Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype

Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known. Methodology/Principal Findings: Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications. Conclusions/Significance: The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.Original Publication:Charlotte Gustafsson (Lidström), Jenny Mjösberg, Andreas Matussek, Robert Geffers, Leif Matthiesen, Göran Berg, Surendra Sharma, Jan Buer and Jan Ernerudh, Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype, 2008, PLoS ONE, (3), 4, e2078.http://dx.doi.org/10.1371/journal.pone.0002078Copyright: Public Library of Science (PLoS)http://www.plos.org

New pharmacological strategies in the treatment of nonsmall cell lung cancer

According to the number of deaths lung cancer is the leading cancer type, and non-small cell lung carcinoma (NSCLC) is the most frequent subtype. Because of high NSCLC morbidity the aim of this paper is to discuss the appearance of new pharmacological possibilities in the lung cancer therapy. In the research field of new drugs there are two approaches that differ from the standard chemotherapy. According to one approach targeted therapy against specific molecules in the cancer cells is considered, like inhibitors of growth factors, or inhibitors of cell signalling (e.g. tyrosine kinase inhibitors, serine-threonine inhibitors), while on the other hand, drugs that could induce immune system in order to destroy lung cancer (like inhibitors of programmed death receptors, their ligands, or MAGE-A3 antagonists) are on the way to be discovered. Some of these drugs are approved by the U.S. Food and Drug Administration, while the others are in the first phases of clinical trials

Hypogonadism in chronic obstructive pulmonary disease (COPD) - risk factors

© 2019 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Bacground/Aim. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality in pulmonary pathology. However, apart from its own pulmonary manifestations, this disease is also characterized by systemic effects, including hypogonadism which is described especially in the group of men with COPD. The aim of this study was to evaluate risk factors for hypogonadism in men with COPD. Methods. The study included 96 male patients with COPD in stable phase of the disease. All patients were checked for concentration of free testosterone in serum, markers of systemic inflammation, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and C reactive protein (CRP), pulmonary function test, gas exchange parameters, a 6-minute walk test (6MWT), nutritional status and condition of skeletal muscle (midthigh muscle cross-sectional area - MTCSA using computed tomography). Results. Decreased value of free testosterone was found in 37.5% of the patients. In the group with hypogonadism (free testosterone < 4.5 pg/mL), we found significantly increased serum concentration of TNF-α (5.88 ± 3.21 vs. 3.16 ± 2.53 pg/mL; p < 0.05), significantly lower MTSCA (68.2 ± 18.72 vs. 91.1 ± 21.4 cm2; p < 0.05) and the 6MWT (268.33 ± 32.35 vs. 334.25 ± 43.25 m; p < 0.05). Lung function, gas exchange markers and body mass index (BMI) were similar in both groups. The multivariate regression analysis singled out serum value of TNF-α as an independent predictor of serum concentrations of free testosterone (B = -0.157; 95% confidence interval: -0.262-0.053). Conclusion. In our analysis we found that TNF-α as a marker of systemic inflammation is an independent predictor of the presence of hypogonadism in the patients with COPD. Our results indicate that hypogonadism predisposes to skeletal muscle wasting and exercise intolerance in male COPD patients

