Background: Symptomatic neuroma formation and chronic post-amputation pain remain major barriers to functional recovery following lower limb amputation. Active nerve management strategies, such as the Regenerative Peripheral Nerve Interface (RPNI), have emerged as promising techniques for preventing neuropathic pain by providing a biological target for transected nerves. Methods: A retrospective observational study was conducted including 24 adult patients who underwent transfemoral or transtibial amputation. Twelve patients received prophylactic RPNI at the time of amputation, while 12 underwent standard amputation without active nerve management. Incidence of symptomatic neuroma, Tinel's sign, pain intensity (VAS), pain interference (PROMIS Pain Interference 8a) and prosthetic use were evaluated over a 12-week follow-up period. Results: No cases of symptomatic neuroma were observed in the RPNI group (0%), compared to 66.7% in the control group (p < 0.001). At 12 weeks, mean VAS pain scores were significantly lower in the RPNI group (0.4 ± 0.8) compared to controls (5.8 ± 1.7; p < 0.0001). PROMIS Pain Interference scores at 3 months were markedly improved in the RPNI group (44.0 ± 4.5) versus the control group (66.0 ± 5.8; p < 0.001). A higher proportion of RPNI patients successfully used a prosthesis (66.7% vs. 41.7%), although this difference did not reach statistical significance. Conclusion: Prophylactic RPNI during lower limb amputation effectively prevents symptomatic neuroma formation and significantly reduces post-amputation pain, with favorable functional outcomes. These findings support routine active nerve management as a strategy to optimize rehabilitation and quality of life in amputee patients.

Introduction: Standard dialysate sodium concentration (sDNa) may not adequately reflect individual sodium requirements in each hemodialysis patient, potentially contributing to interdialytic weight gain (IDWG), hypertension and inflammation. The aim of this study was to compare clinical and biochemical outcomes between individualized and standard dialysate sodium prescriptions and to assess factors associated with mortality. Materials and Methods: This was a prospective interventional study conducted in two phases. In the first phase, patients were treated with standard hemodialysis (HD) using a fixed dialysate sodium concentration of 138 mmol/L. In the second phase, dialysate sodium was individualized based on each patient's pre-dialysis serum sodium concentration. Each patient served as their own control. Outcomes included IDWG, blood pressure, thirst score, dialysis adequacy (Kt/V, URR), nutritional markers, C-reactive protein (CRP), electrolytes, and mortality. Results: Individualized dialysate sodium prescription was associated with a significant reduction in IDWG (1.93 ± 0.64 vs 2.17 ± 0.79 kg; p = 0.001) and improved dialysis adequacy (Kt/V: 1.50 ± 0.24 vs 1.36 ± 0.22; p < 0.001). Survivors had higher serum albumin levels and lower CRP values compared to non-survivors. Serum and dialysate sodium concentrations were not independently associated with mortality. In logistic regression analysis, CRP >10 mg/L showed the strongest observed association with mortality (OR 10.278; 95% CI 1.709-61.826; p = 0.011). Conclusion: Individualized dialysate sodium prescription may improve fluid control and dialysis adequacy in selected patients. Inflammation was significantly associated with mortality in this cohort; however, results should be interpreted with caution due to the limited number of events.

Introduction: Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in the head and neck region. The standard therapeutic approach typically includes surgical intervention followed by adjuvant radiotherapy, which, although necessary, may significantly impair salivary gland function and disrupt redox homeostasis in the oral cavity. Aim: The aim of this study was to evaluate the effect of radiotherapy on the quantity and quality of saliva, assessed through salivary biomarkers FRAS, MDA, and SOD, in patients with oral squamous cell carcinoma who had undergone surgical treatment and subsequent head and neck radiotherapy. Materials and Methods: The study included 20 patients of both sexes, aged 41 to 76 years, who were surgically treated and subsequently underwent head and neck radiotherapy. Unstimulated saliva samples were collected at two time points: before and after completion of radiotherapy. Salivary flow rate was measured immediately after collection, and following sample processing, ferric reducing ability of saliva (FRAS), malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) activity were determined spectrophotometrically. Results: The salivary flow rate was significantly reduced after radiotherapy compared to the pre-treatment values. The post-radiotherapy FRAS levels were significantly lower, whereas MDA levels were significantly higher. SOD activity was slightly higher before radiotherapy compared to the post-radiotherapy values. Conclusion: Our findings confirm that radiotherapy is associated with increased oxidative stress and reduced antioxidant capacity in saliva. Although antioxidants may potentially mitigate radiotherapy-induced complications, their clinical application requires caution due to the possibility of protecting the tumor cells, thereby potentially compromising the oncologic treatment outcomes.

