AIM:To compare the prognostic performance of early urinary sodium (UNa) and B-type natriuretic peptide (BNP) for predicting 30-day adverse outcomes in emergency department (ED) patients with acute decompensated heart failure (ADHF). METHODS:This prospective observational study was conducted in the ED of Dokuz Eylül University Hospital, Izmir, between January 2025 and July 2025. The study enrolled adults presenting with dyspnea, diagnosed with ADHF, and treated with intravenous loop diuretics. Baseline and 2-hour spot UNa and serum BNP levels were measured. The primary outcome was a composite of intensive care unit admission at the index visit, ED revisit due to ADHF within 30 days, or 30-day all-cause mortality. Patients were compared according to the presence or absence of the composite outcome. Logistic regression and receiver operating characteristic analyses were performed. RESULTS:A total of 117 patients were enrolled, and the composite outcome occurred in 41 (35.0%). Baseline BNP and UNa levels did not differ significantly between the groups. However, 2-hour UNa was significantly lower in patients with the composite outcome than in patients without it (88.0±29.1 vs 107.3±16.6 mmol/L, P<0.001), whereas 2-hour BNP was comparable between the groups. In multivariable analysis, 2-hour UNa remained independently associated with the composite outcome (adjusted odds ratio 0.963; 95% confidence interval 0.942-0.986; P=0.001), while 2-hour BNP did not. In receiver operating characteristic curve analysis, 2-hour UNa showed significant discriminative ability (area under the curve [AUC] 0.739), whereas 2-hour BNP did not (AUC 0.542). The AUC of 2-hour UNa was significantly greater than that of 2-hour BNP (P=0.003). CONCLUSION:Lower 2-hour UNa was independently associated with 30-day adverse outcomes in ED patients with ADHF and may provide early prognostic information on natriuretic response. These findings require validation in larger multicenter studies.
Osteopetrosis is an uncommon inherited skeletal condition arising from impaired osteoclast activity, with its autosomal recessive forms being linked to mutations in the TNFRSF11A gene. This study reports on a three-year-old Chinese girl presenting with recurrent fractures, short stature, and macrocephaly. Radiological examinations revealed diffusely elevated bone mineral density and constricted medullary spaces. Meanwhile, whole-exome sequencing detected compound heterozygous alterations in the TNFRSF11A gene: c.1567?+?2T>A inherited from the father and c.630C>G from the mother. The child underwent haploidentical hematopoietic stem cell transplantation (HSCT) from the father. Post-transplant follow-up showed improved growth (height/weight), resolved anemia, and alleviated optic foramen stenosis. The patient remained free of hepatosplenomegaly. This case report suggests that HSCT holds therapeutic potential for TNFRSF11A-related osteopetrosis and highlights the clinical value of early genetic diagnosis and timely transplantation for optimizing patient prognosis. Larger studies are required to confirm these findings and further guide the clinical management of similar rare disease cases.
AIM:To examine the relationship between laryngopharyngeal reflux-related signs, symptoms, and self-reported vocal complaints in professional classical singers. METHODS:This cross-sectional study enrolled 111 classically trained singers. Participants completed a questionnaire on vocal habits and complaints, as well as the validated Reflux Symptom Score (RSS). Data were collected at the phoniatrics departments of the University Hospital Center Zagreb and the University Hospital Center Osijek in 2023. LPR signs were assessed using flexible nasopharyngolaryngoscopy and the Reflux Sign Assessment (RSA). Spearman's rank correlation, multivariable regression, and multivariate analysis of variance were used to examine associations according to RSA and RSS cutoff values. RESULTS:A total of 29 (26.13%) participants exceeded the RSA cutoff value. Fifty-seven (51.35%) exceeded the RSS cutoff. RSA and RSS total scores were weakly but significantly positively correlated. The total RSS score emerged as a significant predictor of higher RSA scores, although the explained variance was modest. Compared with singers who did not exceed the RSA or RSS cutoff values, singers exceeding RSA or RSS cutoff values demonstrated a different pattern of vocal complaints, with more frequent throat clearing, hoarseness, and other vocal disturbances, vocal fatigue, and post-performance deterioration of voice quality. CONCLUSION:LPR-related signs and symptoms were common in professional classical singers, with subjective symptom burden exceeding objective laryngoscopic findings. The weak concordance between signs and symptoms highlights the multifactorial nature of voice complaints in this population. These findings support an integrated approach combining reflux-oriented management with targeted voice therapy rather than reliance on isolated laryngoscopic findings.
