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J. Krnić, Kristina R. Vidovic, Petra Jerković, B. Benzon

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.

Milena Brkić, Tade Popović, L. Latinović, Aleksandra Marković, Zoran Dakic

The presence of thyroid tissue outside its normal anatomical location, between the second and fifth tracheal rings, is defined as ectopic thyroid tissue. Approximately one to three percent of ectopic thyroid tissue is located in the lateral neck. Most cases are asymptomatic and considered benign.However, lateral neck ectopic thyroid tissue may also represent metastatic disease from an occult primary thyroid carcinoma, making accurate diagnosis challenging. A 36-year-old male presented for microwave ablation of a large right-lobe thyroid nodule after five years of ultrasound surveillance. Progressive growth had been documented, and surgery was recommended, but the patient opted for minimally invasive treatment. Repeated fine-needle aspiration of the right-lobe nodule showed benign cytology, thyroid function tests were normal, and no cervical lymphadenopathy was detected. Clinical examination revealed a palpable right thyroid mass causing compressive symptoms and cosmetic concerns. Ultrasound demonstrated a parenchymatous-colloid nodule measuring 3.1 × 4.1 × 2.5 cm in the right lobe, a 0.2 cm micronodule in the left lobe, and an enlarged left lateral cervical lymph node with microcalcifications, highly suspicious for malignancy. During microwave ablation in November 2024, fine-needle aspiration of the suspicious lymph node suggested papillary carcinoma, possibly arising from ectopic thyroid tissue. In February 2025, right lobectomy with excision of lateral neck tissue and lymph node dissection was performed. Histopathology confirmed a benign right-lobe nodule and papillary carcinoma of conventional and follicular variants originating from ectopic thyroid tissue, with microscopic lymphatic invasion and no vascular invasion.Postoperative evaluation revealed elevated serum thyroglobulin levels of 123.6 ng/mL. Computed tomography identified enlarged lateral cervical lymph nodes. Completion thyroidectomy and removal of metastatic lymph nodes were performed. Histology demonstrated a 0.2 cm papillary microcarcinoma in the left thyroid lobe and metastases in three of eleven lymph nodes, while remaining thyroid tissue showed nodular colloid goiter. Follow-up computed tomography and whole-body scintigraphy were normal. The patient received radioactive iodine therapy I-131 150 mCi. Ectopic thyroid carcinoma of the lateral neck is a rare but clinically important entity. Papillary microcarcinoma, despite its small size, may exhibit aggressive behavior and requires careful evaluation. Thermal ablation enabled early detection, appropriate surgical management, and adjuvant therapy, resulting in a favorable oncological outcome and long-term disease control. This case highlights the importance of multidisciplinary assessment, imaging, and histopathological correlation in complex thyroid disease presentations in clinical practice.

S. Tanasković, A. Milačić, Nikola Ružić, Stefan Graovac, Jovan Petrović, Milovan Bojić, Bojan Božić

Background/Objectives: Peripheral arterial disease (PAD) and diabetes mellitus (DM) may produce different and overlapping plantar thermal patterns. This study descriptively characterized whole-foot temperature-distribution patterns in clinically defined healthy, PAD, DM, and combined PAD_DM cohorts. Methods: This single-center, exploratory, cross-sectional observational study included 73 participants: healthy controls (n = 21), isolated PAD (n = 13), isolated DM (n = 19), and combined PAD_DM (n = 20). Right- and left-foot temperature distributions were processed separately for each participant and interpreted as one paired bilateral thermal footprint using patient-level histograms, representative bilateral kernel density estimation (KDE) profiles, and a cohort-derived deterministic rule-based model. The model was developed from the present cohort and was not evaluated as an independent diagnostic classifier. Results: Among healthy controls, 11 of 21 participants (52.4%) were assigned to healthy and 8 of 21 (38.1%) to borderline healthy categories. In the DM cohort, 7 of 19 participants (36.8%) were assigned to DM, 3 of 19 (15.8%) to borderline healthy/suspected DM or controlled DM, 3 of 19 (15.8%) to DM suspected PAD, and 5 of 19 (26.3%) to PAD_DM. In the combined PAD_DM cohort, 15 of 20 participants (75.0%) were assigned to PAD_DM. The isolated PAD cohort was the most heterogeneous: 6 of 13 participants (46.2%) were assigned to PAD_DM, while none were assigned to the isolated PAD output. Conclusions: This exploratory, cross-sectional study demonstrated that whole-foot plantar temperature distributions can descriptively characterize differences among healthy individuals, patients with isolated DM, and those with combined PAD and DM. While healthy controls generally demonstrated symmetric thermal footprints, the DM cohort frequently exhibited globally elevated and compact temperature-distribution profiles, while mixed asymmetric patterns were common in participants with combined PAD and DM. In contrast, the isolated PAD cohort was characterized by pronounced thermal heterogeneity.

