Objective To evaluate the systemic immune-inflammation (SII) index in patients with rheumatoid arthritis (RA) stratified by systemic inflammatory status. Methods Seropositive patients with RA (n=58) were divided into two groups based on serum hs-C-reactive protein (hs-CRP) levels: RA patients with hs-CRP levels of at or 3 mg/L or above (high systemic inflammatory status; n=38) and RA patients with hs-CRP levels of less than 3 mg/L (low systemic inflammatory status; n=20). The control group comprised 31 healthy individuals. Blood samples were tested for the next parameters: leukocytes, neutrophilic granulocytes, lymphocytes, thrombocytes [platelet (PLT)], high-sensitivity hs-CRP, sed rate [erythrocyte sedimentation rate (ESR)], neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). The SII index was derived as Neu x PLT/Lym. Results In patients with RA, the SII index was elevated compared with that of healthy individuals and positively correlated with hs-CRP, erythrocyte sedimentation rate, NLR, MLR, PLR, tender joint count, and swollen-to-tender joint count ratio. Patients with RA who had hs-CRP levels of 3 mg/L above exhibited a statistically significant increase in the SII compared with those with hs-CRP levels below 3 mg/L. Additionally, within the cohort of RA patients with hs-CRP levels at or above 3 mg/L, a positive correlation was found between the SII index and both NLR and PLR. The SII index was positively correlated with NLR, MLR, and PLR in RA patients with hs-CRP levels below 3 mg/L. The cut-off point of the SII index for distinguishing between RA cases with hs-CRP levels 3 mg/L and those with hs-CRP levels 3 mg/L or higher was ≥323.4, with a sensitivity of 77.6% and a specificity of 54.8%. Conclusions The serum SII index can be a potentially useful marker for evaluating the inflammatory process and clinical progression of RA.

BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in Bosnia and Herzegovina. Elevated LDL-cholesterol is established as a strong marker of cardiovascular risk. Some researchers believe that measuring triglyceride levels gives a good assessment of the residual risk for ASCVD besides the measurement of LDL-cholesterol. OBJECTIVE: The aim of this study was to evaluate the overall prevalence of major risk factors for ASCVD, lipid profile and 10-year fatal cardiovascular risk using the HeartSCORE scoring system. Further, we want to evaluate the prevalence and relationship between elevated triglyceride levels and high 10-year fatal cardiovascular risk calculated as a HeartSCORE. METHODS: This is a cross-sectional study conducted on 832 volunteers aged between 40 and 65 years without a diagnosis of diabetes and without known preexisting cardiovascular disease, as a part of the preventive program conducted at the Family Medicine office. Data were collected for ASCVD risk factors and lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides). 10-year fatal cardiovascular risk was calculated using the HeartSCORE scoring system for countries with high CV risk. RESULTS: Among 832 participants included, 565 (67.9%) were female, and 267 (32.1%) were male. We found high prevalence of hypertension (27.7%), obesity (32.2%), and smoking (36.2%). All lipid parameters, except HDL-C, were not optimal. Only 17.4% of participants had normal estimated HeartSCORE risk, while more than one-third (33.9%) had high or very high estimated HeartSCORE risk. Although we found a higher percentage of participants with elevated triglycerides in groups with higher HeartSCORE, there was a very weak positive correlation between values of triglycerides and the 10-year risk of a fatal cardiovascular event ( r = 0.249, p = 0.000). CONCLUSION: The high prevalence of major known risk factors and high estimated HeartSCORE risk indicate a high overall risk for ASCVD in the sample. The proportion of participants with elevated triglycerides was increased in patients with high HeartSCORE risk what implicates importance of triglyceride measurement.

Background: Pleural disorders in novel coronavirus disease 2019 (COVID-19), responsible for the deaths of more than 6.7 million people worldwide, are relatively uncommon and underappreciated findings. The severity of the pleural disease in these patients correlates with the treatment outcome and overall prognosis. Objective: We aim to review our experience with treatment modalities and prognosis in 45 patients with COVID-19, who were treated at our Clinic between April 2020 and October 2021. Methods: We conducted a retrospective, single-center, cross-sectional study. Demographic data, the type of thoracosurgical intervention(s), and treatment outcome for 45 patients included in this study were recorded for every patient. We analyzed the type and number of treatment modalities according to the pleural disorder, and the outcome of the treatment. Results: Pneumothorax was the most common COVID-19-related pleural disorder, followed by the pleural effusion. Tube thoracostomy was the mainstay of treatment, performed in 84.4% of patients with unilateral pleural complications. In total, 20% of our patients were on mechanical ventilation, and all of them had a fatal outcome. We found statistical significance in comparison to the percentage of fatal outcomes between patients treated with and without mechanical ventilation (p=0.000). Conclusion: COVID-19-related pleural disorders are prognostic markers of disease progression. Mechanically ventilated patients who require tube thoracostomy have an unfavorable prognosis.

