Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other malignant tumors. In this review, we discuss the published results regarding CAR T cell therapy of CLL, possible mechanisms of failures and expected developments.

Background/Objectives: The assessment of platelet kinetics (APK) is recommended for patients with chronic idiopathic thrombocytopenic purpura (chITP). The aim of this study was to examine the importance of APK as a prognostic instrument in the selection of therapy in children with chITP. Methods: Retrospective, observational research, which included chITP children who were treated and subjected to APK in Serbia for 25 years (total number was 152). Results: In the acute phase of the disease, 15% of patients had life-threatening bleeding, 15% were asymptomatic, and there were no cases of fatal bleeding. Mean platelet life was 0.89 ± 0.47 days. A total of 45% of patients had normal platelet production, and 35% had very low production. Among the patients, 55% exhibited splenic platelet sequestration, 35% had mixed sequestration, and 10% showed hepatic platelet sequestration. Platelet lifespan and production indices were less reliable parameters, due to numerous contradictory results, especially when compared with the location of platelet sequestration. Distribution of bleeding and therapy-resistant patients was dominant with mixed sequestration. Good therapy responders had dominant splenic sequestration. In the chronic phase of the disease, initial therapy was sufficient for 40–45% of patients, while another 25% required second-line therapy, regardless of platelet sequestration location. A total of 25% percent of patients had undergone splenectomy, and all of them were in stable remission. The remaining 10%, which represented the most severe cases, required all available therapies, had equally mixed and liver sequestration, and splenectomy showed no effect. Conclusions: APK may be a determining factor for the selection of splenectomy as a therapeutic option in case of predominantly splenic sequestration. Although the platelet production index has been explored in several studies, its clinical relevance remains controversial. In our findings, it did not contribute to therapeutic decision-making and may even lead to misinterpretation. The factors distinguishing the minority of bleeding and therapy-resistant patients with similar laboratory profiles remain unclear.

Background: The newly synthesized palladium(II) complex [Pd(L1)Cl]Cl (where L1 = N²,N⁶-bis(5-methylhthiazol-2-yl)pyridine-2,6-dicarboxamide) has demonstrated significant in vitro antitumor activity. In this study, the effects of this complex on the immune response and its antimicrobial potential were evaluated. Methods: Splenocytes isolated from mice were treated with lipopolysaccharide (LPS)/Concanavalin A (ConA) along with the Pd(II) complex. The concentrations of IFN-γ, IL-17, IL-4, TNF-α, IL-1β, and IL-10 were measured using commercial ELISA kits. The antimicrobial effect was tested against reference strains of Gram-positive and Gram-negative bacteria, as well as yeast. The Minimal Inhibitory Concentration (MIC) was determined via the broth microdilution method, followed by the determination of Minimal Bactericidal/Fungicidal concentrations (MBC/MFC). Results: The Pd(II) complex induced an increase in the concentration of all tested cytokines compared to untreated cells. Co-treatment with Pd(II) complex and LPS significantly increased the levels of IFN-γ, IL-1β, and IL-17 compared to the LPS-only-stimulated group. Co-treatment with ConA and the Pd(II) complex resulted in a significant increase in TNF-α and IL-17 levels, whereas a significant decrease was observed in the concentrations of IL-10, IL-4, and IFN-γ compared to the ConA-only-stimulated group. The tested complex showed weak to moderate antimicrobial activity, Gram-positive bacteria showed better susceptibility to the examined complex compared to Gram-negative. Conclusions: Results of the study indicate that the Pd(II) complex exhibits a significant immunomodulatory effect on splenocytes, alongside weak to moderate antimicrobial activity.