Background: Psychological distress in adolescents and young adults is a major public health concern and is increasingly conceptualized as a multidimensional construct involving overlapping somatic and cognitive symptoms. Understanding its latent structure and heterogeneity is essential for improving the assessment and early intervention. Objective: To examine the latent structure, interdimensional relationships, and subgroup variability of psychological distress using an integrated analytical framework. Methods: A cross-sectional study was conducted in 736 participants aged 15-24 years. Psychological distress was assessed using Conn's Psychological Distress Battery. Exploratory factor analysis (principal axis factoring with oblique rotation) was used to identify latent dimensions. Group differences were evaluated using t-tests and ANOVA, while multiple linear regression identified independent predictors. K-means clustering was applied to standardized factor scores to identify distinct distress profiles. Results: Sampling adequacy was excellent (KMO = 0.98), and Bartlett's test of sphericity was significant (χ[2] = 16116.6, df = 435, p < 0.001), confirming the suitability of the data for factor analysis. A two-factor solution explained 53.5% of the total variance, representing somatic and cognitive dimensions of distress that were strongly correlated (r = 0.85, p < 0.001), suggesting a substantial shared underlying distress component. Male gender and university-level education were associated with higher distress levels, with a small-to-moderate gender effect (Cohen's d = 0.42). In multivariable regression analyses, male gender (β = 0.28, p < 0.001) and university education (β = 0.85, p < 0.001) independently predicted higher distress. Cluster analysis identified three distinct profiles corresponding to high, moderate, and low distress levels. Conclusions: Psychological distress in youth is multidimensional and heterogeneous, characterized by interrelated symptom domains and distinct profiles. These findings support multidimensional and person-centered assessment approaches and may inform more targeted early intervention strategies.

Background: Laparoscopic splenectomy has become the preferred approach for most elective splenic indications; however, conversion to open surgery remains a relevant concern, particularly in complex cases. Long-term institutional experiences provide valuable insight into outcomes, learning curves, and evolving indications. Methods: A retrospective observational study was conducted at a tertiary referral center, including all consecutive patients who underwent laparoscopic splenectomy over a 20-year period. Demographic data, surgical indications, conversion to open surgery, and postoperative hospital stay were analyzed using descriptive statistics. Results: A total of 125 patients underwent laparoscopic splenectomy during the study period. Hemato-logic diseases represented the predominant indication, while trauma, malignant conditions, infectious and parasitic diseases, and accessory spleen removal accounted for a smaller proportion of cases. Conversion to open surgery was required in 13 patients (10.4%). A temporal analysis demonstrated a reduction in conversion rates from the first decade to the second decade of the study, reflecting improved outcomes with increasing institutional experience. Postoperative recovery was generally favorable, with a short postoperative length of hospital stay. Conclusion: Laparoscopic splenectomy is a safe and effective procedure for a broad range of splenic pathologies, most commonly hematologic disorders. Over a 20-year experience, acceptable conversion rates and favorable postoperative outcomes were achieved, with evidence of improvement over time. Careful patient selection, standardized surgical technique, and accumulated surgical experience remain key determinants of optimal outcomes.

Background: Aseptic loosening remains a major indication for revision total hip arthroplasty. The relationship between functional impairment and structural disease burden is clinically relevant but not fully quantified. Objective: To evaluate whether Harris Hip Score is associated with Paprosky defect severity, computed tomography based osteolysis volume, anatomical osteolysis distribution, and fixation type in patients revised for aseptic loosening. Methods: Sixty patients revised for aseptic loosening were analyzed, including 30 cemented and 30 cementless implants. Harris Hip Score was evaluated in relation to Paprosky defect type, femoral, acetabular, and total osteolysis volumes, and Gruen and DeLee and Charnley zone involvement. Multivariable linear regression, interaction models, sensitivity analyses, and influence diagnostics were performed. Results: Harris Hip Score was lower in cementless than cemented implants (35.4 ± 11.42 versus 57.95 ± 9.24; p < 0.001). Functional score declined progressively with increasing Paprosky severity. In the primary adjusted model, Paprosky score was independently associated with lower Harris Hip Score (B = -6.18; p < 0.001), while cementless fixation remained independently associated with lower score (B = -17.01; p < 0.001). The model explained 88.0% of Harris Hip Score variation. Adding osteolysis-volume variables minimally improved model performance. Sensitivity analyses confirmed the stability of the main predictors. Conclusions: Functional impairment in aseptic loosening after total hip arthroplasty is most strongly associated with Paprosky defect severity and fixation type. Computed tomography based osteolysis volume and anatomical zone mapping provide complementary structural information for revision planning.

