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Aim To analyse the resolution of chest X-ray findings in relation to laboratory parameters in patients infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a two- month followup. Analysis of chest X-ray findings in the first few months after the disease is the main goal of our work. Methods Out of the total of 343 patients chest X-ray findings were followed in 269 patients. Patients were divided into groups according to the severity of findings. D-dimer, inflammatory markers, blood cell count, neutrophil lymphocyte ratio (NLR) were analysed. Chest X-ray was analysed during the hospitalization on the day of admission, on the third, the seventh and the fourteenth day (scoring method was used). After discharge chest X-ray was performed in a two-week follow-up, then after one and two months, and after three months if necessary. Results Incomplete chest X-ray resolution was identified in 24 (39.34%) patients with severe, 27 (22.31 %) patients with moderate and in three (3.91%) patients with mild findings. Statistical significance was established in overall score by comparison between all groups (p<0.001), and in the moderate compared to the mild group (p=0.0051). The difference of NLR in the severe compared to the moderate group was observed (p=0.0021) and in the severe group compared to the mild group (p=0.00013). Conclusion Chest X-ray findings persisted mostly in the severe group followed by the moderate and mild ones. Long-term followup is necessary for the appropriate treatment and prevention of fibrosis, and reduction of symptoms.

E. Jusufovic, V. Žugić, M. Košnik, M. Drvenica, S. Hromis, J. Nurkić, M. Al‐Ahmad, L. B. Kardum et al.

E. Jusufovic, M. Košnik, J. Nurkić, N. Arifhodzic, M. Al‐Ahmad, L. Bulat-Kardum, M. Bećarević, M. Osmić et al.

Despite multistep efforts many asthma patients remain symptomatic. Anti-inflammatory activities of curcumin were shown. Aim was to analyse the add-on therapy with curcumin on inflammatory parameters, lung function, disease control and quality of life in asthma patients. 150 non-smokers with moderate partially controlled asthma were treated during 3 months with stable moderate dose of inhaled glucocorticoids and divided into three groups (n=50): curcumin group (receiving curcumin 500 mg per os twice daily), placebo and control group. Before study, sputum eosinophils (sEo), blood eosinophils (bEo), high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) were similar between groups. After study, FEV1%, ACT and AQLQ were improved in all groups, but these improvements were more prominent in curcumin group than in placebo and control. Additionally curcumin group only showed improvement in sEo, bEo and hsCRP. Furthermore, curcumin group showed also more frequent clinically significant improvement in ACT score (change>3) and in AQLQ score (change≥0.5) when compared to placebo and control. However, placebo and control showed similar distribution in FEV1%, ACT, AQLQ, hsCRP, sEo and bEo after study. This is the first placebo controlled and single-blind study to suggest that add-on therapy with curcumin could improve lung function, disease control and quality of life in moderate partially controlled asthma. Future studies may benefit from a larger sample size, longer study duration, double blind design, different dose of curcumin and/or improvements in oral bioavailability.

E. Jusufovic, M. Košnik, J. Nurkić, N. Arifhodzic, M. Al‐Ahmad, L. B. Kardum, M. Bećarević, M. Osmić et al.

Sputum eosinophils might predict response to inhaled corticosteroids (ICS) in patients with advanced chronic obstructive pulmonary disease (COPD). Induction of sputum requires expertise and may not always be successful. Aim was to investigate correlation and predictive relationship between peripheral blood eosinophils (bEo) and sputum eosinophils (sEo), and impact of peripheral blood eosinophilia on outcome of COPD exacerbation. 120 current smokers with COPD (GOLD group C) (57.4 ± 0.92 years, M/F ratio 1.4), with no blood (≥7% or >0.43x109/L) nor sputum (≥3%) eosinophilia, were treated with moderate dose of ICS and long-acting bronchodilatator during stable disease, but systemic corticosteroids and antibiotics during exacerbation. According to sputum eosinophilia (≥4%) during exacerbation, patients were divided into eosinophilic (n=45) and non-eosinophilic group (n=75). In stable disease, bEo and sEo were similar in both groups (p>0.05). During exacerbation, bEo and sEo were significantly higher in eosinophilic group (eosinophilic vs. non-eosinophilic: blood: 1.42 ± 0.39 x109/l vs. 0.23 ± 0.02 x109/l, p<0.001; sputum: 8% (4, 19) vs. 1% (0, 3), p<0.0001), but bEo correlated with sEo in both groups (eosinophilic: r=0.52, p<0.001; non-eosinophilic: r=0.25, p<0.05). Relative bEo predicted sputum eosinophilia (area under the curve=0.71, standard error=0.05; 95% confidence interval [CI] =0.61-0.81; p<0.001) and enabled identification of the presence or absence of sputum eosinophilia in 82% of the cases at a threshold of ≥4% (specificity=83.56%, sensitivity=93.83%, positive likelihood ratio=3.67). Eosinophilic group during exacerbation showed less frequent hospitalisations and shorter exacerbation (eosinophilic vs. non-eosinophilic: hospitalisations: 26.7% vs. 60.0%, p<0.001; duration of exacerbation (days): 8.1±0.35 vs. 10.13±0.31, p<0.0001). In COPD exacerbation, relative peripheral blood eosinophils ≥4% might identify sputum eosinophilia. Blood eosinophilia indicate better outcome of COPD exacerbation. Further investigations are needed to predict eosinophilic exacerbation in COPD patients, with prior absence of sputum or blood eosinophilia.

