University of Split School of Medicine Repository
Not a member yet
2312 research outputs found
Sort by
Application of a smart drill for more precise assessment of drilling depth and angle in orthopedic surgery
Ciljevi: Cilj ove disertacije je razviti i evaluirati pametni sustav bušenja osmišljen za rješavanje izazova u ortopedskoj kirurgiji vezanih za procjenu kuta i dubine. Trenutne ručne metode, koje se oslanjaju na vizualnu procjenu ili ručne mjerače dubine, često rezultiraju pogreškama. Takve pogrešne procjene mogu dovesti do nestabilnosti implantata, produljenja trajanja zahvata i povećanog rizika izloženosti zračenju, kako za pacijente tako i za kirurge. Predloženi sustav koristi napredne senzore i WIFI tehnologije za real-time povratne informacije kako bi se uklonili nedostaci postojećih metoda. Ova tehnologija ima za cilj povećati preciznost kirurga i smanjiti subjektivne ljudske prosudbe. Time studija nastoji postaviti standard za implementaciju takvih sustava kao osnovnih alata u ortopedskim operacijama, s ciljem poboljšanja ishoda za pacijente, smanjenja troškova operacija i stvaranja sigurnijeg operacijskog okruženja. Metode: Razvojni postupak sustava podijeljen je u nekoliko faza, uključujući inovativni inženjerski dizajn, razvoj softvera i eksperimentalnu validaciju. Početna faza istraživanja uključivala je dizajn i izradu prototipa pametne bušilice, modificirane s električnom bušilicom Trixig kao osnovnom platformom. Uređaj je opremljen mikrokontrolerom ESP32 s mogućnošću bežične komunikacije i ključnim senzorima: IMU-om BNO085 za mjerenje kuta i linearnim potenciometrom SLS 130 za praćenje dubine. Kućišta senzora izrađena su pomoću 3D pisača visoke preciznosti koristeći PETG filament. Druga faza istraživanja usmjerila se na razvoj softvera. Program izrađen u jeziku C++ omogućuje real-time povratne informacije o kutu i dubini bušenja, uz mogućnost pohrane podataka za analizu performansi. Eksperimentalna validacija provedena je u kontroliranim laboratorijskim uvjetima i simulacijama kirurških scenarija na sintetičkim modelima kostiju. Za procjenu performansi sustava korišteni su standardni alati, uključujući Vernier mjerač i 3D tehnologije snimanja poput kompjuterizirane tomografije (CT) i strukturiranog svjetlosnog 3D skeniranja. Završna faza bila je usporedna analiza performansi. Sustav je testiran naspram tradicionalnih metoda vizualne procjene kuta i uspoređen s objektivnim mjerenjem duljine kanala kako bi se kvantificirale prednosti sustava kroz statističke metode poput t-testa i analize srednje apsolutne pogreške. Rezultati: Rezultati pokazuju značajno povećanje preciznosti i točnosti pametnog sustava u usporedbi s tradicionalnim metodama. Srednja apsolutna pogreška za kutove inklinacije od 30°, 45° i 60° iznosila je između 0.6° i 1.3°, dok su ručne metode imale pogreške od 1.9° do 4.5°. Preciznost mjerenja dubine pokazala je srednju apsolutnu pogrešku od 0.33 mm ± 0.41 mm, što je usporedivo s vrijednostima dobivenim pomoću Vernier mjerača, što dokazuje da ovaj automatizirani uređaj daje značajno bolju preciznost mjerenja uz kraći postupak nego tradicionalne metode. Sustav je također uspješno monitorirao prekomjerno prodiranje bušilice, čime je povećana usredotočenost kirurga na mogućnost oštećenja mekih tkiva. Zaključak: Pametni sustav bušenja predstavlja značajan napredak u ortopedskoj kirurgiji, omogućavajući modularnost dizajna, bežično upravljanje i real-time povratne informacije, što povećava preciznost i smanjuje troškove u usporedbi sa skupim robotskim sustavima. Sustav je kompatibilan s postojećim kirurškim alatima, smanjujući prepreke za implementaciju. Ograničenja istraživanja uključuju testiranje na sintetičkim modelima i rad samo jednog kirurga, što sugerira potrebu za daljnjim istraživanjima na kadaveričnim modelima i većem broju korisnika. Buduće studije trebale bi također ispitati mogućnost primjene sustava u minimalno invazivnim ili zahvatima vezanim za specifičnu patologiju.Aims: The goal of this dissertation is to develop and evaluate a smart drilling system designed to address ongoing challenges in orthopedic surgery related to angle and depth calculations. Current manual methods, which rely on visual estimation or depth calculations, frequently lead to errors. Such faulty estimations may then further lead to implant wastage, increased procedural time, and risks such as accidental radiation exposure both to the patients and surgeons. The proposed smart system is delivered using advanced sensors and WIFI enabled real-time feedback