Surgical treatment and formation of a stoma can be lifesaving for colorectal cancer patients. However, the quality of life is often impaired in patients with stoma. The goal of this study is to determine the quality of life of patients with stoma and cancer, and the relationship between the quality of life and characteristics of these patients.The study was conducted from 2018 to 2020 and included a total of 64 patients of both sexes with colorectal cancer and temporary or permanent stoma. The European Organization for Research and Treatment of Cancer with Quality of Life Questionnaire (EORTC QLQC29-30) and the anonymous WHO Quality of Life Questionnaire SF-36 were used for self-assessment of quality of life.Our study included 39 (61.0%) men and 25 (39.0%) women. 24 patients (37.5%) had colostomy, 14 patients (21.9%) had ileostomy, and 26 patients (40.6%) underwent surgery for resection of colorectal cancer without stoma. A significant number of women were in the group of patients with a permanent stoma (p = 0.01). There was no statistically significant difference in the assessment of general health (p = 0.680) and quality of life (p = 0.721) during the past month in relation to gender. Patients without a stoma rated their general health better compared to those with stoma and the difference reached statistical significance (p = 0.035). There was no statistically significant difference in the assessment of quality of life between the group of patients with stoma and without stoma, as well as between the patients of different age groups.Patients with stoma rated their general health as worse, but not their quality of life.

Background: There are challenges that require collaboration among researchers to ensure that tobacco harm reduction strategies are evidence-based. One key challenge is evaluating the safety of flavors used in electronic cigarettes (e-cigarettes). While many flavorings are approved as food additives or deemed “generally recognized as safe” (GRAS) for ingestion, this does not guarantee their safety when inhaled. In this context, the international research group Replica replicated a study conducted by Fetterman and colleagues in 2018, investigating the effects of aerosolized vanillin - one of the most popular flavors in vaping - on vascular endothelium when vaporized by an electronic cigarette. Methods: We used Aspire Zelos 3 e-cigarette and prepared e-liquids containing propylene glycol, vegetable glycerin and vanillin. The e-liquids were vaporized under two settings - regular (1 ohm coil using wattage control mode at 14 watts) and sub-ohm (0.3 ohm coil using temperature control mode at 200 °C) – using a vaping machine, following the standardized puffing regime, ISO20768:2018. The vapor was then collected into a trapping solution to prepare aqueous extracts for the treatment of human aortic endothelial cells. We evaluated cytotoxicity, oxidative stress, nitric oxide bioavailability, and inflammation addressing some gaps reported in the original study. Results: We observed some harmful effects, mostly attributable to ethanol, used to dilute vanillin in the original work by Fetterman, but no harmful effects on cell viability, their ability to produce nitric oxide, or oxidative stress from vanillin. Furthermore, no pro-inflammatory effects of vanillin were observed in terms of ICAM-1 and IL-6 gene expression. Conclusions: Our results confirm the endothelial cell dysfunction observed in the original paper, but clarify that these effects are mainly attributable to ethanol and not to vaporized vanillin. These findings suggest that vanillin could be a safer flavoring agent for e-cigarette, without causing adverse effects on the cardiovascular system.

Background/Aim. Prevalence studies, also known as cross-sectional studies, offer an effective approach for gathering high-quality data on particular health concerns. The aim of the study was to analyze the utilization of antimicrobial medications (AM) in a tertiary healthcare institution. Methods. A prevalence study on AM use was performed at the University Clinical Center Kragujevac, Serbia, in early November 2022. This research was conducted as part of the Fifth National Research Initiative and employed the standardized methodology established by the European Center for Disease Prevention and Control (ECDC). Data was collected on all patients admitted to the ward before 8 a.m. Results. Among the 567 patients included in the study, 246 received at least one AM, yielding a prevalence rate of 43.4% (95% confidence interval: 39.3-47.6). The most common indications for AM use were community-acquired infections (54.9%), followed by healthcare-associated infections (19.1%), surgical prophylaxis (20.7%), and medical prophylaxis (3.7%). Parenteral administration was the most common route for AM ad-ministration (89.6%). In 97.6% of cases, the rationale for the drug application was documented in the patient?s medical records. Third-generation cephalosporins were the most frequently utilized antimicrobial group, comprising 17.9% of usage, followed by carbapenems at 12.7%, glycopeptides also at 12.7%, and fluoroquinolones at 11.8%. According to the Access-Watch-Reserve (AWaRe) classification, antibiotics under supervision were prescribed most frequently (66.4%), followed by first-choice antibiotics (28.1%), with reserve antibiotics comprising 5.5%. Conclusion. The implementation of measures to regulate the use of AM is required to retain the efficacy of these medications in the future.