AIM:To evaluate the appropriateness of antiplatelet use across dementia subtypes in older adults and to identify factors associated with inappropriate antiplatelet use. METHODS:This population-based retrospective study enrolled adults aged ?65 years with dementia evaluated at a tertiary geriatric outpatient clinic at Gulhane Training and Research Hospital between 2016 and 2025. Antiplatelet (aspirin or clopidogrel) use was categorized as appropriate use, underuse, overuse, or appropriate non-use according to the 2021-2024 European Society of Cardiology guidelines. Multivariable logistic regression analyses were performed to identify the factors associated with inappropriate antiplatelet use. RESULTS:Among 683 older adults with dementia, 40.7% received antiplatelet therapy. Antiplatelet underuse and overuse were observed in 16.8% and 16.1% of the participants, respectively. Underuse was most prevalent in vascular dementia (38.9%), whereas overuse was most prevalent in Alzheimer disease (20.2%) and frontotemporal dementia (19.0%). In multivariable analyses, antiplatelet overuse was independently associated with diabetes mellitus (odds ratio [OR] 4.31; 95% confidence interval [CI] 1.66-11.16) and inversely associated with current smoking (OR 0.06; 95% CI 0.06-0.67). Antiplatelet underuse was independently associated with female sex (OR 4.44; 95% CI 1.52-12.92). CONCLUSIONS:Our findings highlight the gaps between guideline recommendations and real-world practice and support the need for individualized dementia-sensitive antiplatelet treatment strategies.
AIM:To evaluate patient complaints submitted to the Split-Dalmatia County Committee for the Protection of Patients' Rights, classify them according to the World Health Organization (WHO) Patient Safety Rights Charter, and evaluate the impact of public awareness interventions on reporting patterns. METHODS:We retrospectively reviewed 36 written patient complaints submitted from 2022 to 2024. Complaints were independently coded by two reviewers according to the ten categories of the WHO Charter. Public interventions to enhance awareness and accessibility of reporting channels included poster campaigns, media coverage, and community discussions in 2023-2024. Statistical analyses assessed temporal trends, distribution of violations, and provider categories associated with reported breaches. RESULTS:From 36 complaints, we identified 60 WHO Charter violations, most frequently concerning the right to timely, effective, and appropriate care (38%), dignity, privacy, and non-discrimination (22%), and access to medical records (12%). Two-thirds of reported incidents involved primary care providers, while one-third involved hospital-based providers. Reporting significantly increased following visibility campaigns: charter violations increased from 11 (2022) to 36 (2024), with monthly reporting rates tripling compared with the baseline (rate ratio 3.3; 95% confidence interval 1.7-6.4; P?=?0.001). The range of reported rights also broadened, encompassing all ten Charter categories by 2024. CONCLUSION:This is the first study in Croatia to evaluate systematically coded, committee-reviewed complaints according to the WHO Patient Safety Rights Charter. Our findings suggest that transparent complaint systems and sustained public education are crucial for empowering patients, strengthening accountability, and enhancing patient safety.