Technological advancement and industrialization have significantly increased human exposure to xenobiotics, a diverse group of foreign chemical substances with potential toxic effects. Xenobiotics include pharmaceuticals, pesticides, personal care products, industrial chemicals, and environmental pollutants. The liver, as the primary organ responsible for biotransformation, plays a central role in the detoxification and activation of these compounds. However, metabolic processes may generate reactive intermediates that contribute to hepatocellular injury. This review provides a comprehensive overview of xenobiotic classification, mechanisms of hepatic biotransformation, and the molecular pathways underlying xenobiotic-induced hepatotoxicity. Special emphasis is placed on oxidative stress, reactive metabolite formation, and immune-mediated mechanisms. Clinical manifestations, diagnostic approaches, and current management strategies are also discussed. Understanding these processes is essential for early detection, prevention, and improved therapeutic outcomes in patients with xenobiotic-induced liver injury..

The kidneys of newborns are morphologically and physiologically different from those of children and adults. Embryonic kidney development begins at the 3rd week after conception and ends at 32-35 weeks prenatally, while in premature infants it continues for some time after birth. Neonatal kidney function is "immature", due to high vascular resistance and low renal blood flow. Therefore, neonatal kidneys are particularly vulnerable to the effects of hypoperfusion. Predisposing factors for the occurrence of acute kidney injury (AKI) in newborns are certain clinical conditions such as prematurity, respiratory distress, sepsis, asphyxia, meconium aspiration, and congenital heart disease. Timely treatment of associated comorbidities reduces the risk of kidney injury in newborns. Diagnosing AKI in newborns is accompanied by certain difficulties due to the lack of blood samples for analysis, especially in premature babies, and variable glomerular filtration due to immaturity of renal function. Early detection of kidney injury provides an opportunity for timely and appropriate treatment, which leads to a better outcome and prognosis of the disease. Renal markers, especially NGAL, enable early diagnosis of AKI even in the first hours of its occurrence, when the disease is not clinically manifested. Due to the possibility of developing chronic kidney disease, monitoring of children at risk is necessary. Extremely premature babies and those with oliguric AKI are susceptible to neurocognitive disorders, anxiety and depression. Therefore, long-term multidisciplinary follow-up of children who manifested acute kidney injury in the neonatal period is warranted.

Introduction: Self-esteem represents a key aspect of the psychological development during adolescence and the emerging adulthood. Existing evidence indicates that the higher self-esteem is associated with the greater wellbeing, emotional stability, and resilience. Despite this, cross-cultural patterns remain insufficiently examined, particularly within the Southeast Europe. The aim of this study was to explore the latent structure of self-esteem and to assess age- and gender-related differences among adolescents and young adults in North Macedonia. Subjects and methods: The study included 510 participants (285 females and 225 males) recruited from high schools and universities in Skopje, North Macedonia. Self-esteem was measured using a culturally adapted version of the Janis-Field Scale. Confirmatory factor analysis (CFA) was applied to evaluate the proposed three-factor model. Internal consistency, regression analyses, and demographic comparisons were conducted using RStudio. Results: The three-factor model showed excellent fit indices (CFI = 0.992; TLI = 0.988; RMSEA = 0.047), supporting the validity of the structure comprising Self-Acceptance, Motivation, and Emotional Peace. Self-Acceptance emerged as the strongest predictor of overall self-esteem (β = 0.68, p < 0.001). A small gender difference was identified, with males reporting slightly higher self-esteem scores; however, the effect size was not substantial. Age-related analyses indicated a modest decline in self-esteem among the older participants, with university students exhibiting greater variability in scores compared to the high school students. Conclusion: The findings support a stable multidimensional structure of self-esteem among adolescents and emerging adults in North Macedonia. The results indicate subtle demographic influences and underscore the importance of culturally validated instruments when assessing psychological constructs. These outcomes may inform future educational and mental health initiatives aimed at strengthening youth well-being in the region.