Churg-strauss vasculitis in patient who received montelukast

© 2018, Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Introduction. Montelukast is a selective leukotriene receptor antagonist. One of side effects of this drug class is the Churg-Strauss syndrome (CSS). There is still no reliable evidence whether the expression of this syndrome could be masked by high doses of corticosteroids and become expressed by termination of corticosteroid use, or whether it could be a consequence of leukotriene receptor antagonists use. Case report. Female patient, aged 49 years, was hospitalized with symptoms of fever, dyspnea, cough and increased sputum production with occasional hemoptysis. She was treated for asthma during the previous year. Leukocyte differential formula registered 44% of eosinophils. IgE value was extremely elevated, with value measured to 580 kU/L and eosinophile cation protein value was 15.1 μg/L. Computed tomography of the chest described changes in the form of ground glass located in all lobes of the right lung and in the upper lobe of the left lung. Computed tomography of paranasal sinuses described changes that could resemble to polyposis, chronic sinusitis, and possible granulomatosis. Mononeuritis of peroneal nerve of the right leg was proven by electromyographic examination. Bone marrow biopsy indicated hypercellularity with domination of eosinophilic granulocytes (30%). Five out of six criteria were noted in patient’s clinical presentation, after which the diagnosis of CSS was set. The patient began treatment with high doses of corticosteroids while montelukast was discontinued which resulted in disease remission. Conclusion. Although there is no evidence that leukotriene modifiers cause the CSS in all patients with asthma, in case of frequent exacerbations with the appearance of pulmonary infiltrates, eosinophilia and paranasal sinus abnormalities make one think of this form of vasculitis

Community-acquired pneumonia: Economics of inpatient medical care vis-à-vis clinical severity

© 2015, Sociedade Brasileira de Pneumologia e Tisiologia. All rights reserved. Objective: To assess the direct and indirect costs of diagnosing and treating community-acquired pneumonia (CAP), correlating those costs with CAP severity at diagnosis and identifying the major cost drivers. Methods: This was a prospective cost analysis study using bottom-up costing. Clinical severity and mortality risk were assessed with the pneumonia severity index (PSI) and the mental Confusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65) scale, respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed CAP. The analysis was run from a societal perspective with a time horizon of one year. Results: Expressed as mean ± standard deviation, in Euros, the direct and indirect medical costs per CAP patient were 696 ± 531 and 410 ± 283, respectively, the total per-patient cost therefore being 1,106 ± 657. The combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and 38,979 in direct and indirect costs, respectively). The major cost drivers, in descending order, were the opportunity cost (lost productivity); diagnosis and treatment of comorbidities; and administration of medications, oxygen, and blood derivatives. The CURB-65 and PSI scores both correlated with the indirect costs of CAP treatment. The PSI score correlated positively with the overall frequency of use of health care services. Neither score showed any clear relationship with the direct costs of CAP treatment. Conclusions: Clinical severity at admission appears to be unrelated to the costs of CAP treatment. This is mostly attributable to unwarranted hospital admission (or unnecessarily long hospital stays) in cases of mild pneumonia, as well as to over-prescription of antibiotics. Authorities should strive to improve adherence to guidelines and promote cost-effective prescribing practices among physicians in southeastern Europe

Difficulties in diagnosis of tuberculosis without bacteriological confirmation in a 15-year-old boy after the contact with a patient with tuberculosis – A case report

© 2018, Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Introduction. After the contact with a patient suffering from tuberculosis (TB), previously healthy children have 1%–16% possibility to develop the disease. TB diagnosis in children is not easy to confirm so 15%–25% of cases remain undiagnosed. Case report. A 15-yearold- boy was hospitalized with productive cough, pain in the right flank area, fever, and fatigue, loss of appetite and night sweats. One of the boy's uncles was cured of tuberculosis, another uncle had active tuberculosis and both of them were in contact with the boy, but they did not live in the same household. During the physical examination, the child was febrile, with dyspnea, pale, with profuse sweating, debilitate. BCG (Bacillus Calmette – Guérin) scar was present. The auscultatory findings of the lungs showed quiet breathing from the scapula to the right lung base and chest radiography suggested massive right sided pleuropneumonia. The parameters of the inflammation were high and Mycobacterium tuberculosis (MTB) was not found in the samples of sputum and gastric lavage. Pleural puncture revealed exudative nature in the aspirated fragment. Cytology was nonspecific, the MTB was not found and the planted surfaces on Lowenstein-Jensen remained sterile. Tuberculin skin test (TST) – Mantoux was positive (+ 10 mm), Interferon Gamma Release Assay (QuantiFERON- TB GOLD In-Tube) was negative. The boy was unsuccessfully treated with broad spectrum antibiotics. By video-assisted thoracoscopy, the pleural tissue clip confirmed the benign chronic granulomatous process, while histochemical staining did not show MTB. The treatment with anti-TB medication led to clinical and radiographic recovery. The boy is now in good general condition, without consequences of the disease. Conclusion. This case report pointed out the importance of risk factors and difficulties in diagnosing TB in children