AIM:To determine the characteristics of early emergency department (ED) departures, including patients leaving without being seen and leaving during treatment, in a large tertiary center in Croatia. METHODS:We retrospectively reviewed ED visits at University Hospital Center Split from July 12, 2023, to July 12, 2024. The study enrolled patients who had been triaged but left before physician evaluation or before completing diagnostic workup. Pediatric, gynecologic, psychiatric, and infectious disease ED visits were excluded because these specialties are managed separately. Data on demographics, Australasian Triage Scale category, referral type, specialty routing, seasonal/circadian patterns, and 48-hour return visits were extracted from the hospital information system. RESULTS:Among 110?547 patients visiting the ED, 1420 (1.3%) departed early. Their median age was 40 years (interquartile range 25-59); 55.6% were male. Most were low-acuity patients (category 4: 60%; category 5: 29%). Early departures peaked in August-September and between 2 pm and 10 pm daily (maximum at 7 pm). Self-referred patients accounted for 65% of early departures, and 26% had been routed to orthopedics/trauma specialists. Only 5% left during treatment. Within 48 hours, 20% returned to the ED and 12% required other hospital evaluations. CONCLUSION:Early ED departure rate was low. The patients were mostly young, male, low-acuity, and self-referred with trauma-related conditions, presenting during tourist surges and evening hours. These findings underscore the need for dynamic staffing, enhanced triage communication, targeted patient education, and seasonal preparedness to sustain efficient ED performance.
AIM:To evaluate the effects of MCC950, a selective NLRP3 inflammasome inhibitor, on glycemic control, lipid profiles, and sympathetic dysfunction in a streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) rat model. METHODS:Male Wistar rats were rendered diabetic by intraperitoneal injection of STZ (50 mg/kg). T1DM induction was confirmed by persistent hyperglycemia, reduced serum C-peptide, and pancreatic histopathological changes. Diabetic cardiac autonomic neuropathy was established by elevated serum noradrenaline (NA) before treatment. Diabetic rats subsequently received MCC950, insulin, or normal saline for four weeks. Fasting blood glucose, serum lipid profiles, C-peptide, pancreatic histology, and serum NA were evaluated before and after treatment. RESULTS:MCC950-treated rats showed significantly reduced fasting blood glucose, total cholesterol, triglycerides, and LDL-cholesterol (all P<0.0001) levels compared with untreated diabetic rats, while HDL levels remained unchanged, which suggests an improvement in diabetes-associated dyslipidemia. MCC950 treatment also partially restored C-peptide concentrations, improved pancreatic histology, and reduced serum NA levels. CONCLUSION:These findings suggest that NLRP3 inflammasome inhibition may improve metabolic disturbances associated with experimental T1DM. Further studies incorporating direct functional assessments of cardiac autonomic function are required to determine its role in diabetic cardiac autonomic neuropathy.
AIM:To present a five-criterion calibration framework for evaluating artificial intelligence (AI) tools in pathology centered on preserving "brain capital" - the finite cognitive resources available to clinicians - and stabilizing the "diagnostic apex," the point where histological evidence meets clinical judgment. METHODS:Using cognitive load theory (CLT) and implementation science, we developed the Pathology AI Diagnostic Balance - a conceptual model mapping the physician-specimen interaction within working memory and IT infrastructure constraints - and examined it in the context of peer-reviewed case studies of implemented pathology AI tools. RESULTS:The framework identifies five criteria: Contextual Literacy (integration of clinical history), Responsibility (preservation of signing authority), Evidence Gap Analysis (closure of diagnostic uncertainty), Verification (feasibility of quality control), and Opportunity Cost (return on cognitive investment). Successful tools, such as Ki-67 quantification and breast cancer screening, reduce cognitive burden by automating routine tasks or enabling rapid verification. Conversely, tools requiring an exhaustive re-review or producing opaque recommendations deplete cognitive bandwidth, causing decision fatigue and diagnostic errors. CONCLUSION:Pathologists are positioned to exercise evaluative authority over tools that increase extraneous cognitive load. Clinical expertise represents pathologists' most distinctive contribution to AI development: defining which failure modes matter clinically, what context an AI must integrate, and whether a tool serves patient care. By prioritizing cognitive sustainability over purely technical metrics, the profession can ensure AI functions as a genuine enhancement of diagnostic capability rather than an additional burden on diagnostic workflows.