Background: Despite multistep efforts, many asthma patients remain symptomatic. Anti-inflammatory activities of curcumin are shown. Aim of the study was to analyse the impact of curcumin add-on therapy on inflammatory parameters, lung function, disease control and quality of life in asthma patients. Subjects and methods: Three-months lasting study was done on 150 non-smokers with asthma, that were treated with stable, moderate dose of inhaled glucocorticoids (IGK) and divided into three groups (n=50 each): curcumin group (receiving curcumin 500 mg per os twice daily), placebo group (receiving placebo tablets) and control (non-intervention) group. Sputum eosinophils (sEo), blood eosinophils (bEo), high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and mini Asthma Quality of Life Questionnaire (mAQLQ) were compared before and after study, as well as between groups. Results: Before study, all followed parameters were similar between groups. After study, FEV1%, ACT and AQLQ were improved in all groups, but these improvements were more prominent in curcumin group than in placebo and control. Additionally curcumin group only showed improvement in sEo, bEo and hsCRP. Furthermore, curcumin group showed more frequent clinically significant improvement in ACT score (change>3) and in mAQLQ score (change≥0.5) when compared to placebo and control. On the other side, after study FEV1%, ACT, mAQLQ, hsCRP, sEo and bEo were similarly distributed among placebo and control group. Conclusion: This is the first placebo controlled and single-blind study to suggest that add-on therapy with curcumin could improve lung function, disease control and quality of life in moderate partially controlled asthma. Future studies may benefit from a larger sample size, longer study duration, double blind design, different dose of curcumin and/or improvements in oral bioavailability.

E. Jusufovic, M. Košnik, Azra Jusufovic, M. Bećarević, M. Al‐Ahmad, J. Nurkić, M. Osmić, Alma Nadarević et al.

Despite intensive treatment, considerable proportion of patients with asthma remains symptomatic. Anti-inflammatory activity of curcumin has been shown. Aim: analyse the impact of add-on therapy with curcumin in asthma patients on inflammatory parameters, lung function and asthma control. During 2 months, 100 non-smokers (46.8±12.4 years, F/M ratio 1.04) with moderate, partially controlled asthma were treated with moderate dose of inhaled glucocorticoids (IGK) with no changes in dose. Patients were divided into two groups (n=50): curcumin group receiving curcumin 500 mg per os twice daily and control group. Before study, sputum and blood eosinophils (Eo), blood neutrophils, high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) were similar between groups. After study, in curcumin group blood Eo count and hsCRP decreased, and FEV1, ACT and AQLQ increased significantly (before vs. after study: Eo: 5.9±0.6 vs. 4.1±0.4; hsCRP: 4.2±0.3 vs. 3.4±0.2; FEV1%: 77.7±0.8 vs. 83.9±0.5; ACT: 14.5 (6,19) vs. 18 (14,21); AQLQ: 3.4±0.2 vs. 4.1±0.2). There was no change in the control group. Compared to control curcumin group showed significantly lower blood Eo and hsCRP and higher FEV1% (curcumin vs. control: Eo: 4.1±0.4 vs. 5.4±0.5; hsCRP: 3.4±0.2 vs. 4.0±0.3; FEV1%: 83.9±0.5 vs. 78.3± 0.8), and improved ACT and AQLQ (ACT change>3: 72% vs. 28%; AQLQ change>0.5: 54% vs. 32%) after study. Add-on therapy with curcumin in patients with moderate partially controlled asthma seems to improve response to IGK regarding lung function, asthma control and quality of life. Further placebo controlled trials are needed.