Unusual respiratory manifestations of ankylosing spondylitis a case report

© 2016, University of Kragujevac, Faculty of Science. All rights reserved. A male patient, 54 years old, was initially admitted to the hospital because of fatigue he felt during the last month and swelling of the lower legs. Upon hospital admittance, gas exchange analysis showed global respiratory failure: pO2=6.1 kPa, pCO2=10.9 kPa, pH=7.35, A-a gradient = 1.0. Due to the existence of hypercapnia and decompensated respiratory acidosis, the patient was connected to a device for non-invasive mechanical ventilation. Reduced chest mobility was noticed, and the respiratory index value was decreased. Radiographs of the chest and thoracic and lumbo-sacral spine showed marked changes on the spine attributable to ankylosing spondylitis (AS). Radiographs of the sacroiliac joints showed reduced sacroiliac joint intraarticular space with signs of subchondral sclerosis. e diagnosis of AS was set on the basis of New York Criteria (bilateral sacroiliitis, grade 3) and clinical criteria (back pain, lumbar spine limitation and chest expansion limitation). HLA typing (HLA B27 +) confirmed the diagnosis of AS. Pulmonary function test proved severe restrictive syndrome. Polysomnography verifi ed the existence of severe obstructive sleep apnoea (AHI =73). is was a patient with newly diagnosed AS, with consequent severe restrictive syndrome and global respiratory failure with severe obstructive sleep apnoea. e patient was discharged from the hospital with a NIV (global respiratory failure) device for home use during the night

Characteristics of copd phenotypes in serbia

Background: Establishing a regional/national/international registry of patients suffering from chronic obstructive pulmonary disease (COPD) is essential for both research and healthcare, because it enables collection of comprehensive real-life data from a large number of individuals. Objective: The aim of this study was to describe characteristics of COPD patients from the Serbian patient registry, and to investigate actual differences of those characteristics among the COPD phenotypes. Methods: The Serbian registry of patients with COPD was established in 2018 at University of Kragujevac, Faculty of Medical Sciences, based on an online platform. Entry in the Registry was allowed for patients who were diagnosed with COPD according to the following criteria: symptoms of dyspnea, chronic cough or sputum production, history of risk factors for COPD and any degree of persistent airflow limitation diagnosed at spirometry. Results: In the Serbian COPD registry B and D GOLD group were dominant, while among the COPD phenotypes, the most prevalent were non-exacerbators (49.4%) and then frequent exacerbators without chronic bronchitis (29.6%). The frequent exacerbator with chronic bronchitis phenotype was associated with low levels of bronchopulmonary function and absolute predominance of GOLD D group. Anxiety, depression, insomnia, hypertension and chronic heart failure were the most prevalent in the frequent exacerbator with chronic bronchitis phenotype; patients with this phenotype were also treated more frequently than other patients with a triple combination of the most effective inhaled anti-obstructive drugs: long-acting muscarinic antagonists, long-acting beta 2 agonists and corticosteroids. Conclusion: In conclusion, the data from the Serbian registry are in line with those from other national registries, showing that frequent exacerbators with chronic bronchitis have worse bronchopulmonary function, more severe signs and symptoms, and more comorbidities (especially anxiety and depression) than other phenotypes. Other studies also confirmed worse quality of life and worse prognosis of the AE-CB phenotype, stressing importance of both preventive and appropriate therapeutic measures against chronic bronchitis

Influence of inhaler technique on asthma and COPD control: a multicenter experience