Introduction: Pleural complications in coronavirus disease 2019 (COVID-19) are relatively uncommon findings. Pleural involvement in these patients may directly correlate to disease severity and overall prognosis. We aimed to review clinical features and treatment approaches for pleural complications (accumulation of fluid/air inside the pleural cavity) in 45 patients with COVID-19, who were treated at our institution between April 2020 and October 2021. Methods: Our study was designed as single-center, observational, cross-sectional study of 45 patients with COVID-19 and at least one radiologically verified pleural complication. Demographic data, radiological findings, as well as type and number of thoracosurgical intervention(s) were recorded for every patient. We included patients of both genders and various age groups, with positive RT-PCR assay for COVID-19 and radiologic features of pleural complications, which required single or multiple thoracosurgical interventions. Results: Unilateral pleural complications were more common, right-sided pleural complications were found in 44.4% of patients. Right-sided pneumothorax was reported in 26.7% of patients. Almost one-fourth of our patients required invasive mechanical ventilation. Tube thoracostomy was performed in 84.4% of patients with unilateral pleural complications. A fatal outcome was most common in patients over 60 years old. More than half of patients with bilateral pleural complications died in our study. Conclusions: Pleural complications are a rare finding in patients with COVID-19. Tube thoracostomy is the mainstay of treatment for most symptomatic patients with pleural complications. Future research should be directed toward investigation of long-term pulmonary consequences in patients with COVID-19.

Abstract Background: Low-grade chronic inflammation is an important feature of chronic kidney disease (CKD). Aim: To determine the values of C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with different stages of CKD and to examine how they change depending on the progression of renal damage. Materials and methods: A cross-sectional descriptive comparative study included 157 subjects at different stages of CKD which was assessed based on glomerular filtration rate (GFR) calculated according to the MDRD equation. CRP was analyzed by an immunoturbidimetric method. NLR and PLR were calculated by a mathematical calculation after a blood count was performed. Results: The present study showed an increase in serum creatinine, CRP, and NLR values with progression of renal failure. There was a statistically significant difference in the creatinine and CRP concentrations between groups with different stages of CKD (p <0.001 for all comparisons). A significant positive correlation was found between NLR and CRP, while negative, significant correlations were observed between NLR and eGFR as well as between PLR and eGFR. There was a slight increase in PLR value with the progression of renal impairment, but the correlation between PLR and CRP was not significant. Conclusion: These results suggest that NLR, together with CRP, may serve as an indicator of systemic low-grade inflammation progression in patients with CKD. Larger prospective studies are required to observe the possibility of using NLR as a surrogate marker for CRP in patients with CKD.

Echinococcus multilocularis has been spreading through Central Eastern Europe but has not yet been reported in Bosnia and Herzegovina (B&H). Recently, this parasite is confirmed in Croatia suggesting the movement of the parasite's distribution limit further south. Given that there is no surveillance or monitoring system for echinococcosis in B&H, our study was designed as a pilot study of E. multilocularis. A total of 57 red foxes originating from 24 localities all over the country were collected during the routine rabies monitoring, autopsied and examined for the presence of echinococcosis. Based on intestinal scraping technique and microscopy, E. multilocularis adult worms have been detected in one (1/57, 1.75%) red fox. To verify this finding and to differentiate Echinococcus spp., DNA extracted from adult worms was subjected to species-specific PCR targeting part of the mitochondrial 12S ribosomal RNA gene. E. multilocularis PCR-positive samples were further confirmed by NGS sequencing of a 203 bp amplified fragment of 12S rRNA, which has been deposited in GenBank (Accession no.: OP047920). This finding represents the first detection of E. multilocularis in B&H, strongly suggesting its presence in the country. The confirmation of the parasite in the same locality where migrants/refugees temporarily stay on their route to Western Europe highlights the need for a One Health approach in addressing all future questions. Moreover, the first detection of E. multilocularis in B&H warrants the need for the implementation of an appropriate state surveillance program.

