The possible cardioprotective effects of translocator protein (TSPO) modulation with its ligand 4′-Chlorodiazepam (4′-ClDzp) in isoprenaline (ISO)-induced rat myocardial infarction (MI) were evaluated, alone or in the presence of L-NAME. Wistar albino male rats (b.w. 200–250 g, age 6–8 weeks) were divided into 4 groups (10 per group, total number N = 40), and certain substances were applied: 1. ISO 85 mg/kg b.w. (twice), 2. ISO 85 mg/kg b.w. (twice) + L-NAME 50 mg/kg b.w., 3. ISO 85 mg/kg b.w. (twice) + 4′-ClDzp 0.5 mg/kg b.w., 4. ISO 85 mg/kg b.w. (twice) + 4′-ClDzp 0.5 mg/kg b.w. + L-NAME 50 mg/kg b.w. Blood and cardiac tissue were sampled for myocardial injury and other biochemical markers, cardiac oxidative stress, and for histopathological evaluation. The reduction of serum levels of high-sensitive cardiac troponin T hs cTnT and tumor necrosis factor alpha (TNF-α), then significantly decreased levels of serum homocysteine Hcy, urea, and creatinine, and decreased levels of myocardial injury enzymes activities superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as lower grades of cardiac ischemic changes were demonstrated in ISO-induced MI treated with 4′-ClDzp. It has been detected that co-treatment with 4′-ClDzp + L-NAME changed the number of registered parameters in comparison to 4′-ClDzp group, indicating that NO (nitric oxide) should be important in the effects of 4′-ClDzp.

Background: The aims of this paper are to examine the impact of the COVID-19 pandemic on the non-rational use of antibiotics and potential alterations in the antibiotic resistance profiles of multi-drug resistant (MDR) isolates of Klebsiella pneumoniae (KPN), Pseudomonas aeruginosa (PAE), and Acinetobacter baumannii (ABA). Material and Methods: This study was conducted at the tertiary University Hospital “Dr Dragisa Misovic-Dedinje” (Belgrade, Serbia) and was divided into three periods: pre-pandemic (1.4.2019–31.3.2020, period I), COVID-19 pandemic (1.4.2020–31.3.2021, period II), and COVID-19 pandemic-second phase (1.4.2021–31.3.2022, period III). Cultures were taken from each patient with clinically suspected infection (symptoms, biochemical markers of infection). All departments of the hospital were included in this study. Based on the source, all microbiological specimens were divided into 1° blood, 2° respiratory tract (tracheal aspirate, bronchoalveolar lavage fluid, throat, sputum), 3° central-line catheter, 4° urine, 5° urinary catheter, 6° skin and soft tissue, and 6° other (peritoneal fluid, drainage sample, bioptate, bile, incisions, fistulas, and abscesses). After the isolation of bacterial strains from the samples, an antibiotic sensitivity test was performed for each individual isolate with the automated Vitek^® 2 COMPACT. Antibiotic consumption testing was performed by the WHO guideline equations (ATC/DDD). Results: A total of 2196 strains of KPN, PAE, and ABA from 41,144 hospitalized patients were isolated (23.6% of the number of total isolates). The number of ABA isolates statistically increased (p = 0.021), while the number of PAE isolates statistically decreased (p = 0.003) during the pandemic. An increase in the percentage of MDR strains was observed for KPN (p = 0.028) and PAE (p = 0.027). There has been an increase in the antibiotic resistance of KPN for piperacillin–tazobactam, the third and fourth generations of cephalosporins (ceftriaxone, ceftazidime, and cefepime), all carbapanems (imipenem, meropenem, and ertapenem), and levofloxacin; of PAE for imipenem; and of ABA for amikacin. Total antibiotic consumption increased (from 755 DBD to 1300 DBD, +72%), especially in the watch and reserve group of antibiotics. The highest increases were noted for vancomycin, levofloxacin, azithromycin, and meropenem. MV positively correlated with the increased occurrence of MDR KPN (r = 0.35, p = 0.009) and MDR PAE (r = 0.43, p = 0.009) but not for MDR ABA (r = 0.09, p = 0.614). There has been a statistically significant increase in the Candida sp. isolates, but the prevalence of Clostridium difficile infection remained unchanged. Conclusions: The COVID-19 pandemic has influenced the increase in total and MDR strains of KPN, ABA, and PAE and worsened their antibiotic resistance profiles. An increase in the consumption of both total and specific antibiotics was observed, mostly of fluoroquinolones and carbapenems. A positive correlation between the number of patients on MV and an increase in MDR KPN and MDR PAE strains was noted. It is necessary to adopt and demand the implementation of appropriate antimicrobial stewardship interventions to decrease the resistance of intrahospital pathogens to antibiotics.

