Vojnosanitetski pregled

Genetic polymorphism and pharmacokinetics/toxicokinetics of carbamazepine: a general review

Aleksandra Kovačević — 2026-03-27

Carbamazepine (CBZ) is a widely used medication in treating epilepsy, bipolar disorder, and neuropathic pain. Its pharmacokinetic profile is highly variable due to slow absorption, extensive metabolism, and auto-induction. Genetic polymorphisms affect transporters and metabolic enzymes, additionally modifying therapeutic response, and lead to nonlinear and unpredictable toxicokinetics in overdose. CBZ is primarily metabolized by cytochrome P450 (CYP) enzymes CYP3A4, CYP3A5, and CYP2C8 to the active metabolite CBZ-10, 11-epoxide (CBZ-E), with subsequent hydrolysis by epoxide hydrolase 1 (EPHX1) and glucuronidation by uridine diphosphate glucuronosyltransferase 2B7 (UGT2B7), with other CYPs additionally contributing to the formation of reactive intermediates and inactive CBZ metabolites. Polymorphisms in genes encoding enzymes (EPHX1, CYP3A4/5, and UGT2B7) and transporters (ABCB1, ABCC2, RALBP1) can affect CBZ and CBZ-E exposure, maintenance dose, and the risk of adverse drug reactions. In overdose cases, CBZ exhibits saturable epoxidation, which leads to the accumulation of the drug and its active metabolite, prolonged elimination, and neurotoxicity, while serum concentrations correlate poorly with clinical findings. Therapeutic monitoring of the drug and its active metabolite in patients’ blood, together with pharmacogenetic testing, could improve both the individualization of therapy and the management of overdose.

A retrospective cohort study of survival in patients with healthcare-associated infection caused by Klebsiella pneumoniae – clinical, phenotypic, and genotypic predictors in a tertiary healthcare institution in Serbia (2022–2023)

Marko Simonović — 2026-03-27

Background/Aim. Klebsiella (K.) pneumoniae is a frequent cause of healthcare-associated infections (HAI), particularly in intensive care units. Carbapenem-resistant strains represent a serious threat due to high mortality and limited therapeutic options. The aim of this study was to identify clinical predictors of 30-day mortality and to determine the presence of carbapenemase genes among K. pneumoniae isolates. Methods. A retrospective cohort study was conducted at the Military Medical Academy in Belgrade, Serbia. It included 121 patients with HAI caused by K. pneumoniae between January 2022 and December 2023. Clinical data were collected through active HAI surveillance. Isolation and antimicrobial susceptibility testing were performed according to standard microbiological procedures, and detection of carbapenemase genes was carried out using multiplex polymerase chain reaction. Survival was analyzed using the Kaplan-Meier method, and predictors of mortality were assessed using Cox regression analysis. Results. Thirty-day mortality was 59.5%. High resistance rates were observed to aminoglycosides (84.3%), fluoroquinolones (94.2%), and carbapenems (95.9%), while 67.8% of isolates were multidrug-resistant. The most common gene was bla_OXA-48-like (45.5% in 2022 and 65.9% in 2023), followed by bla_NDM (22.7% in 2022 and 4.5% in 2023), while bla_KPC was detected only in isolates from 2023 (23.9%). The most frequently detected combination of carbapenemase genes was bla_NDM + bla_OXA-48-like (31.8% in 2022 and 5.7% in 2023). Detected genes had no significant effect on survival. Age ≥ 70 years, bloodstream infection, and intensive care units stay were identified as independent predictors of 30-day mortality. Conclusion. The high mortality among patients with HAI caused by carbapenem-resistant K. pneumoniae strains was primarily associated with patient characteristics and disease severity rather than the presence of specific carbapenemase genes.

Clinical treatment of wounds using nano platelet-rich plasma

Yongjun Xu — 2026-03-27

Background/Aim. Chronic refractory wounds are hard-to-heal lesions that are susceptible to bacterial and other pathogenic infections, leading to additional tissue damage and a significant reduction in patients’ quality of life. The aim of this study was to examine the efficacy of nano platelet-rich plasma (PRP) – nano-PRP compared with conventional PRP in the clinical treatment of wounds. Methods. The study included a total of 96 patients with chronic refractory wounds, including wounds caused by trauma and pressure ulcers, admitted between June 2021 and June 2023. According to the treatment applied, the patients were divided into two groups: the observation group (OG) (n = 47) with nano-PRP treatment and the control group (CG) (n = 49) with conventional PRP treatment. Group differences were analyzed using independent-samples t-tests for continuous variables and Chi-square tests for categorical variables. Results. The overall treatment efficacy in the OG was significantly higher than that in the CG (p < 0.05). After treatment, the visual analog scale score decreased in both groups compared with baseline, with the OG showing significantly lower scores than the CG (p < 0.05). The wound healing rate was also significantly higher in the OG (p < 0.05). Moreover, nano-PRP-treated patients exhibited improved outcomes for scar hyperplasia and a shorter wound healing time relative to the conventional PRP-treated group (p < 0.05). Conclusion. Compared with conventional PRP, nano-PRP demonstrates superior wound healing efficacy in patients with chronic refractory wounds, is associated with greater pain relief, and results in improved aesthetic outcomes. These findings suggest that nano-PRP may represent a more effective therapeutic option than conventional PRP for the clinical management of difficult-to-heal wounds.

