A Single-Center Experience on the Treatment Outcomes of Patients with COVID-19-Pleural Disorders: Lessons for the Future.

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.

Anemia of inflammation in patients with colorectal cancer: Correlation with interleukin-1, interleukin-33 and galectin-1.

Background: Patients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients. Methods: Concentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia). Results: CRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients. Conclusions: Predomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development.

IL 33 Correlates With COVID-19 Severity, Radiographic and Clinical Finding.

Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity. Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed. Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1ß, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1ß, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1ß, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1ß, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven. Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.

Increased Severity of Ulcerative Colitis in the Terminal Phase of the Metabolic Syndrome.

Ulcerative colitis is chronic immune-mediated disorder that affects primarily colonic mucosa. The metabolic syndrome has increasing global prevalence with a significant impact on biology of chronic diseases, such as ulcerative colitis. Today it is known that the metabolic syndrome attenuates severity of ulcerative colitis. Still, there is no evidence that different stages of metabolic syndrome alter the course of the ulcerative colitis. The aim of this study was to dissect out how progression of the metabolic syndrome impacted the biology of ulcerative colitis and severity of clinical presentation. Seventy-two patients (41 men and 31 women, 22-81 years old) were enrolled in this observational cross-sectional study. Concentrations of pro- and anti-inflammatory cytokines in serum and feces samples were measured and phenotype of colon infiltrating cells was analyzed. Patients in the terminal phase of the metabolic syndrome have clinically and pathohistologically more severe form of ulcerative colitis, which is followed by decreased concentrations of systemic galectin-1, increased values of systemic pro-inflammatory mediators and increased influx of lymphocytes in affected colon tissue. Our data suggest that reduced concentrations of galectin-1 and predomination of the pro-inflammatory mediators in patients with terminal stage of the metabolic syndrome enhance local chronic inflammatory response and subsequent tissue damage, and together point on important role of galectin-1 in immune response in ulcerative colitis patients with the metabolic syndrome.

DNMT1 and DNMT3B genetic polymorphisms affect the clinical course and outcome of melanoma patients.

The aberrant DNA methylation plays a critical role in a number of different malignancies, including melanoma. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), involved in methylation maintenance (DNMT1) and de novo DNA methylation (DNMT3A and DNMT3B). The current study investigated the association of genetic variants in the DNMT1 and DNMT3B with the clinicopathologic features and the clinical course of melanoma patients. In the present study, DNMT1 (rs2228612, rs2228611, and rs2114724) and DNMT3B (rs406193 and rs2424932) polymorphisms were examined in 123 melanoma patients. Single nucleotide polymorphisms were assessed using TaqMan SNPs Genotyping Assays according to the manufacturer's protocols. The carriers of the variant genotype of DNMT1 rs2228612 had poorer overall survival and recurrence-free survival, (P = 0.000 and 0.000, respectively), and an increased risk for adverse outcome [hazard ratio (HR) = 6.620, 95% confidence interval (CI): 2.214-19.791, P = 0.001]. DNMT1 rs2228612 was also associated with ulceration (P = 0.045), nodal status (P = 0.030), progression (P = 0. 007), and stage of disease (P = 0.003). Univariate analysis indicated that tumor-infiltrating lymphocytes could be a marker of good prognosis in melanoma patients (HR = 0.323, 95% CI: 0.127-0.855, P = 0.025), whereas the genotype distribution of the DNMT3B rs406193 polymorphism correlated significantly with the presence of tumor-infiltrating lymphocytes (P = 0.012). The multivariate analysis showed that the DNMT1 rs2228612 polymorphism (HR = 12.126, 95% CI: 2.345-62.715, P = 0.003) is an independent predictor of poor overall survival in melanoma patients. As expected, disease progression was also found to be an independent prognostic factor in melanoma patients (HR = 37.888, 95% CI: 3.615-397.062, P = 0.002). DNMT1 rs2228612 was found to be an independent predictor of poor overall survival in melanoma patients. DNMTs polymorphisms could serve as a potential target for novel therapeutic approaches.

Comparison of Efficiency of Pleurodesis Between Video Assisted Thoracoscopic Surgery (VATS) and Standard Thoracostomy.

BACKGROUND: Chemical pleurodesis is generally accepted palliative dyspnea therapy and preventive of re-accumulation of pleural fluid in patients with malignant pleural effusions. AIM: Comparative analyses of efficiency of chemical pleurodesis between Video Assisted Thoracoscopic Surgery (VATS) and standard thoracostomy. METHODS: From 01.01.2016-01.01.2017 at the Clinic for Thoracic Surgery of University Clinical Center (UCC) Sarajevo retrospective analysis was performed. Studied patients underwent VATS pleurodesis (G1) and standard thoracostomy pleurodesis (G2), with 60 in each group, respecting defined inclusion and exclusion criteria. Pleurodesis success was examined radiologically over the next three months. RESULTS: Average age of all patients was 63.97±8.75 years. Gender related, 45% were men and 55% were women (F/M=1.47:1). Average hospitalization was 7.22±1.37 (G1: 6.68±1.16; G2: 7.44±1.40; Mann-Whitney U-test: p=0.0016) days. Average thoracic drainage duration was 5.45±1.69, (G1: 4.28±1.15,G2: 6.05±1.58; Mann-Whitney U-test p<0.0001) days. Pleurodesis success after first month was 98.30% in G1, 91.60% in G2 (G1 vs. G2; p=0.2089); after second month was 98.30% in G1, 78.30% in G2 (G1 vs. G2; p=0.0011) and after three months was 91.60% in G1, 63.30% in G2(G1 vs. G2; p=0.0006). Average dyspnea degree (0-5) after the pleurodesis was 0.050±0.22 in G1 and 0.62±0.76 in G2 (Mann-Whitney U-test; p=0.0001). Complication were noticed in 9.2% patients, in G1 3.3%, 15.0% in G2. CONCLUSION: Difference in pleurodesis efficiency between the G1 and G2 was established after second month and was even more evident after third month in favor of G1. Results show the significant statistical improvement of the degree of dyspnea in G1 as opposite to the G2.

Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma.

BACKGROUND AND OBJECTIVES: The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. METHODS: Concentrations of galectin-3, TNF-α, TGF-ß, IL-10, and IL-1ß were analyzed in samples of blood and stool of 60 patients with CRC. RESULTS: Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-ß and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. CONCLUSIONS: Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.

Examination of Risk Factors for the Development of Surgical Site Infections.

INTRODUCTION: Hospital-acquired infections (HAI) and surgical site infections (SSI) are a global public health problem. The aim of the study was to determine the incidence of SSIs at the Surgical Clinics of the University Clinical Centre Banja Luka and to identify risk factors for the development of SSIs. METHODS: In order to determine the frequency of SSIs through the incidence compared to the patients operated at the Surgical Clinics of the University Clinical Centre Banja Luka, we conducted a prospective cohort study which encompassed 11.216 operated patients, in the period from November 11th, 2014 to September 30th, 2015. In order to identify risk factors for the development of SSIs, a nested case-control study of risk factors for SSIs was conducted. The study group consisted of patients who were diagnosed with SSIs in the period of monitoring, while the control group was consisted of patients without SSIs who corresponded with the study group in age and sex. RESULTS: The highest values of incidence of SSIs were observed at the Department of Anesthesia and Intensive Care (2.65%), Department of Orthopaedic Surgery (2.48%) and the Department of Vascular Surgery (2.15%), and the lowest ones at the Department of Urology (0.59%). Among the cases of SSIs, deep infections of the surgical site were the most represented (82.7%). Multivariate logistic regression was used to identify the following independent risk factors: length of pore-operative stay in hospital (p=0.000; OR=1.062; 95% CI=1.037-1.087), reintervention (p=0.000; OR=22.409; 95% CI=6.361-79.071) and cotrticosteroids (p=0.023; OR=4.141; 95%CI=1.221-14.047). CONCLUSION: The incidence of SSIs at the Surgical Clinics of the University Clinical Centre Banja Luka is at the level of hospitals in developed countries. There are a number of risk factors for SSIs, which may be prevented.

Potential Hepatoprotective Role of Galectin-3 during HCV Infection in End-Stage Renal Disease Patients.

Hepatitis C virus infection (HCV), one of the greatest causes of liver disease, is a frequent complication in patients with end-stage renal disease (ESRD) on dialysis. ESRD is defined as decreased glomerular filtration and also accompanied by impaired function of the immune system. Galectin-3 is a ß-galactoside-binding lectin, involved in various biological processes including pathogenesis of chronic renal disease. The aim of our study was to estimate disease severity in ESRD HCV+ patients and analyze the serum concentrations of IL-1ß, IL-4, IL-23, and IL-6; anti-HCV antibodies; and galectin-3. Also, we attempted to determine potential correlation between galectin-3 level and parameters of disease severity ALT and AST. Our results showed decreased levels of ALT and AST (p = 0.00), demonstrating less liver destruction in ESRD HCV+ patients in comparison to HCV+ patients. Increased levels of IL-6 (p = 0.03) implicate a hepatoprotective role of IL-6 in these patients. Also, level of galectin-3 (p = 0.00) in the serum of ESRD HCV+ patients was higher than that of HCV+ patients. This alteration was accompanied with negative correlation between galectin-3 and AST and ALT, respectively (p = 0.029; p = 0.033). The presence of increased systemic levels of IL-6 and Gal-3 in ESRD HCV+ patients may be an attempt to counteract or limit ongoing proinflammatory processes and to downregulate chronic inflammation, suggesting the new aspects of HCV infection in ESRD patients.

High prevalence of risk factors for chronic kidney disease in Balkan endemic nephropathy foci.

BACKGROUND/AIMS: The aim of this study was to find out the prevalence of the most frequent risk factors for chronic kidney disease (CKD) and the prevalence of urinary abnormalities in adult inhabitants of three Balkan endemic nephropathy (BEN) villages near Bijeljina, Bosnia and Herzegovina. METHODS: The survey consisted of an interview, blood pressure measurement, and urine dipstick test for proteinuria, hematuria, and glycosuria. RESULTS: The study involved 1625 (739 males, aged 51 ± 16 years) subjects: 319 (19.6%) with positive family history for BEN, 585 (36%) with hypertension, 604 (37.2%) above 60 years, 146 (9%) with diabetes, and 566 (34.8%) with none of these risk factors. Proteinuria was present in 6.2-7.1% of the subjects with risk factors for CKD but in 3.4% of those without risk factors. Systolic blood pressure and BEN in brother/sister were found to be significant variables associated with proteinuria, but female gender and history of kidney disease with hematuria. CONCLUSION: In addition to a family burden for BEN, other risk factors for CKD were highly prevalent in BEN villages of the Bijeljina municipality. The frequency of proteinuria was higher in the at-risk group than in the group without risk factors and increased with the number of risk factors.