University Clinic of Traumatology

Background . Cervical insufficiency, often associated with genital infections, remains one of the leading causes of extremely preterm and early preterm births. Since cervicovaginal infections change the antimicrobial properties of cervical mucus, studies of local immunity can offer new insights into the pathogenesis of this pregnancy complication and help predict preterm birth. Objective . To examine a local immune response in the cervical mucus of pregnant women with cervical insufficiency that leads to preterm birth. Methods . A retrospective cohort study of 106 pregnant women with cervical insufficiency was conducted. These women were diagnosed with cervical insufficiency according to the clinical guidelines (Cervical Insufficiency, 2021). A microscopic and biomolecular analysis of vaginal and cervical material was performed for all patients. Additionally, the following parameters were estimated in the cervical mucus of 58 randomly selected women: total white blood cell count and functional activity and viability of neutrophils, as well as the levels of macrophage inflammatory protein 1β, high-mobility group protein B1, and matrix metalloproteinase-8. A statistical analysis of the results was performed retrospectively, depending on obstetric outcomes: premature and term births. The obtained data were statistically processed using the SPSS software (version 25.0, IBM, USA). Differences in parameter values between the groups were considered statistically significant at p < 0.05. Results . Cervicovaginal infections in women with cervical insufficiency were detected in 84.9% of cases in the preterm birth group and in 57.5% of cases in the term birth group (p = 0.002). In both groups, cervicitis was found to be prevalent. In the immunological study of cervical mucus, the group with cervical insufficiency leading to preterm birth differed most significantly in the number of neutrophil extracellular traps, as well as in the levels of macrophage inflammatory protein 1β and high-mobility group protein B1. Conclusion . Cervicovaginal infections constitute a risk factor for preterm birth. In patients with cervical insufficiency, changes in the local immunity markers of cervical mucus can serve as predictors of preterm birth.

Background/Objectives: Cervical cancer is a prominent source of morbidity and mortality among women, particularly in low- and middle-income nations. Neutrophil Gelatinase-Associated Lipocalin (NGAL), a glycoprotein involved in cancer-related activities, has been proposed as a biomarker; however, its involvement in cervical cancer remains unknown. The study aim is to evaluate the prognostic significance of serum NGAL levels in cervical cancer patients in relation to International Federation of Gynecology and Obstetrics (FIGO) stage, operability, and HPV subtype distribution before and after treatment. Methods: The study involved 130 women, 100 with histologically proven cervical cancer and 30 healthy controls. The serum NGAL levels were determined before and after treatment using an ELISA test. HPV genotyping was carried out using real-time PCR on 21 high- and low-risk subtypes. Results: NGAL levels increased marginally during therapy (from 134 to 144 ng/mL; p = 0.28), but the rise was significant in inoperable patients (p = 0.02) and increased with advanced FIGO stage, although this did not reach statistical significance (p = 0.07). HPV 16 was the most common subtype (26.0%), while women aged 51-60 had the highest overall HPV positive rate (72.7%). There was no significant association between NGAL levels and HPV subtypes (p = 0.17). Conclusion: NGAL does not appear to be an accurate short-term indicator of therapy response. However, increased levels in advanced-stage and inoperable instances indicate prognostic significance. NGAL most likely represents tumor-associated inflammation rather than HPV subtype. These findings support its possible inclusion in future biomarker panels, subject to validation in bigger investigations. Persistent HPV infection in midlife women highlights the significance of ongoing screening.

Involvement of the bone marrow by metastases fromsolid tumors or multiple myeloma (MM) is a critical challenge in oncologic imaging. Lesion detection and staging, as well as accurate assessment of treatment response, disease recurrence, and complications, are key to optimal patient management. This article provides recommendations for performing and interpreting bone marrow MRI in cancer patients. MRI should be the primary imaging modality for patients suspected of having skeletal bone metastases or MM, and should replace radiography, bone scintigraphy, and CT for these indications. Protocols must be tailored to the clinical context and to each specific cancer. Whole-body MRI (WB-MRI) is preferred for a comprehensive assessment, while axial skeleton MRI (AS-MRI) is a fast and reliable alternative for targeted or follow-up evaluations. We recommend standardized protocols that incorporate anatomical sequences (preferably fast spin echo T2 Dixon) and diffusion-weighted imaging (DWI). Quantitative biomarkers, e.g., apparent diffusion coefficient (ADC) and fat fraction (FF), should be implemented to improve diagnostic accuracy and evaluate treatment response. Radiologists must be familiar with the typical patterns of bone marrow replacement by cancer cells, response assessment principles, and common imaging pitfalls. Every medical imaging facility should offer optimal bone marrow MRI and implement these recommendations using available MRI systems and existing disease-oriented guidelines. This ESR Essentials illustrates when, how, and why to perform bone marrow MRI to improve diagnostic precision and oncologic care across a broad range of indications. KEY POINTS: Prefer MRI of the bone marrow over radiographs, bone scintigraphy, or CT for suspected bone metastases of solid cancers and for myeloma staging. Use MRI for diagnosis of bone involvement, disease staging, assessment of lesion response to treatment, detection of recurrence, and assessment of osseous complications. Tailor MRI protocol to cancer type following existing guidelines, targeting either the axial skeleton or the "whole body," and using a panel of sequences with fat-sensitive, fast spin echo T2 Dixon and diffusion-weighted sequences as the fundamental components.