Endothelial dysfunction (characterized by reduced vasodilation or vasoconstriction, oxidative stress, inflammation, and pro-thrombotic condition) is a critical factor in the pathophysiology of various cardiovascular conditions, and the application of anesthetics can affect this dysfunction. Patients undergoing major surgery, especially cardiovascular surgery, are at increased risk of endothelial dysfunction. The impact of anesthetics on endothelial function can vary depending on the specific agent, dosage, duration of exposure, comorbidities, etc. Certain anesthetics, especially at higher doses, may increase the production of reactive oxygen species (ROS), leading to oxidative stress and endothelial dysfunction through reduced nitric oxid (NO) availability. Some anesthetics can modulate inflammatory responses, either by suppressing or exacerbating inflammation, or may affect the permeability of the endothelium, potentially leading to pulmonary edema and disruption of the blood-brain barrier. Anesthetics can influence endothelial glycocalyx. Understanding anesthetics effects is crucial for optimizing anesthetic management, particularly in patients with pre-existing cardiovascular issues. Therefore, the aim of this review is to critically evaluate the effects of different classes of anesthetics on endothelial function and oxidative stress. Specifically, we address how anesthetics influence NO bioavailability, endothelial glycocalyx integrity, inflammatory and oxidative pathways, and clinical outcomes in surgical patients. By summarizing current evidence, we aim to highlight mechanistic insights and identify potential perioperative strategies to minimize endothelial dysfunction.

Background: Patients with acute pancreatitis develop numerous complications and organ damage due to increased intra-abdominal pressure (IAP). These extrapancreatic complications determine the clinical outcome of the disease. Materials and methods: A total of 100 patients with acute pancreatitis were included in the prospective cohort study. Observed patients were divided into two groups according to their mean values of IAP (normal IAP values and elevated IAP values), which were compared with examined variables. Patients with intra-abdominal hypertension (IAH) were divided into four groups by IAP values, and those groups of patients were also compared with the examined variables. Results: Differences between body mass index (BMI) (p = 0.001), lactates (p = 0.006), and the Sequential Organ Failure Assessment (SOFA) score (p = 0.001) were statistically significant within all examined IAH groups. Differences between the mean arterial pressure (MAP) (p = 0.012) and filtration gradient (FG) (p < 0.001) were statistically significant between the first and second IAH groups in relation to the fourth. Differences in diuresis per hour (p = 0.022) showed statistical significance in relation to the first and third groups of IAH patients. Conclusions: Changes in IAP values lead to changes in basic vital parameters MAP, APP, FG, diuresis per hour, and lactate levels in patients with acute pancreatitis. Early recognition of changes in the SOFA score accompanying an increase in the IAP value is essential.

Personalized anesthesia has emerged as a key direction in modern perioperative medicine, driven by advances in molecular biology, analytical technologies, and digital monitoring. Traditional physiological parameters often fail to detect early stages of organ dysfunction, whereas molecular biomarkers provide earlier and more sensitive insight into inflammation, oxidative stress, neurotoxicity, and renal or hepatic injury. Inflammatory markers such as IL-6, CRP, and PCT indicate early immune activation, while oxidative stress biomarkers, including 8-isoprostanes and malondialdehyde, quantify metabolic imbalance and ischemia–reperfusion injury. Neurotoxicity biomarkers such as S100β, NSE, and GFAP allow early detection of subclinical cerebral injury, whereas kynurenine-pathway metabolites reflect neuroinflammation and the risk of postoperative cognitive dysfunction. Renal biomarkers such as NGAL, KIM-1, and cystatin C detect acute kidney injury significantly earlier than creatinine, and miR-122 holds strong potential as an early marker of hepatocellular injury. Genetic and epigenetic biomarkers—including polymorphisms in CYP2D6, CYP3A4/5, RYR1, OPRM1, and COMT, as well as microRNA-based signatures—enable individualized drug dosing and optimization of anesthetic strategies. Meanwhile, digital biomarkers such as EEG-derived indices, HRV, and NIRS provide continuous real-time physiological monitoring and can integrate with AI-based algorithms for predictive, adaptive anesthesia management. Although no single biomarker meets all criteria for an ideal clinical indicator, combining molecular, genetic, and digital biomarkers represents the most promising pathway toward fully personalized, safe, and outcome-optimized perioperative care.

The coronavirus disease pandemic (2019) has burdened health systems around the world with a large number of severe patients in a short period of time. According to the law of large numbers, a significant number of critically ill COVID-19 patients appear in such conditions which require treatment in the intensive care unit. That percentage of those patients is around 3 - 5% in different countries. It is similar in Serbia; however, every rule has its exceptions. KBC "Dr Dragiša Mišović-Dedinje" in Belgrade has been determined to take care of the most difficult COVID-19 patients since the beginning of the epidemic due to its space, organizational and personnel possibilities. Out of the total number of patients treated in KBC "Dr Dragiša Mišović-Dedinje", about 25% of patients were treated in the intensive care unit for the above mentioned reasons. Guided by valid treatment protocols, Anesthesiology and Intensive Care clinic of the KBC "Dr Dragiša Mišović-Dedinje" has developed its own work protocols for rapid diagnosis, isolation and clinical management of such difficult patients. These protocols are important not only for the treatment of the most severe COVID-19 patients, but also for the best utilization of hospital resources, as well as for the prevention of the spread of the infection to the medical staff. Extensive experience in the treatment of critically ill patients was gained from the entire engagement during the epidemic, experienced doctors, anesthesiologists-intensivists with great knowledge in the field of work in the intensive care unit, but also managers of clinics and institutions, who can share their experience with health care policy makers. It is clear that in the future, the capacities and organization of work in the field of intensive care medicine should be redefined, as well as health workers should be trained to work in the most demanding field of medicine. Expert experience in the form of practical guidelines, derived from over fourteen months of continuous work in the red zone of COVID-19, where they fought for every breath of the patient, in this review are translated into simplified guidelines for orientation of those who find themselves in a similar situation.