Sibtain Ahmed, Melissa M. Budelier, N. Serdarević, J. Wiencek

The rapid expansion of point of care testing (POCT) has significantly transformed clinical decision-making, particularly in acute care settings. Cardiac biomarkers such as troponins (conventional and high sensitivity) and natriuretic peptides are increasingly being deployed at the bedside to expedite diagnosis and guide timely management [1]. While the clinical advantages of POCT are well recognized, its widespread implementation raises important ethical considerations that remain insufficiently addressed [2]. We aim to project that the rapid expansion of cardiac biomarker POCT has outpaced the development of practical ethical guidance for its implementation. In particular, challenges related to analytical reliability, accountability, quality oversight, equitable access, patient autonomy, and environmental sustainability require a structured ethical framework to support safe and clinically responsible use of POCT in cardiac care. One of the primary ethical concerns relates to the trade-off between speed and analytical accuracy. Although POCT offers faster turnaround times, variability in analytical performance compared to central laboratory assays may compromise diagnostic certainty [3]. This is particularly critical in the context of cardiac biomarkers, where even minor inaccuracies can lead to misclassification of myocardial infarction. In cardiac care, such errors carry particularly significant ethical implications because troponin results may directly influence urgent decisions regarding admission, invasive procedures, discharge, or withholding of treatment. This underscores the necessity of an ethical framework to ensure rapid testing does not compromise diagnostic integrity and patient safety.

S. Jusufović, Enra Desevic, Anisa Sahbaz, I. Širbegović, L. Mlaćo

Hypogonadotropic hypogonadism is a rare but important cause of primary amenorrhea. Kallmann syndrome, characterized by gonadotropin-releasing hormone deficiency and anosmia, may be misdiagnosed when prolonged estrogen deficiency results in non-visualization of reproductive organs. A 26-year-old woman with primary amenorrhea and absent pubertal development had previously been diagnosed with uterine and ovarian agenesis. Hormone replacement therapy had been recommended but not initiated. At presentation, she had poor breast development (Tanner stage II), normal external genitalia, and pubic hair consistent with Tanner stage III/IV. Her history revealed progressive hyposmia evolving into anosmia. Hormonal evaluation confirmed hypogonadotropic hypogonadism, and the karyotype was 46,XX. Initial imaging again failed to visualize the uterus and ovaries, raising suspicion of Müllerian agenesis. Pituitary MRI showed hypoplasia, and bone densitometry revealed osteopenia. Estrogen therapy was initiated. Follow-up ultrasound demonstrated uterine development with appropriate endometrial thickness and visualization of adnexal structures. After five months, transvaginal ultrasound confirmed a normal uterus with a trilaminar endometrium and both ovaries, excluding Mayer-Rokitansky-Küster-Hauser syndrome. MRI of the olfactory region showed hypoplastic olfactory structures, confirming Kallmann syndrome. Progesterone was added, resulting in regular withdrawal bleeding. This case highlights that prolonged estrogen deficiency can lead to misdiagnosis as Müllerian agenesis on imaging. Timely recognition and hormone therapy are essential for accurate diagnosis, restoration of reproductive anatomy, and preservation of bone and reproductive health.