Virgin coconut oil press cake (VCOPC) is a nutrient-rich byproduct of coconut processing, generating millions of tons of waste annually and offering promising potential for sustainable, value-added products and functional ingredients. In this study, we developed a functional ingredient specifically for infant nutrition through a bioprocessing strategy combining enzymatic treatment and lactic acid bacteria (LAB) fermentation. Results showed a 50 % solubilization of VCOPC, a 1000-fold increase in L. paracasei , and the obtainment of a coconut-based functional ingredient (CFI) containing 30 % of proteins both from coconut and by de novo bacteria protein biosynthesis. In vitro digestion results from the infant model in the intestinal phase showed a 67 % degree of hydrolysis, with lysine (51 mg/g) and leucine (78 mg/g) as the most abundant essential amino acids, and arginine (95 mg/g) as the most prevalent non-essential amino acid. Additionally, cysteine, a limiting amino acid in the coconut nutritional profile, was produced through LAB fermentation and liberated during in vitro digestion, reaching a concentration of 7.4 mg/g in the intestinal phase. Colonic batch fermentation of CFI led to the production of acetic, propionic, and butyric acids, with levels exceeding those obtained with Inulin. Overall, the combined bioprocessing strategy of VCOPC produced a functional ingredient suitable for infant nutrition, featuring improved digestibility, a balanced amino acid composition, and promoting gut health. This approach supports the efficient upcycling of a valuable coconut byproduct, enhancing the coconut production chain's value and promoting sustainable food practices. • Bio processing of virgin coconut oil press cake yields infant food ingredient • Digestibility reaches 67 % with a balanced release of essential amino acid • The infant food ingredient promotes gut health and butyric acid production

Background. Vulvovaginal atrophy (VVA) following antitumor treatment is a common and clinically significant complication. At the same time, the immunoinflammatory mechanisms determining the severity and persistence of atrophic changes are yet to be sufficiently studied. The role of extracellular neutrophil traps (NETs) in the pathogenesis of genital tract mucosal damage remains virtually unexplored. Objective: To evaluate blood levels of NET markers – citrullinated histone H3 (CitH3), myeloperoxidase (MPO), cathepsin G (CatG) – in various VVA phenotypes after antitumor therapy and to determine their significance as potential biomarkers of atrophy severity. Material and methods . A cross-sectional comparative study enrolled 215 postmenopausal women divided into five groups as follows: VVA after surgical treatment (n=52), chemoradiotherapy (n=27), antiestrogenic therapy (n=48), VVA without a history of cancer (n=53), and control (n=35). Clinical symptoms, vaginal pH, vaginal health index (VHI), epithelial thickness, and plasma levels of CitH3, MPO, and CatG were evaluated. Statistical analysis was performed using the Mann–Whitney test with Bonferroni correction and calculation of the r effect size. Results . The NETs profile varied depending on the nature of the treatment received. Maximum levels of CitH3 (0,65 [0,50–0,80] ng/ml), MPO (24 [18–30] ng/ml) и CatG (14 [12–16] ng/ml) were found in women after chemoradiotherapy. Antiestrogenic therapy was accompanied by pronounced immunoinflammatory activation of NETs, while surgical menopause and VVA without a history of gynecological cancer were associated with moderate and minimal levels, respectively. Intergroup differences between the oncological groups and the control group were statistically significant (p<0.005) with a large effect size according to the Mann–Whitney criterion (r≥0.50). Conclusion . VVA after antitumor therapy is characterized by various immunoinflammatory phenotypes, which are reflected in specific NET profiles. CitH3, MPO, and CatG can be considered pathogenetically significant markers reflecting the degree of immunoinflammatory changes in VVA, thus representing candidates for further research aimed at patient stratification and the development of personalized therapy.

