, €74,631 (62%) and €27,619 (35%) were adjuvant therapy drug costs, respectively. The difference in health benefits, that is 1.87 life years or 1.37 QALYs, and costs, €40,835, resulted in incremental cost-effectiveness ratios (ICER) of €21,865 per life year gained, and €29,872 per QALY gained. LIMITATIONS: A limitation of the study was inherently related to the uncertainty around the predictions of RFS. Scenario analyses were conducted to test the sensitivity of different RFS predictions on the results. CONCLUSIONS: Delayed recurrence due to treatment with longer-term adjuvant imatinib therapy represents a cost-effective treatment option with an ICER below the generally accepted threshold in the Netherlands.

Socioeconomic inequalities in life and health expectancies around official retirement age in 10 Western-European countries.

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.

Epidemiology of osteoporosis related fractures in Hungary from the nationwide health insurance database, 1999-2003.

UNLABELLED: The Hungarian national health insurance database was screened for fractures of patients aged 50-100, 1999-2003. On average, there were 343 hip, 1,579 forearm, 342 proximal humerus, 48 inpatient vertebral and 2,459 other fractures/100,000 inhabitants/year. INTRODUCTION: The incidence of fractures differs among populations. Our aim was to study the incidence of fractures in Hungary, focusing on classical osteoporotic sites and to compare the results with those of other European countries. METHODS: The Hungarian National Health Insurance Fund database, covering 100% of the population, was screened for fractures of patients aged 50-100, 1999-2003. The search of vertebral fractures was restricted to those admitted to hospital. A gender and age-matched comparison was performed with available data from Europe. RESULTS: There were mean 343 hip, 1,579 forearm, 342 proximal humerus, 48 inpatient vertebral and 2,459 other fractures/100,000 inhabitants/year; the female/male ratio was between 1.2-2.4. Multiple fractures occurred in 23.1% of the cases. Hip fracture incidence in Hungary lies between the rates of northern and southern countries of Europe. CONCLUSIONS: Our study offers nationwide epidemiological data on fractures in Hungary. The incidence of fractures increased by age, regardless of the type of fracture. Incidence of hip fractures in Hungary fits in the previously established geographic trends in Europe. Our results fulfil a need for fracture data from Central Europe.

Complete extirpation of benign breast lesions with an ultrasound-guided vacuum biopsy system.

OBJECTIVES: To investigate whether ultrasound-guided vacuum biopsy (VB) with curative intent is suitable for the complete extirpation of selected sonographically detectable benign lesions of the breast, and to establish the limitations of the method with regard to lesion size and complications, the extent of scar formation and the prognostic value. METHODS: One hundred and nine patients underwent hand-held, ultrasound-guided VB (8G or 11G needle) between June 2000 and September 2003. Of these, 45 (41%) women underwent ultrasound-guided extirpation of 46 lesions, and 42 women with 43 lesions were followed up clinically and sonographically for an average of 5.9 months. The complete extirpation rate, residual lesions, and patient satisfaction with the intervention were evaluated. RESULTS: Removal of all sonographic evidence of lesions (median diameter, 13 mm) was achieved in 86% of cases (8G needle, 80%; 11G needle, 89%). 19% of the patients had suspected scar formation at the biopsy site. A palpable lesion in the breast could be removed by VB in 90% of cases. None of the patients developed infections and there were no hemorrhages requiring intervention, or damage to the skin or chest wall. A total of 95% of the patients stated that they would prefer this approach to open excision for possible future intervention. CONCLUSIONS: VB is an ambulatory procedure associated with a low degree of pain. It has a high degree of patient acceptance and, as a minimally invasive biopsy technique for benign lesions, is a good alternative to open excision. The rate of complications is low and is similar to that observed with conventional microbiopsy.

Central airways stenoses management--a single institution experience.

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.)

[Tracheal stenosis and its treatment]. / Stenóza trachey a jej liecba.

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.)

High frequency jet ventilation in trachea reconstructions--its advantages in our experience.

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.

[Therapy of tracheal stenoses]. / Liecebné moznosti tracheálnej stenózy.

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.