Fahrudin Šabanović, Farisa Babic Sabanovic, E. Bećirović, Amir Bećirović, Dragan Piljic

This retrospective study of 98 patients assessed whether hypertensive heart disease (HHD) is associated with angiographic coronary artery disease (CAD) burden, quantified by the Duke CAD Index, and whether HHD or CAD burden influenced revascularization strategy. HHD was independently associated with higher Duke CAD Index values in linear regression (B = 10.33, p = 0.038) and with greater odds of more severe CAD categories in ordinal regression (OR = 3.19, p = 0.015). However, revascularization choice did not differ by HHD status or CAD severity (p = 0.95). A model incorporating age, sex, diabetes mellitus, and HHD demonstrated moderate discriminative ability for predicting severe CAD (AUC = 0.753). These findings suggest that HHD identifies a high-risk coronary atherosclerotic phenotype, but they are hypothesis-generating and require confirmation in larger prospective studies before clinical application.

E. Bećirović, Minela Bećirović, Amir Bećirović, A. Tursunović, Ajla Bajrić, Amil Softić, Adna Mujkić, Elma Mujaković et al.

Background/Objectives: Early risk stratification remains challenging in patients with non-ST-segment elevation myocardial infarction (NSTEMI). The present study evaluated the prognostic value of 24 h high-sensitivity cardiac troponin I (hs-Troponin I) and assessed whether combining biomarkers and echocardiographic parameters improves short-term risk prediction. Methods: This prospective observational cohort study included 170 consecutive adult patients with confirmed NSTEMI who were admitted to a Medical Intensive Care Unit and prospectively enrolled between February 2022 and January 2023. Clinical, routine biochemical, inflammatory, hematological, lipid, and echocardiographic data were collected during index hospitalization. High-sensitivity cardiac troponin I was measured at admission and again 24 h after hospitalization, with the 24 h value used as the principal marker of myocardial injury in the prediction analyses. The primary endpoint was major adverse cardiovascular events (MACEs), defined as cardiovascular death, recurrent myocardial infarction, ischemic stroke, urgent coronary revascularization, or hospitalization for worsening heart failure, within 3 months. Multivariable logistic regression, Cox regression, sequential prediction modeling, and internal bootstrap validation were performed. Results: MACEs occurred in 88 patients (51.8%). Twenty-four-hour hs-Troponin I, but not admission hs-Troponin I, was independently associated with MACEs (OR 1.57, 95% CI 1.09–2.26; p = 0.015) and a shorter time to the first MACE event (HR 1.38, 95% CI 1.07–1.78; p = 0.012). Lower left ventricular ejection fraction (LVEF) was also independently associated with adverse outcomes. The addition of 24 h hs-Troponin I, LVEF, and C-reactive protein improved discrimination from an AUC of 0.665 to 0.759 (optimism-corrected AUC, 0.717), with corresponding improvements in reclassification. A simplified multimarker score was independently associated with event-free survival (HR 2.36, 95% CI 1.53–3.64; p < 0.001). Conclusions: In patients admitted to a medical intensive care unit with NSTEMI, the integration of 24 h hs-Troponin I, LVEF, and C-reactive protein improved short-term risk prediction beyond that of clinical variables alone. A practical multimarker model based on routinely available parameters identified patients at increased risk of adverse cardiovascular outcomes during early follow-up.

Background In patients with heart failure with preserved ejection fraction (HFpEF), left atrial (LA) strain represents a new indicator of mechanical atrial dysfunction and an important prognostic marker. However, the clinical significance of serial changes in LA strain during patient follow-up is still not sufficiently elucidated. Objectives To evaluate changes between baseline and one-year follow-up in LA strain during one-year follow-up in patients hospitalized with HFpEF and to investigate their association with major adverse cardiovascular events (MACE). Methods This prospective observational cohort study included 123 consecutive patients hospitalized due to acute decompensated HFpEF. Comprehensive echocardiographic evaluation was performed during index hospitalization and after 12 months. LA reservoir strain was assessed as peak atrial longitudinal strain (PALS). The primary endpoint was MACE, defined as rehospitalization due to worsening heart failure and/or cardiovascular death during one-year follow-up. Results Patients who developed MACE had lower baseline LA strain, higher LAVI, higher E/e′, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP), higher right ventricular systolic pressure (RVSP), lower tricuspid annular plane systolic excursion (TAPSE), and more impaired left ventricular global longitudinal strain (LV GLS) compared with patients without MACE. Assessment at two predefined time points showed overall improvement in LA strain during follow-up, but patients with adverse outcomes remained characterized by persistently impaired LA strain and an unfavorable hemodynamic profile. Atrial fibrillation was more frequently observed among patients who developed MACE. Conclusion Persistently impaired or worsening LA strain during one-year follow-up was associated with adverse outcomes in patients hospitalized with HFpEF. Assessment of LA strain at baseline and one-year follow-up may improve longitudinal risk stratification beyond conventional echocardiographic parameters.

