Faculty of Medicine

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PREGNANCY IN A PATIENT WITH A CONGENITAL UNICORN UTERUS AND CONIZATION DUE TO CERVICAL CANCER
(University Ss. Cyril and Methodius in Skopje, 2024)
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Bushinoska, Jasna
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Ivanov, Jordancho
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Rare case of super-response to Cardiac Resynchronization Therapy in Macedonian patient with Dilated Left Ventricular Non-Compaction Cardiomyopathy
(Valley International, 2024-02-24)
Shopov, Bozhin
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Zafirovska, Planinka
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Background: Left ventricular non-compaction (LVNC) is rare cardiomyopathy with increased and prominent endomyocardial trabeculations also known as spongy myocardium. It is often found in association with a dilated cardiomyopathy (DCM) and has high incidence of Heart failure (HF). Cardiac resynchronization therapy (CRT) is currently recommended by the available guidelines for selected patients with Heart failure with reduced ejection fraction (HFrEF). Aim: Our case report aims to highlight the therapeutic benefits and superresponse to CRT in a patient with Left ventricular non-compaction cardiomyopathy and HFrEF. Case report: 55-year-old Macedonian male patient with HFrEF, Left bundle branch block (LBBB) remained symptomatic (NYHA III) despite optimal medical treatment (OMT). Echocardiography and CMR findings were in addition to dilated and left ventricular non-compaction cardiomyopathy. Cardiac resynchronization therapy was indicated and 18 months after implantation of CRT-P device we have achieved complete and utter reversibility of systolic myocardial function (EF from 23% to 53%), left ventricular internal diameter was reduced from 90mm to 64mm, left ventricular end systolic volume (LVESV) was reduced from 319ml to 98ml and patient quality of life significantly improved. Conclusion: Cardiac resynchronization therapy is a safe and valuable method of treatment for patients with HFrEF due to dilated left ventricular non-compaction cardiomyopathy.
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Sex differences in transradial access failure in ST segment elevation myocardial infarction
(Wiley, 2024-09-30)
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Jovkovski, Aleksandar
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Taravari, Hajber
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Kitanoski, Darko
Background Transradial access (TRA) is now the default access site for PPCI, but technically is a more challenging approach mostly due to anatomic challenges connected to the RA. Aims To assess the differences according to sex in radial artery (RA) access site characteristics during primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction (STEMI). Material and Methods All 5092 consecutive STEMI patients from our center in the period from March 2011 until December 2017 were examined. The right proximal radial was the “intention‐to‐treat” access in all patients. Preprocedural RA angiography was performed in all patients. Clinical and procedure characteristics, type of radial anatomy variants, need to use another arterial access sites (the primary endpoint for this study), and procedure time were analyzed by sex. Using logistic regression, we selected predictors of radial crossover. Access site bleeding complications and vascular complications were also recorded. Results The STEMI population in this period included 1326 females and 3766 male patients. Females were older (65 ± 11 years) than males (59 ± 11 years, p < 0.0001). Among standard risk factors, hypertension and diabetes mellitus were more common in women and smoking less common. RA anomalies were more frequent in the females (8.8% vs. 6.5%, p < 0.0001), with complex RA loop and tortuous RA twice as frequent in women. Failure of TRA access as the initially chosen site occurred in 4.6% (61) of females versus 2.5% (97) of male STEMI patients (p = 0.0003). The most common subsequent access site was right ulnar access in both groups (57 and 61% respectively). Access site bleeding complications were more common in women 4.4% versus 3.2%, mirrored in hematomas with EASY score III to V. Clinical RA spasm (RAS) was significantly more frequent in females (5.7% vs. 2.2%, p < 0.0001). Multiple regression analysis identified 5 independent predictors for TRA access crossover: previous TRA, anomalous RA, RAS, along with female sex and diabetes. Conclusion Female sex is a significant predictor of more complex TRA in STEMI. Understanding sex differences and predictors for TRA crossover will strengthen the use of different procedural modalities that can help in preserving a successful wrist access in female STEMI patients.
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Diabetic Kidney Disease Position Paper of the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO), Macedonian Society of Cardiology (MSC), and Scientific Association of Endocrinologists and Diabetologists of Macedonia (SAEDM)
(Walter de Gruyter GmbH, 2024-11-01)
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Diabetic kidney disease (DKD) is a significant and growing global health concern, affecting a substantial proportion of individuals with diabetes mellitus. This position paper of Scientific societies of endocrinologists, nephrologists and cardiologists has been consensually brought at a couple of mutual meetings, aiming to synthesize current knowledge on screening, diagnosis and staging of DKD, emphasizing the need for an early detection and intervention in order to prevent progression to end-stage renal disease (ESRD). The role of glycemic control, blood pressure management, lipid management and the use of reno and cardioprotective agents, including angiotensin-converting enzyme inhibitors, sodium-glucose co-transporter 2 inhibitors and non-steroidal mineralocorticisteroid receptor antagonist has been entirely considered. Furthermore, we highlight the importance of a multidisciplinary approach in the care of patients with DKD, integrating lifestyle modifications and patient education into the clinical practice. This paper advocates for the implementation of standardized screening protocols and the development of personalized treatment strategies to optimize patient outcomes. By addressing the complexities of DKD, we aim to provide a comprehensive framework for healthcare professionals to enhance the quality of care for individuals at risk of or living with this condition.