Quantitative analysis of capsular microvasculature in relation to the thickness of chronic subdural hematoma

Boban Jelenković — 2026-03-27

Background/Aim. Chronic subdural hematoma (CSDH) is an extra-axial, encapsulated, slow-growing hemorrhagic collection of blood, accompanied by local coagulopathy. This contributes to continuous re-bleeding from the newly formed capsule of hematoma, which leads to slow but progressive enlargement of the hematoma, with the potential to develop into a compressive intracranial lesion. The aim of this study was to investigate the relationship between the proliferation of sinusoid blood vessels and the growth and diameter of the CSDH. Methods. In this study, 33 cases of CSDH treated operatively were analyzed. A biopsy specimen (average size 3 × 3 mm) was obtained from the parietal capsule of the hematoma. The biopsied tissue samples were fixed in aqueous 4% buffered formaldehyde, routinely processed into paraffin-embedded slides, and immunohistochemically stained for the presence of the CD34 antigen. The profiles of microvascular bed blood vessels marked for CD34 were quantified, and the number of capillaries and sinusoids was expressed per one mm². Results. The variables age and number of blood vessels showed a statistically significant association with the increase in hematoma volume (β = 0.422, p = 0.007; β = 0.486, p = 0.022, respectively). Older patients had a higher risk of enlarged hematoma volume, as did patients with a larger number of sinusoidal blood vessels. Conclusion. The number of sinusoids in the parietal capsule of CSDH per surface unit of 1 mm² positively correlates with hematoma thickness, which emphasizes the importance of vascular theory in the development of a hematoma. Although CSDH is one of the most common neurosurgical diseases, its pathogenesis is still not fully understood. Further research in this field is necessary to develop potential new therapeutic options that would provide more comprehensive treatment modalities.

Analysis of the effect of high-frequency electromagnetic radiation on electroencephalography wave frequencies

Boban Biševac — 2026-03-27

Background/Aim. Interest in the effects of electromagnetic fields on the human organism has grown significantly with the advent of digital mobile communication systems, which employ pulsed high-frequency electromagnetic fields. In standby mode, a mobile phone does not emit significant signal power, while during active communication, the intensity of the electromagnetic field may reach values of up to 250 mW. The aim of this study was to examine whether exposure to high-frequency electromagnetic fields affects the frequency of electroencephalography (EEG) waves. Methods. The study included 60 participants (30 males and 30 females). Each participant underwent two consecutive EEG recordings, each lasting approximately 20 min. The first EEG recording was performed at rest, without exposure to an electromagnetic field generator. This was followed by a second EEG recording while using a mobile phone for 10 minutes on one ear, then a break of about 2 minutes was made and the recording was repeated on the opposite ear, also for 10 minutes. A standard mobile phone was used as the source of the high-frequency electromagnetic field. Results. The analysis of EEG wave frequencies revealed no statistically significant differences in either sex before and after mobile phone exposure in the alpha, beta, or delta frequency bands. A change in the theta frequency band in female participants following mobile phone exposure was localized to the right hemisphere. Conclusion. Methodological limitations are the most likely reason for the absence of recorded changes in the majority of participants. The observed effects may be sufficiently subtle or infrequent to evade detection by standard EEG recordings. Therefore, the lack of observed changes cannot be interpreted as evidence that high-frequency electromagnetic fields have no effect on EEG activity.

Trifid and tetrafid renal sinus: A rare anatomical variation present in a pediatric patient

Edis Çolak — 2026-03-27

Introduction. The anatomical variations of the renal sinus appear as hyperechoic areas on ultrasonography, which may be misinterpreted as true hyperechoic masses like renal angiomyolipomas. Case report. A 10-year-old girl was referred to a tertiary children’s hospital due to suspected bilateral renal angiomyolipomas. Upon admission, laboratory test results were within normal reference ranges. Ultrasonographic examination revealed that both kidneys had a normal position and size. On the sagittal ultrasound scan of the right kidney, three columnar masses extending across the sinus were observed, creating the appearance of three hyperechoic zones, indicating a trifid renal sinus. On the sagittal ultrasound scan of the left kidney, multiple columnar masses extending across the sinus were observed, creating the appearance of four hyperechoic zones, identified as a tetrafid renal sinus. The findings were interpreted as a rare benign anatomical variation with no signs of pathology, and additional radiological imaging was not required. Conclusion. Accurate identification of these variations is crucial to prevent patients from undergoing unnecessary biopsies and additional imaging.