Background: Severe coronary calcification remains a major challenge in percutaneous coronary intervention (PCI), often complicating lesion preparation and stent expansion. Intravascular lithotripsy (IVL) enables controlled plaque modification through acoustic pressure waves, while drug-coated balloons (DCB) offer antiproliferative therapy without leaving a permanent scaffold. Case summary: We report two cases of severe calcified coronary stenosis treated with calcium modification techniques, intravascular lithotripsy, and drug-coated balloon technology. The first 73-year-old patient presented with a non-ST-elevation myocardial infarction. Coronary angiography identified a heavily calcified mid-LAD lesion. Optical coherence tomography revealed severe concentric calcification with a circumferential arc exceeding 270°, thickness 0.76 mm, length 12 mm, MLA 1.9 mm², prompting the use of intravascular lithotripsy (IVL) for lesion modification. The therapy achieved multiple calcium fractures and optimal luminal gain. As final therapeutic modality, drug-coated balloon angioplasty (DCB) was chosen, after which TIMI 3 flow was maintained with no dissection. In the second case, a 53-year-old male patient presented with cardiogenic shock and multivessel coronary artery disease. After the initial life-saving procedure, a second intervention on a heavily calcified 360° arc on the proximal LAD was performed under guidance with intravascular ultrasound (IVUS) with a cutting balloon and IVL, achieving excellent luminal gain, and DCB was used as a final treatment device. At follow-up, the patients remained asymptomatic, underscoring the safety and efficacy of a stent-less IVL + DCB strategy in complex calcified anatomy. Discussion: IVL's excellent safety profile and uniform circumferential action make it especially suitable for thick, concentric calcification. Likewise, contemporary DCB studies in de novo lesions have shown comparable mid-term results to DES in selected patients, supporting a "leave-nothing-behind" philosophy when optimal lesion preparation and imaging guidance are achieved. Take-home message: In appropriately selected patients, IVL-assisted plaque modification followed by DCB can achieve optimal outcomes while avoiding permanent implants and their late complications.

Antimicrobial resistance represents a paramount challenge to global public health in the 21st century. The multidrug-resistant fungal pathogen Candida auris poses a critical and escalating threat to global public health. Characterized by rapid nosocomial transmission, persistent environmental contamination, and resistance to multiple antifungal classes, C. auris challenges healthcare systems worldwide. Its independent emergence across distinct geographic clades and exponential rise in cases, exacerbated by the COVID-19 pandemic, underscore the urgent need for robust, coordinated response. This review synthesizes the current knowledge on C. auris with a focus on its implications for public health policy, particularly in the European and Balkan healthcare settings, where surveillance gaps and cross-border transmission risks remain pronounced. We analyze the key drivers of spread, including diagnostic misidentification, extensive antifungal resistance, and lapses in infection control, and evaluate the strain on surveillance and hospital preparedness. Effective mitigation is fundamentally dependent on implementing comprehensive, multi-faceted infection prevention and control strategies, guided by antifungal stewardship and rapid diagnostics. We conclude that addressing the C. auris threat requires an urgent, coordinated international and regional response focused on strengthening surveillance networks, standardizing diagnostic and infection prevention and control protocols, and fostering data sharing across borders to contain this resilient pathogen.