B. Prnjavorac, R. Sejdinović, E. Jusufovic, J. Mehić, O. Bedak, Jasmin A Fejzic, Nedžada Irejiz, M. Malenica et al.

Background: Acute respiratory distress syndrome (ARDS) is life treating condition, with intensive general inflammation. Objective: Inflammation can be present with infection or without. Septic embolism, according to our previous experience, is more often multiple, than single. General hypoxia of hall body cause damage of all tissue, and generalinflammationintensifies. A vicious circle was formed and inflammation runs its course in what is very often irrelevant how it was begun.How often pulmonary embolism causes ARDS and what are the main features of this disease, is the goal of the study. Methods: Patients with ARDS, treated in pulmonary intensive care unit were analyzed. Chest X-ray, microbiological analysis of sputum or bronchoalveolar lavage specimen, chest CT scan, blood culture, CRP (mg/dl), deep-dimmer and blood cell count, were performed for all cases. Results: In three years period 53 patients with ARDS were treated. Out of all 19 with septic pulmonary embolism (14 multiple), (CRP 198±28). In only 12 patients origin of venous thrombus was found. Out of all 6 patients have massive non septic embolism (CRP 28±7), 18 heavy pneumonia (CRP 166±28), 4 with interstitial pneumonia (CRP 76±19), 5 with massive TB with caverns (CRP 35±13) and 6 with not well defined cause. Blood culture was positive in 14 cases with septic embolism and in 11 cases with pneumonia. CRP was elevated in all cases but highest was in septic embolism (Mann-Whitney test p=0,024). Conclusion: Septic pulmonary embolism was common cause of ARDS, mostly as multiple, and should be considered even if origin of thrombus was found or not.

R. Sejdinović, E. Jusufovic, D. Keser, B. Prnjavorac, Ljiljana Sejdinovic, Azra Okanović

New prognostic factor of lung cancer are being intensively studied currently. A small number of studies compare the importance of molecular makers with so far known functional and clinical prognostic factors. Purpose of this study was to find out whetherp16(ink4) expression is more superior prognostic factor in survival rates in non-small lung cancer (NSCLC) patients than spirometry tests. 100 NSCLC patients (50 squamous and 50 adenocarcinoma) with IIIB and IVA stage and 80 healthy individuals were included. p16(ink4) was immunohistochemicaly detected on formalin-fixed tissues. We measured s pirometry tests : vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), Tiffeneau index (FEV1/FVC ratio) and forced expiratory flow 25% to 75%. 2-year progression-free survival (PFS) and overall survival (OS) were observed. Low p16(ink4) expression and impared spirometry parameters correlated with worse 2-year survival outcomes, in both adenocarcinoma and squamous carcinoma. In squamous carcinoma p16(ink4) expression was an independent negative prognostic marker. Severe impairments of spirometry tests had similar prognostic value as low p16(ink4) expression in both NSCLC subtypes. In contrast to p16 (ink4) as a negative molecular prognostic factor, spirometry testings are widely achievable and affordable and could be serviceable prognostic marker in NSCLC patients in advanced NSCLC. Further studies including all clinical stages of NSCLC are needed.

AIM To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration, triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2. METHODS A prospective study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia: examined group (30 patients; 15 females and 15 males), and control group (30 patients; 12 females and 18 males). All were treated with metformin (850-1700 mg/day). Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks. Body mass index and concentrations of total cholesterol, triglycerides and glucose in serum were compared before and after the treatment. RESULTS The group treated with 600 mg alpha-lipoic acid lost significantly more weight, and had lower triglyceride level than the control group. There were no significant differences in total cholesterol and glucose serum levels between the groups. CONCLUSION Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2. It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2.

Growing body of evidence suggests that molecular markers are an important prognostic marker for non-small lung cancer (NSCLC). Using targeted therapy based on these markers leads to improved outcomes in lung adenocarcinoma. However, progress of targeted therapy in squamous lung cancer is still modest. p16(ink) protein acts as tumor suppressor and vascular endothelial growth factor (VEGF) promotes tumor angiogenesis. Purpose of this study was to evaluate the difference in p16(ink4) and VEGF expression between squamous and adenocarcinoma of the lung; to evaluate the relationship of p16(ink4) and VEGF expression to survival outcomes in NSCLC patients, and the difference of their prognostic values between squamous and adenocarcinoma subtypes. 100 NSCLC patients (50 squamous and 50 adenocarcinoma) and 80 healthy individuals were included. p16(ink4) and VEGF proteins were immunohistochemicaly detected on formalin-fixed tissues. One- and 2-year progression-free survival (PFS) and overall survival (OS) were observed. p16(ink4) expression was significantly lower in squamous type compared to adenocarcinoma. In both squamous and adenocarcinoma, high VEGF expression correlated with worse 1-year PFS and OS, but only with worse 2-year PFS. Low p16(ink4) expression correlated with worse 1- and 2-year PFS, as well as OS, in both NSCLC subtypes. In squamous lung cancer p16(ink4) expression was an independent negative prognostic marker. Our study confirms the difference of p16(ink4) protein expression in squamous and adenocarcinoma of the lung. Besides anti-VEGF therapy, the regulation of p16(ink4) expression could have a therapeutic potential in NSCLC, especially in squamous lung cancer.

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