BackgroundEffective chest drainage is essential in thoracic surgery to prevent postoperative complications such as pneumothorax, subcutaneous emphysema, and retained pleural fluid. Although conventional single-lumen chest tubes have been standard practice, their limitations—particularly in the presence of high air leak or bloody effusions—have prompted investigation into more efficient alternatives such as coaxial drains. This study compares the clinical performance of conventional and coaxial drainage systems following video-assisted thoracoscopic surgery (VATS) lobectomy.MethodsIn a prospective, randomized trial, 300 patients undergoing VATS lobectomy for non-small cell lung cancer were assigned to receive either a 24 F conventional tube (CT) group (n=150) or a 24 F coaxial drain (CD) group (n=150). All drains were connected to a digital suction device. Recorded parameters included air flow, pleural fluid volume, drain occlusion, subcutaneous emphysema, drainage duration, hospital stay, and C-reactive protein (CRP) levels from postoperative day (POD) 1 to 5.ResultsDrainage duration was significantly shorter in the coaxial group (4±2 days) compared with the conventional group (6±3 days, P=0.04). Tube occlusion occurred in 30% of CTs versus 4% of coaxial drains (P=0.02). Subcutaneous emphysema was more frequent in the conventional group (56% vs. 38%, P=0.03). CRP levels were significantly lower in the coaxial group on PODs 3 to 5 (P<0.01). Fluid output thresholds on the operative day (>1,000 mL) and POD 1 (>500 mL) were predictive of prolonged drainage.ConclusionsCoaxial chest drains offer superior performance in cases of significant air leakage, reducing complications and postoperative inflammation. Combined with digital drainage systems, they support faster recovery and better compliance with Enhanced Recovery After Surgery (ERAS) protocols. These findings advocate for broader adoption of coaxial drains in thoracic surgical practice.Trial RegistrationClinical Trial Registry, NCT04778826.

AimsSex differences in ischemic heart disease (IHD) mortality remain underexplored from a population-level case fatality perspective. This study evaluates sex-specific disparities in IHD mortality and risk-attributable causes across 27 European Union (EU) countries using Global Burden of Disease (GBD) 2021 data.Methods and resultsWe calculated age-standardized mortality rates (ASMRs), prevalence rates (ASPRs), and mortality-to-prevalence ratios (MPRs) as a proxy for population-level case fatality. To quantify mortality attributable to specific exposures among individuals with IHD, we derived a case fatality index (CFI) by normalizing risk-attributable ASMRs to ASPRs. Z-scores quantified the magnitude and statistical significance of sex differences in MPRs and CFIs (|Z| ≥ 1.96 = P < 0.05; |Z| ≥ 2.58 = P < 0.01). From 2011 to 2021, IHD ASMRs declined by 24.0% in men and 19.1% in women. In 2011, 12 countries showed significantly higher MPRs in women than men. By 2021, Austria (MPR 6.0% vs. 3.6%), Greece (9.4% vs. 5.3%), and Malta (9.3% vs. 4.2%) remained outliers, with Z-scores >2.58 (P < 0.01). CFIs showed that women in these countries faced 40 to 60% higher mortality burdens from hypertension, hyperglycemia, and poor dietary intake. Low intake of omega-3 fatty acids, fibers, vegetables, and nuts/seeds accounted for the largest dietary disparities.ConclusionDespite declining IHD mortality rates, Austria, Greece, and Malta continue to exhibit significant sex disparities, with women experiencing disproportionately higher case fatality. These disparities are largely driven by modifiable cardiometabolic and dietary risks, underscoring the need for sex-specific, regionally tailored prevention strategies.