Worldwide, new technologies appeared to be inevitable for human being. Man is the creator of all these technologies but the core question is whether these innovations are dangerous and threatening for creativity, especially in arts. Technology significantly influences art creativity by providing new tools and mediums, such as digital painting and virtual reality, which expand the artistic possibilities. It also enhances the accessibility, allowing artists to reach wider audiences and fostering inclusivity within the art community. This relationship between art and technology isn't new, but the digital revolution has accelerated changes at an unprecedented pace, creating exciting new possibilities while challenging the traditional notions of creativity, ownership, and what we even consider "art" in the first place. While AI can enhance efficiency, it lacks the instinct, emotion, and nuance that human-driven storytelling provides. Emerging technologies such as Artificial Intelligence (AI), Virtual Reality (VR), and blockchain are re-shaping the creative industries by enabling new forms of expression, expanding access to global audiences, and redefining how art is produced, distributed, and experienced. However, if an AI creates a piece, should the credit go to the machine, the programmer, or the artist who directed it? There is a completely understandable and reasonable concern that AI-generated art may lead to homogenization, where artworks start to look similar due to reliance on the same algorithms and datasets. While the nature of the creative process is under debate, many believe that creativity relies on real-time combinations of known neural and cognitive processes. Every original work, whether it is a music or a painting, contains within it that invisible sign of inimitableness, which Benjamin called 'the aura'. A convinced suspicion of the original work, whether it be a music, novel or a painting, saves within itself that invisible sign of irreversibility dictated to the aura.

Introduction: Fibrotic interstitial lung diseases and pulmonary sarcoidosis represent diffuse pulmonary disorders with different pathological and radiological patterns. High-resolution computed tomography (HRCT) plays a central role in the evaluation of these conditions, enabling detailed assessment of parenchymal abnormalities and their distribution. Aim: To evaluate the relationship between cough characteristics and HRCT imaging patterns in patients with fibrotic interstitial lung diseases (ILDs) (UIP and NSIP) and pulmonary sarcoidosis. Materials and Methods: This retrospective observational study included 120 patients with diffuse lung diseases diagnosed at the University Clinic for Pulmonology and Allergology in Skopje, including 70 patients with fibrotic interstitial lung diseases (UIP and NSIP) and 50 patients with pulmonary sarcoidosis. Clinical data were collected using a structured questionnaire assessing cough characteristics, dyspnea, smoking status, and the MRC dyspnea scale. HRCT scans were analyzed for the presence of reticular changes, ground-glass opacities, micronodules, consolidations, hypoattenuation, traction bronchiectasis, fibrosis, and honeycombing. Associations between clinical variables and HRCT findings were analyzed using the χ² test and Fisher's exact test. P values between 0.05 and 0.10 were interpreted as indicating a statistical trend. Results: Cough was present in approximately 80% of patients with fibrotic interstitial lung diseases. Productive cough was more common in UIP, whereas dry cough was more frequent in NSIP. In pulmonary sarcoidosis, dry cough predominated in the early stages, while productive or mixed cough was more common in advanced disease. Dyspnea was highly prevalent in fibrotic ILDs and increased with sarcoidosis stage. HRCT patterns characterized by perilymphatic and peribronchovascular micronodules were more frequently observed in patients without cough, whereas fibrotic abnormalities, including traction bronchiectasis and pulmonary fibrosis, were associated with more pronounced respiratory symptoms. Conclusion: Respiratory symptoms in diffuse lung diseases show significant associations with HRCT imaging patterns. Fibrotic interstitial lung diseases are associated with more pronounced cough and dyspnea, whereas pulmonary sarcoidosis demonstrates milder symptoms in the early stages and increasing respiratory impairment in advanced stages.

The glycoengineered humanized monoclonal type II anti-CD20 antibody obinutuzumab is widely used in the treatment of patients with chronic lymphocytic leukemia (CLL), most commonly in combination with other therapeutic agents. The aim of this single-centre retrospective study was to evaluate the treatment patterns and clinical responses in patients with CLL treated with obinutuzumab-based combination regimens at the University Clinic of Hematology, Skopje. We analyzed 90 patients with CLL treated with obinutuzumab-based regimens between 2019 and 2024. Obinutuzumab was administered in combination with chlorambucil (56.6%), fludarabine-cyclophosphamide (26.6%), bendamustine (11.1%), CVP (4.4%), or venetoclax (5.5%). The treatment was given as first-line therapy in 57.7% of patients and in the relapsed/refractory setting in 42.3%. The median age at initiation of obinutuzumab-based therapy was 66.9 years. The overall response rate to obinutuzumab-based treatment was 45.5%. The median follow-up after treatment was 15.6 months. In this real-world single-centre experience, obinutuzumab-based combination regimens showed measurable clinical activity in routine practice across different treatment lines. Longer follow-up and larger patient cohorts are required to better characterize the durability of the responses and outcomes in the specific treatment subgroups.