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Oscillation quenching induced by time-varying coupling functions
(AIP Publishing, 2025-12-01)
Stavrov, Dushko
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Koseska, Aneta
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The oscillatory dynamics of natural and man-made systems can be disrupted by their time-varying interactions, leading to oscillation quenching phenomena in which the oscillations are suppressed. We introduce a framework for analyzing, assessing, and controlling oscillation quenching using coupling functions. Specifically, by observing limit-cycle oscillators, we investigate the bifurcations and dynamical transitions induced by time-varying diffusive and periodic coupling functions. We studied the transitions between oscillation quenching states induced by the time-varying form of the coupling function while the coupling strength is kept invariant. The time-varying periodic coupling function allowed us to identify novel, non-trivial inhomogeneous states that have not been reported previously. Furthermore, by using dynamical Bayesian inference, we have also developed a Proportional Integral controller that maintains the oscillations and prevents oscillation quenching from occurring. In addition to the present implementation and its generalizations, the framework carries broader implications for identification and control of oscillation quenching in a wide range of systems subjected to time-varying interactions.
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Physiological Noise in Cardiorespiratory Time-Varying Interactions
(MDPI AG, 2026-01-19)
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Stavrov, Dushko
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The systems in nature are rarely isolated and there are different influences that can perturb their states. Dynamic noise in physiological systems can cause fluctuations and changes on different levels, often leading to qualitative transitions. In this study, we explore how to detect and extract the physiological noise, in terms of dynamic noise, from measurements of biological oscillatory systems. Moreover, because the biological systems can often have deterministic time-varying dynamics, we have considered how to detect the dynamic physiological noise while at the same time following the time-variability of the deterministic part. To achieve this, we use dynamical Bayesian inference for modeling stochastic differential equations that describe the phase dynamics of interacting oscillators. We apply this methodological framework on cardio-respiratory signals in which the breathing of the subjects varies in a predefined manner, including free spontaneous, sine, ramped and aperiodic breathing patterns. The statistical results showed significant difference in the physiological noise for the respiration dynamics in relation to different breathing patterns. The effect from the perturbed breathing was not translated through the interactions on the dynamic noise of the cardiac dynamics. The fruitful cardio-respiratory application demonstrated the potential of the methodological framework for applications to other physiological systems more generally.
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MECONIUM ILEUS AS INITIAL PRESENTATION OF CYSTIC FIBROSIS: A RETROSPECTIVE CASE SERIES FROM A MACEDONIAN PEDIATRIC CYSTIC FIBROSIS CENTER
(University Ss. Cyril and Methodius in Skopje, 2025-12-16)
Krsteska, Elena
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Spirevska, Lidija
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Andreevska Stepanovska, Andrijana
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Jordanova, Olivera
Introduction: Meconium ileus (MI) is often the earliest clinical sign of cystic fibrosis (CF), caused by intestinal obstruction due to thickened meconium from CFTR dysfunction. MI is commonly associated with severe CFTR mutations (classes I-III), which impair chloride and bicarbonate transport. Case report: We report a retrospective case series of six neonates with MI, diagnosed with CF at Pediatric CF Center at University Children’s Clinic, Skopje, over the last eight years. During this period, newborn bloodspot screening (NBS) program for CF was conducted, based on two sequential measurements of immunoreactive trypsinogen (IRT) and IRT-IRT protocol. All infants presented with early intestinal obstruction requiring surgical intervention, including enterotomy and ileostomy. Postoperative care included pancreatic enzyme therapy and nutritional support. CF diagnosis was confirmed via sweat chloride testing and genetic analysis, which showed a predominant presence of the F508del mutation in homozygous or compound heterozygous forms. Despite timely surgical intervention, three infants experienced severe complications and early mortality. It is noteworthy that one of these cases had false-negative NBS result, highlighting limitations of the IRT-IRT protocol in MI cases. The remaining patients showed varied recovery and nutritional outcomes. Conclusions: MI is a known cause of false-negative results in CF NBS, as IRT levels may be low in affected neonates. Therefore, any newborn presenting with MI should be presumed to have CF until proven otherwise. Confirmation requires sweat chloride testing and genetic analysis. These findings support the need for revised CF NBS protocols in all MI cases to ensure timely diagnosis and management.