Andrej Belančić, M. Skelin, Y. Lam, Almir Fajkić, Bruna Perkov-Stipičin, R. Roncato, I. Krečak, M. Lucijanić

Hematological malignancies remain one of the leading causes of morbidity and mortality despite advances in targeted therapies, immunotherapy, and stem cell transplantation. Emerging evidence indicates that treatment efficacy and toxicity depend not only on the choice of therapy but also on its timing relative to the patient's internal circadian rhythm. The circadian clock orchestrates fundamental processes in hematopoiesis and immunity, such as stem‐cell proliferation, leukocyte trafficking, DNA repair, and drug metabolism, while its disruption promotes malignant transformation, therapeutic resistance, and systemic toxicity. This narrative review synthesizes current understanding of circadian regulation in hematopoietic and immune systems, the mechanistic and preclinical foundations of chronotherapy in blood cancers, and the limited but growing body of clinical evidence linking treatment timing with outcome in leukemia, lymphoma, and transplantation. The review also examines practical challenges, including inter‐individual variability, disease‐induced circadian disruption, and hospital workflow constraints, while highlighting emerging technologies, such as transcriptomic clocks, wearable biosensors, and AI‐driven scheduling algorithms, that are poised to enable personalized, time‐aware therapy. By integrating temporal precision into existing therapeutic frameworks, chronotherapy may represent a promising investigational dimension of precision medicine in hematological oncology. However, its clinical value remains to be defined through prospective studies that incorporate validated circadian biomarkers, predefined timing windows, and clinically meaningful efficacy and toxicity endpoints.

Anela Hadžifejzović Trnka, Nermina Žiga-Smajić, Selma Škrbo

Introduction : Older adults with type 2 diabetes mellitus (T2DM) frequently present with multiple comorbidities and complex therapeutic regimens, increasing the risk of potentially inappropriate medication (PIM) prescribing. This study aimed to assess the prevalence of PIM prescribing in geriatric patients with T2DM using the 2019 American Geriatrics Society Beers Criteria. Materials and methods : This observational, retrospective study included 400 geriatric patients (≥65 years) with T2DM. Data on prescribed medications were collected from medical records. Statistical analysis was performed using SPSS 13.0 and Microsoft Excel 2019 ( α = 0.05). Results : At least one PIM was identified in 60.8% of patients. Frequently prescribed PIMs included proton pump inhibitors (13.5%), diazepam (10.3%), and digoxin (6.5%) among medications to be avoided, and diuretics (59.5%) and acetylsalicylic acid (19.0%) among medications to be used with caution. Conclusion : Systematic application of the Beers Criteria may improve pharmacotherapy safety in this vulnerable population.

N. Radivojević, Tamara Terzić, T. Lazarević-Pašti, I. Pašti, N. Potkonjak, Aleksa Luković, Jasmina Mušović, V. Milanković

