AIMS: The aim of the study was to investigate the prognostic value of Ki-67 and histological grade in patients with estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative early breast cancer. Although the proliferation activity of different tumors assessed with antigen Ki-67 was extensively studied in the last decade and showed that Ki67 expression was a useful prognostic factor in breast cancer, there is still a controversy about the utility value of Ki-67. METHODS: The retrospective study covered the period from 2016 to 2022. Year included 106 patients from Brcko District, with early estrogen-positive and HER2 receptors-negative breast cancer. The average patients’ age was 62.37 ± 11.65 years. Patients were divided into groups with high/low Ki-67 and high/low histological grade. Multiple linear regression analysis was performed for disease relapse and mortality. RESULTS: Patients with high Ki-67 were more frequent postmenopausal, had higher histological grade, cancer ˂2 cm, more frequent lymph nodes’ metastases, more frequently underwent to axillary surgery, and had a higher mortality rate. Patients with high histological grade were older, more frequent postmenopausal, had more frequent metastases to the lymph nodes, more frequent occurrence of high Ki-67, more frequent relapse of disease, and more frequent of death. CONCLUSION: Combination of high Ki-67 with high histological grade in ER positive and HER2-negative early breast cancer is an important prognostic factor.

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.

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.

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.

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.