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Current Status of Newborn Screening in Southeastern and Central Europe
(MDPI AG, 2026-03-02)
Požun, Nika
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Perko, Daša
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Barić, Ivo
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Baša, Mihail
Newborn screening (NBS) is a well-established public health program that enables early detection and treatment of rare disorders in newborns, preventing severe complications or death. Despite its recognized importance, the scope and implementation of NBS programs vary across Southeastern (SE) and Central Europe. This study aimed to evaluate the current status of NBS in 16 countries of SE and Central Europe and assess progress since the previous survey in 2021. A structured questionnaire was distributed to national experts between April and December 2025, collecting data on program organization, coverage, diseases included, laboratory methods, confirmatory testing, consent practices, and future expansion plans. All countries reported universal screening for congenital hypothyroidism, except Kosovo, where a national NBS is in the process of being established. Expanded NBS using tandem mass spectrometry was available in Austria, Bulgaria, Croatia, Cyprus, Greece, Hungary, North Macedonia, Romania, and Slovenia. Spinal muscular atrophy screening became universal in Austria, Croatia, Hungary, Serbia, and Slovenia. Most countries reported plans for further expansion, with congenital adrenal hyperplasia, severe combined immunodeficiency, spinal muscular atrophy, and cystic fibrosis being the most frequently targeted conditions. Although notable infrastructural progress has been achieved, financial constraints, lack of staff, and organizational barriers remain key challenges. The study’s assessment of program effectiveness was further limited by the absence of region-wide systems for capturing end-to-end performance indicators, such as the age of the infant at treatment initiation or missed cases. Regional collaboration and adoption of best practices are therefore vital to ensure equitable access and continuous advancement of NBS programs.
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Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey
(Oxford University Press (OUP), 2025-04-01)
Scheer, Christian S.
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Giamarellos-Bourboulis, Evangelos J.
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Ferrer, Ricard
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Idelevich, Evgeny A.
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Annane, Djillali
Rationale Early detection, standardized therapy, adequate infrastructure, and strategies for quality improvement should constitute essential components of every hospital’s sepsis plan. Objectives To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute-care hospitals. Methods A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals. This included the use of sepsis definitions, the implementation of sepsis guideline recommendations, diagnostic and therapeutic infrastructure, antibiotic stewardship, and quality improvement initiatives (QIIs) in hospitals. Measurements and Main Results A total of 1,023 hospitals in 69 countries were included. Most of them, 835 (81.6%), were in Europe. Sepsis screening was used in 54.2% of emergency departments (EDs), 47.9% of wards, and 61.7% of ICUs. Sepsis management was standardized in 57.3% of EDs, 45.2% of wards, and 70.7% of ICUs. The implementation of comprehensive QIIs was associated with increased screening (EDs, +33.3%; wards, +44.4%; ICUs, +23.8% absolute difference) and increased standardized sepsis management (EDs, +33.6%; wards, +40.0%; ICUs, +17.7% absolute difference) compared with hospitals without QIIs. A total of 9.8% of hospitals had implemented ongoing QIIs, and 4.6% had invested in sepsis programs. Conclusions The findings indicate that there is considerable room for improvement in a large number of mainly European hospitals, particularly with regard to early identification and standardized management of sepsis, the availability of guidelines, diagnostic and therapeutic infrastructure, and the implementation of QIIs. Further efforts are required to implement a more comprehensive and appropriate quality of care.
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Safe pediatric one-lung ventilation in a resource-limited setting: an age- and weight-guided approach
(Springer Science and Business Media LLC, 2025-12-10)
Sulejmani, Haris
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Golubic, Sanja
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Background One-lung ventilation (OLV) in children is technically demanding due to small airway calibers, variable bronchial anatomy, and limited pediatric-specific devices. Challenges are greater in resource-limited settings where double-lumen tubes (DLTs) and fiberoptic bronchoscopes are not consistently available. Methods We retrospectively reviewed five consecutive pediatric patients (ages 4–13 years) who underwent thoracic surgery with OLV between 2022 and 2024. Case summaries highlighted device choice, confirmation method, and perioperative challenges. Variables included demographics, diagnosis, surgical side, isolation technique, OLV duration, ventilatory parameters, arterial blood gases, and defined outcomes (desaturation, hypercarbia, hemodynamic instability, device dislodgement, and postoperative complications). Results Lung isolation was achieved with DLTs in two older patients and bronchial blockers in three younger ones, guided by age and weight. OLV lasted 105–150 min. Two children developed transient desaturation (nadir SpO₂ 75%), one experienced hypercarbia (PaCO₂ >50 mmHg), and two had hemodynamic instability. No tube dislodgement occurred. Median ICU stay was 17 h (IQR 8–19), and hospital stay 21 days (IQR 15–21). All patients were discharged in stable condition. Conclusion An age- and weight-based algorithm bronchial blockers for children < 8 years or < 30 kg, DLTs for older/heavier patients enabled safe OLV and preserved oxygenation, even without routine fiberoptic bronchoscopy. Vigilant ETCO₂ monitoring, careful device fixation, and close intraoperative assessment compensated for equipment limitations. This pragmatic workflow demonstrates feasibility in resource-constrained environments, provides practical guidance for clinicians, and is hypothesis-generating for future multicenter studies.

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