Abstract Background Accumulated evidence on risk factors for adverse COVID-19 outcomes revealed that old age and male sex are main associates, next to pre-existing comorbidities, as analysed from scattered single cohorts of hospitalised COVID-19 patients of accessible electronic medical records. Hence, evidence from federated analyses is called for to provide a more comprehensive and robust analyses of risk factors. Methods Using the unCoVer network, i.e., a research platform of 29 partners for the expert use of patient data as routinely gathered in real-world healthcare settings, present analyses restricted to available data of four hospitals from Spain, Slovakia, Romania and Bosnia and Herzegovina covering 8,287 hospitalised COVID-19 patients. In-hospital death after COVID-19 diagnosis was examined in relation to common pre-existing comorbidities using virtual pooling of logistic regression models adjusted for age and sex. Results Patients were on average 60.1 (± 20.9) years, 50.7% were male, almost half (43.3%) had at least one pre-existing comorbidity (17.4% having obesity, 21.9% hypertension, 18.0% diabetes and 13.7% cardiovascular diseases (CVD)), and 12.6% died during hospitalisation. Patients with comorbidities had a higher risk of mortality that was increasing with the number of comorbidities: from a virtual pooled odds ratio of 1.16 (95%CI: 0.96, 1.40) for one vs none to 1.30 (1.04, 1.64) and 2.14 (1.64, 2.79) for two and three or more comorbidities, respectively. Of the comorbidities, highest risk was seen for CVD (1.68; 1.40, 2.01), followed by hypertension (1.40; 1.19, 1.64) and diabetes (1.27; 1.07, 1.50), and the lowest for obesity (1.13; 0.94, 1.37). Conclusions By federated analyses, this study confirmed that the number of comorbidities was a strong risk factor for in-hospital death after COVID-19, in particular CVD. The unCoVer platform pursues using scattered data sources by innovative computational resources and integrated information for enhanced impact. Key messages Federated analyses, capable of streamlining ethical and legal aspects, provide unique opportunities for robust results to inform public health. Higher COVID-19 in-hospital mortality risk with increasing number of comorbidities.

Introduction unCoVer—Unravelling data for rapid evidence-based response to COVID-19—is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving pandemic. Methods and analysis From the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients’ baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often excluded. Ethics and dissemination After strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer’s activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference communications.

Introduction Cytokines exert biological function through signal transducer and activator of transcription factors. Prostaglandins have function as promotors, where play a key role in generation of the inflammatory response and as ones that solve inflammatory process. Non-steroidal anti-inflammatory drugs, inhibit prostaglandin synthesis but the existence of additional mechanisms is present. Thus, we aimed to explore effects of topically applied NSAIDs on the levels of PGE2 and Stat3 in the setting of two in vivo induced acute inflammation models. Methods Male Wistar rats were randomized into five equal groups: 4 treated and a control group. Diclofenac or ketoprofen patches were applied in two different doses, i.e. equivalent to human therapeutic dose, and three times higher dose. Three hours later either model of inflammation (with 20% yeast, or with 1% carrageenan) was induced. Blood samples were taken 3 hours after and concentration levels of PGE 2 and Stat3 were determined using ELISA. Body temperature was measured at 0. 1st, 3rd and 5th hour after inflammation induction and presented in Celsius degrees. Shapiro-Wilk, Leven’s, Welch’s One-Way ANOVA, Kruskal-Wallis test and adjustment by Bonferroni correction were applied. Results In both inflammation models, no differences in the mean values of PGE 2 between control, low and high dose groups treated by either diclofenac or ketoprofen were found. In yeast inflammation, the mean value of Stat3 was significantly higher in both dose ketoprofen groups compared to control group. After ketoprofen application, no significant differences in body temperature between groups at hour 0 and 5 in either model of inflammation induced, while at 1st hour after carrageenan inflammation, significant differences were found with significantly higher values in low dose ketoprofen group compared to control group. In yeast application, significant differences in body temperature were found at hour 3 after inducing inflammation and post hoc pairwise comparison test revealed significant higher values in low dose ketoprofen group compared to control. Conclusion Elevated Stat3 values post ketoprofen application in yeast model of induced inflammation were detected. Further investigation of cytokine microenvironment as well as the mechanisms of ketoprofen influence on inflammation are needed.