Biomass-derived porous carbons are promising sustainable adsorbents for wastewater treatment. However, most reported materials require chemical activation, while the relationships between biomass precursor, pore structure, adsorption mechanism, and regeneration remain insufficiently understood. In this work, non-activated carbon materials were prepared from Juglans regia (JR) and Allium sativum (AS) biomass by pyrolysis at 400 and 900 °C and evaluated for the removal of methylene blue (MB), rhodamine B (RB), crystal violet (CV), and malachite green (MG). Carbonization at 900 °C markedly enhanced porosity, yielding a surface area of 790 m2 g−1 for JR900 and 177 m2 g−1 for AS900, together with predominantly microporous structures and negatively charged surfaces at neutral pH. The pseudo-second-order model best described adsorption kinetics, while intraparticle diffusion analysis indicated a multistep adsorption process. Equilibrium data were well fitted by both Langmuir and Freundlich isotherm models. JR900 exhibited the highest adsorption capacities for MB (321 mg g−1) and RB (304 mg g−1), whereas AS900 showed superior performance toward MG (278 mg g−1). Stable dynamic filtration, efficient regeneration, and nearly complete dye recovery demonstrate the potential of these non-activated biomass-derived carbons for sustainable dye removal and recovery from water.

Adna Borovac, I. Mahmutović-Dizdarević, Ilderina Jusufović, Katarina Hafner-Vuk, Monia Avdić Obučić

This research aimed to examine the chemical composition, as well as the antioxidant, antibacterial, and antibiofilm properties of essential oils (EOs) derived from black pine (Pinus nigra J. F. Arnold) and white pine (Pinus sylvestris L.). The essential oils were extracted using the hydrodistillation method and analyzed using gas chromatography-mass spectrometry (GC-MS). The dominant components identified in the EOs were monoterpenes and sesquiterpenes. The antioxidant capacity was assessed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, which revealed that both EOs exhibited moderate antioxidant activity. The antibacterial activity was evaluated against Staphylococcus aureus ATCC 6538 and Extended-Spectrum Beta-lactamase (ESBL) - producing Escherichia coli ATCC 35218, using the agar diffusion method and the microdilution technique. Antibiofilm activity was assessed using the Tissue Culture Plate (TCP) method. The results of the agar diffusion method suggested that P. sylvestris exhibited stronger antibacterial activity compared to P. nigra. This finding aligns with the results of the broth microdilution method, which showed lower minimum inhibitory concentration (MIC) values for the essential oil of P. sylvestris. Staphylococcus aureus investigated in this study formed a moderately adherent biofilm, while ESBL E. coli was identified as strong biofilm former. Tested EOs performed the capacity to change the biofilm-forming category in a species-specific and concentration-dependent manner, with P. nigra EO showing more pronounced antibiofilm effects

Edin Hodžić, Amila Vinčević Hodžić, Timur Cerić, Z. Zvizdić, Amel Hadžimehmedagić

AIM To assess whether the level of inferior mesenteric artery (IMA) ligation independently affects gastrointestinal-specific quality of life after anterior resection for rectal cancer. METHODS A prospective cohort study including 125 patients with stage II-III mid- or upper- rectal adenocarcinoma who underwent open anterior resection with total mesorectal excision between 2020 and 2025 was conducted. Patients were classified according to the intraoperative level of IMA ligation as having either low ligation with preservation of the left colic artery (n = 75) or high ligation proximal to the origin of the left colic artery (n = 50). Gastrointestinal Quality of Life Index (GIQLI; range 0-144) was assessed 6-8 weeks after protective stoma closure. RESULTS GIQLI scores were significantly higher after low IMA ligation compared with high ligation (127.3 ± 5.7 versus 121.6 ± 5.7; p < 0.001). In univariable analysis, high IMA ligation was associated with lower GIQLI scores (B = -5.733; p < 0.001). In multivariable regression analysis excluding the Low Anterior Resection Syndrome (LARS) score, high IMA ligation remained independently associated with lower GIQLI scores (B = -5.016; p < 0.001). In exploratory receiver operating characteristic (ROC) analysis, IMA ligation alone demonstrated moderate discriminatory ability (AUC = 0.689; 95% CI 0.595-0.783), while addition of IMA ligation to established predictors improved model discrimination (AUC=0.790; 95% CI 0.710-0.871). CONCLUSION Low IMA ligation was associated with better postoperative gastrointestinal quality of life following anterior resection for rectal cancer. When oncologically appropriate, preservation of the left colic artery may optimise patient-reported outcomes.

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