Aleksandra Dudvarski Ilic,1,2 Vladimir Zugic,1,2 Biljana Zvezdin,3,4 Ivan Kopitovic,3,4 Ivan Cekerevac,5,6 Vojislav Cupurdija,5,6 Nela Perhoc,7 Vesna Veljkovic,7 Aleksandra Barac8 1Faculty of Medicine, University of Belgrade, 2Clinic for Pulmonology, Clinical Centre of Serbia, Belgrade, 3Faculty of Medicine, University of Novi Sad, Novi Sad, 4Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, 5Faculty of Medicine, University of Kragujevac, 6Clinic for Pulmonology, Clinical Centre Kragujevac, Kragujevac, 7Clinic for Pulmonary Diseases Knez Selo, Clinical Centre Nis, Nis, 8Faculty of Stomatology, University Academy of Business Novi Sad, Novi Sad, Serbia Background: The successful management of asthma and chronic obstructive pulmonary disease (COPD) mostly depends on adherence to inhalation drug therapy, the usage of which is commonly associated with many difficulties in real life. Improvement of patients&rsquo; adherence to inhalation technique could lead to a better outcome in the treatment of asthma and COPD.Objective: The aim of this study was to assess the utility of inhalation technique in clinical and functional control of asthma and COPD during a 3-month follow-up.Methods: A total of 312 patients with asthma or COPD who used dry powder Turbuhaler were enrolled in this observational study. During three visits (once a month), training in seven-step inhalation technique was given and it was practically demonstrated. Correctness of patients&rsquo; usage of inhaler was assessed in three visits by scoring each of the seven steps during administration of inhaler dose. Assessment of disease control was done at each visit and evaluated as: fully controlled, partially controlled, or uncontrolled. Patients&rsquo; subjective perception of the simplicity of inhalation technique, disease control, and quality of life were assessed by using specially designed questionnaires.Results: Significant improvement in inhalation technique was achieved after the third visit compared to the first one, as measured by the seven-step inhaler usage score (5.94 and 6.82, respectively; P&lt;0.001). Improvement of disease control significantly increased from visit 1 to visit 2 (53.9% and 74.5%, respectively; P&lt;0.001) and from visit 2 to visit 3 (74.5% and 77%, respectively; P&lt;0.001). Patients&rsquo; subjective assessment of symptoms and quality of life significantly improved from visit 1 to visit 3 (P&lt;0.001).Conclusion: Adherence to inhalation therapy is one of the key factors of successful respiratory disease treatment. Therefore, health care professionals should insist on educational programs aimed at improving patients&rsquo; inhalation technique with different devices, resulting in better long-term disease control and improved quality of life. Keywords: Turbuhaler, adherence, inhalation technique, asthma, COP

Bochdalek hernia in adults – A case report

© 2018, Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Introduction. Asymptomatic Bochdalek hernia in adults is a rarity. The aim of this paper is to present a rare case of Bochdalek hernia among adults and to point out to significance of clinical suspicion and important role of imaging techniques in reaching the exact diagnosis of this abnormality. Case report. A patient, aged 68 years, came to the Clinic of Pulmonology complaining of constant dyspnea, coughing and fatigue. Computed tomography (CT) findings were dominated by the large rear right diaphragmatic hernia with the hernial sac that reached the carina trachea and urged the principal bronchi. The stomach, duodenum and proximal part of jejunal winds, as well as a greater amount of omental and mesenteric adipose tissue were localized in hernial sac. Radiography of gastroduodenum showed: entry of the esophagus into the cardia was in the level of the right main bronchus. Stomach was mainly located in the chest (cardia, upper corpus half - to the level of the right main bronchus). Operation was indicated. First, we made right thoracotomy and the hernia sac was separated from the right lung and then we performed median laparotomy and the contents of the hernia sac were returned to the abdominal cavity; diaphragm defect was reconstructed with prolen mesh. Conclusion. We presented a rare case of right sided Bochdalek hernia which was discovered at late age and surgically treated with success