Aim To compare plasma protein and IgG N-glycosylation levels in pediatric patients undergoing acute appendicitis surgery and in those undergoing minor elective surgery. The secondary aim was to explore whether the plasma N-glycome profile may serve as a biomarker of systemic in-flammatory burden in children. Methods This prospective study enrolled children aged 4-16 years undergoing minor elective surgery (n = 38) or surgery for acute appendicitis (n = 19) at Children's Hospi-tal Zagreb from 2017 to 2021. Blood samples were collect-ed preoperatively and 24 hours postoperatively. IgG and total plasma N-glycans were assessed using high-through-put hydrophilic interaction ultra-high-performance liquid chromatography. Derived glycan traits were compared be-tween the groups and across timepoints. Results Compared with elective surgery controls, chil-dren with acute appendicitis exhibited extensive plasma glycomic remodeling. This was characterized by increased branching, sialylation, and antennary fucosylation, along with reduced abundance of less complex glycans, indicat-ing a systemic inflammatory glycan phenotype. IgG gly-cosylation also differed between the groups but showed fewer and less pronounced changes. Minor elective sur-gery, despite increased C-reactive protein levels, did not significantly alter either plasma or IgG glycomes. Twenty-four hours after surgery, children with appendicitis exhib-ited significant postoperative changes only in the plasma N-glycome, while IgG glycosylation remained stable. Conclusion Plasma N-glycosylation reflects inflammatory burden rather than surgical stress. These findings highlight plasma glycome profiling as a potential systems-level bio-marker for assessing acute inflammation and disease se-verity in pediatric populations.
Chronic systemic inflammation is a key driver of disease progression in rheumatoid arthritis and chronic kidney disease (CKD), particularly in patients undergoing long-term hemodialysis. Persistent elevation of proinflammatory cytokines contributes to pain, anemia, endothelial dysfunction, and increased cardiovascular risk, while therapeutic options are often limited by comorbidities and drug intolerance. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that may offer an alternative strategy for systemic inflammatory control. We report on the case of a 56-year-old woman with juvenile-onset rheumatoid arthritis and dialysis-dependent CKD who received three consecutive systemic administrations of MSCs. Baseline evaluation demonstrated elevated inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α. Following treatment, inflammatory parameters were consistently reduced, which was accompanied by improvement in hemoglobin levels and favorable trends in renal function markers. Additionally, pain assessment scores (Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, Visual Analogue Scale) showed clinically significant improvement. The patient also reported significant subjective pain relief and improved overall well-being. Although limited by its single-case design, this report supports the biological plausibility of systemic MSC therapy as a potential immunomodulatory approach in patients with overlapping autoimmune and uremia-associated chronic inflammation. Further controlled studies are warranted.
Forensic DNA analysis has already influenced criminal justice, and serves as a powerful tool for both conviction and exoneration. Despite its scientific foundations and wide application, DNA evidence is vulnerable to interpretive errors, methodological limitations, and cognitive bias, as demonstrated by numerous wrongful convictions identified through the Innocence Project. Recent artificial intelligence (AI) methods, especially probabilistic genotyping, are used to support the interpretation of complex DNA samples, including mixed, low-template, and degraded profiles. However, the repeated utilization of AI-driven forensic analysis can lead to legal and ethical concerns, including procedural challenges in terms of its usability as direct evidence in the procedure. This article examines the implications of AI-based DNA interpretation for criminal justice, with particular attention to evidentiary reliability, due process, institutional accountability, and emerging policy responses in the US and Europe. It draws on parallels with clinical genomics and documented forensic applications of AI, and argues that AI can enhance forensic accuracy and fairness only if integrated within transparent, validated, and ethically governed frameworks that respect fundamental legal protections.