Introduction: Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risk later in life. Insulin resistance, common in PCOS, heightens the risk of type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. This study explored whether insulin sensitizers could modify traditional cardiovascular risk factors, through influence on insulin resistance. Objectives: To evaluate the impact of Metformin and Myoinositol therapy on glycemic and lipid profiles in PCOS patients, based on body mass index (BMI). Methods: A prospective, randomized clinical study was conducted at the UC for Endocrinology in Skopje (2022-2023). Women aged 18-40 with PCOS (Rotterdam 2003 criteria) were assigned to either Metformin (1500 mg XR) or Myoinositol (2 g + 200 mg folic acid TID) for 6 months. Parameters monitored included BMI, fasting plasma glucose (FPG), HOMA-IR, total cholesterol, LDL-C, HDL-C, triglycerides, lipid accumulation product (LAP), and TG/HDL ratio. Results: Baseline BMI significantly influenced HDL, triglycerides, TG/HDL, and LAP. Myoinositol significantly improved cholesterol regardless of BMI. Among patients with BMI ≥25 kg/m², Metformin significantly reduced FPG (4.65 ± 0.5 vs 5.01 ± 0.3 mmol/L) and HOMA-IR (2.25 ± 0.6 vs 2.94 ± 1.1 mmol/L). HOMA-IR positively correlated with TG/HDL ratio (R=0.2086, p=0.016). Conclusion: Myoinositol improved cholesterol in PCOS patients regardless of BMI. Metformin significantly affected glycemic control in overweight patients. The TG/HDL ratio may serve as a predictive marker for insulin resistance in PCOS.

Abstract Introduction Avascular necrosis (AVN) is not a direct complication of ankylosing spondylitis (AS) but may arise during its course. There have been reports of avascular necrosis in patients treated with glucocorticoids, especially in the post-covid era where patients were exposed to steroids. We present a case of a patient with a long history of ankylosing spondylitis, and development of femoral head avascular necrosis and humeral head avascular necrosis bilaterally, highlighting the complexity of his treatment. Case description A 49 year old patient with a long history of neck pain with limited movement, hip pain and morning stiffness continually treated with nonsteroidal anti-inflammatory drugs and physical therapy from his general practitioner. Due to worsening of his symptoms, he was presented at our clinic where after detailed analysis (sacroiliitis on x-ray and positive HLA-B27) he was diagnosed with ankylosing spondylitis. Treatment with sulfasalazine was initiated, but due to low efficacy, methotrexate was added. He had previously received several intra-articular glucocorticoid injections in both shoulders, and a total endoprosthesis on his right hip was installed as a result of pre-existing avascular necrosis. It is worth noting the development of his avascular necrosis started post-covid, he also endured a course of more than 4 months of systemic glucocorticoids treatment to ease his ankylosing spondylitis symptoms. The patient had received glucocorticoids of 5 mg prednisolone equivalent daily during that period. During his physical examination he didn’t present with the typical restricted movement one would expect from an axial ankylosing spondylitis, with lateral flexion partially limited. MRI revealed avascular necrosis on the head of the left thigh bone and both humerus heads. Treatment with methotrexate and sulfasalazine are continued but glucocorticoid use is suspended. He is expected to undergo surgery. Management remains complex due to the coexistence of avascular necrosis and persistent disease activity. Biologic treatment was withheld due to the need for orthopaedic surgery and concerns about postoperative infection risk. Discussion Consultations with an orthopaedic surgeon are underway regarding surgical treatment of his multiple avascular necrosis. Regarding our treatment, glucocorticoid use is halted as a potential risk factor for steroid induced avascular necrosis. Treatment with methotrexate may also have to be postponed should surgical intervention take place. To stop the progression of ankylosing spondylitis, treatment with IL-17 inhibitors, TNF-α inhibitors or JAK inhibitor is still an option, with current evidence having not shown worsening of avascular necrosis, but data is limited. Despite treatment, the patient developed four avascular necrosis in a rather short period of time, and his baseline disease has not seen much improvement. Notably, the disease shows an atypical peripheral pattern, with somewhat restricted axial mobility, raising considerations about variant spondylarthritis phenotypes. Key learning points Glucocorticoids remain a foundational treatment, though their risk profile continues to challenge long-term management in the treatment of systemic autoimmune rheumatologic diseases. Vigilance should be maintained in patients with autoimmune diseases where almost all of them at some point are exposed to glucocorticoids, with variable intervals and doses. Given the risk the steroids pose, along with other daily medications and the diseases themselves, such cases pose a great challenge to treat pain and restore active movement. Therefore, steroids should be used in the minimal effective dose and shortest interval possible. Surgery remains the final solution to already established aseptic necrosis, but a challenge remains in the further treatment of this patient. Biologic agents such as TNF-α inhibitors, interleukin 17 inhibitors or Janus kinase inhibitors should be taken into consideration at a much earlier stage than we normally initiate. Biologics used in the treatment of ankylosing spondylitis have shown no evidence of avascular necrosis progression, but data is limited. This patient highlights the need for early consideration of biologic agents and close clinical surveillance for steroid-induced adverse effects.