This case report presents an updated interpretation of genetic and chronological data from human remains discovered in Bezdanjača Cave, a Bronze Age burial site located in the Lika region of Croatia. The cave contains a complex necropolis with at least 57 graves and up to 200 individuals, which indicates its use as a collective burial site during the Middle and Late Bronze Age. Based on ancient DNA analysis, 13 males were identified among 38 analyzed individuals, with the majority belonging to the Y-chromosome haplogroup R1b, commonly associated with Bronze Age populations. However, two individuals were assigned to haplogroup I2a1a (I-Y3120). The I2a lineage has deep roots in Europe, and its presence has been confirmed in prehistoric contexts in Croatia and the region. However, newly obtained radiocarbon dates from occipital bones reveal that at least one of the two I2a1a individuals from Bezdanjača Cave dates to the Early Modern period (1645-1950 calibrated CE), which indicates that the remains were deposited in the cave much later than previously assumed. At the same time, these new data do not contradict the possible presence of the I2a1a lineage in Bronze Age populations in this area, as Bronze Age I2a1a samples have been reported from other archaeological sites in Croatia and the wider region. These findings, presented here for the first time, highlight the risks of assuming chronological homogeneity based solely on archaeological context and demonstrate the necessity of direct radiocarbon dating when integrating archaeological and genetic data. An interdisciplinary approach and careful chronological verification in ancient DNA research are essential to avoid misinterpretations in broader population genetic studies.
Advances in forensic genomics, which include massively parallel sequencing, dense single nucleotide polymorphism testing, and forensic genetic genealogy (FGG), have greatly expanded the range of cases in which DNA evidence can generate investigative leads. As a result, the primary limitations in modern forensic DNA analysis are no longer analytical sensitivity or marker availability, but the ability to reason consistently, transparently, and at scale over increasingly complex genetic, genealogical, and contextual information. Current forensic workflows remain predominantly human-centered, relying on manual reasoning that is difficult to standardize, reproduce, document, or scale across growing case inventories. The potential of artificial intelligence (AI) is described as an enabling layer for forensic identity inference, defined here as computational decision-support systems that structure, prioritize, and document reasoning over genetic associations, genealogical structures, and investigative context during identity hypothesis development. While formal statistical inference quantifies evidentiary weight, identity inference governs how evidence is explored, combined, and acted upon during investigations. AI-assisted systems can augment, but not replace, expert judgment by supporting scalable prioritization, relational reasoning, and systematic documentation of analytical decisions, while reducing bias. Properly designed AI-enabled systems offer a path to sustainably scaling FGG while supporting scientific rigor, accountability, and public trust.
Aim To determine the diagnostic yield of comprehensive genetic testing in patients with neuroimaging findings suggestive of lissencephaly spectrum disorders and to characterize novel pathogenic variants contributing to the genetic architecture of the spectrum. Methods We reviewed clinical and genetic findings of 23 patients with neuroimaging features suspected of the lissencephaly spectrum who underwent genetic testing at the Children's Hospital Zagreb between 2016 and 2025. Clinical data were obtained from medical records and outpatient assessments by clinical geneticists. Genetic testing included chromosomal microarray, clinical exome sequencing, and whole-exome sequencing. Results A molecular diagnosis was established in 15 of 23 patients (65.2%). The pathogenic variants involved genes related to microtubule function (DCX, TUBA1A, TUBB2B, DYNC1H1) and variants in transcriptional and regulatory genes (FOXG1, WDR62). Four novel (likely) pathogenic variants were detected in well-established lissencephaly genes (DCX, TUBA1A, FOXG1, and WDR62). Although most cases involved single-gene variants, three patients had pathogenic copy number variants (1q43q44, 22q11.21, and Xq22.3q23 deletions). Conclusion Exome sequencing when used as a first-line test, complemented by chromosomal microarray, provides a high diagnostic yield in patients with lissencephaly spectrum disorders.This integrated approach facilitates precise diagnosis, informs prognosis, enables targeted follow-up, and supports comprehensive genetic counselling.