to overcome the shortcomings of such systems. This technology aims to enhance the precision of the surgeon and reduce subjective human judgments. In doing so, this study attempts to set a benchmark for the adoption of such technologies as standard tools in orthopedic surgery, aimed at improving patient outcomes while lowering operation costs and making the operating environment safer. Methods: Different stages of techniques in the research are applied, from innovative engineering design through software development to rigorous experimental validation. The initial phase was employed in designing and prototyping the smart drilling system. An already commercially available electric drill, Trixig, was modified for use as a platform for integrating advanced technological components. The principle of hardware design was based on the installation of an ESP32 microcontroller that supports wireless communication, and two critical sensors: a BNO085 IMU for angle measurement and an SLS130 linear potentiometer for tracking depth. Custom 3D-printed housings were manufactured from PETG filament using a high-precision 3D printer to house these parts properly, protect them, and make them compatible in a surgical environment. The study's second phase focused on software development. A bespoke application was programmed in C++ to process and display real-time feedback on angle alignment and drilling depth, offering visual aids to guide the surgeon during simulated procedures. This also includes an application for storing measurement data, which was used for further analysis and evaluation of the performance of the systems. Experimental validation was conducted in two stages: preliminary testing in a fully controlled laboratory condition and simulating surgical conditions with synthetic bone models to perform a test in a systematic way without the variability usually introduced with organic tissue. A series of experiments were designed to evaluate the system's performance in both angle and depth measurement. Measurements obtained using the smart drilling system were cross-validated using established methods, including a Vernier gauge for depth tracking and 3D imaging technologies—such as computed tomography (CT) and structured-light 3D scanning—to verify angular accuracy. The experimentation's last stage was devoted to comparative performance analysis. The smart system was, therefore, tested against conventional methods in estimating angles by the visual method and using manual depth gauges to assess improvement in precision and consistency. The advantage quantification of the system over conventional techniques was done with a view of paired t-tests, Shapiro-Wilk testing, and evaluation of mean absolute errors. The proposed paper has adopted a structured approach to present reproducibility and robustness that is necessary for the results. Results: When compared to traditional manual methods, the results demonstrated a significant improvement in accuracy and precision with the smart drilling system. The mean absolute errors for inclination angles of 30°, 45°, and 60° ranged between 0.6° and 1.3°. Compared to manual methods, this is a significant improvement as the errors recorded ranged from 1.9° to 4.5°. The system displayed mean errors of 0.35° ± 0.25° for inclination and 2° ± 1.33° for anteversion using reference angles of 45° for inclination and 20° for anteversion for combined measurements. The system's mean absolute error of 0.33 mm and standard deviation of 0.41 mm, which closely matched values acquired with a Vernier gauge, further demonstrated the extreme precision of the depth measurements. Apart from that, over-penetration was excellently monitored by the system, which is vital in preventing any soft tissue damage. The value of over-penetration, which was on average 5.5 mm ± 1.1 mm, matched the commonly achieved result by expert surgeons. From these results, the smart drilling system is able to reduce variability and increase orthopedic consistency during any surgical procedures. It is also reliable and effective. Conclusion: The conclusion of this dissertation emphasizes that the smart drilling system has the potential to alter orthopedic surgical practices by allowing modularity in design, capability for wireless operation, and real-time feedback, therefore increasing the accuracy and ease of use at low cost compared to expensive robotic systems. Thus, this minimizes implant waste, surgical time, and radiation exposure and thus provides considerable economic and patient care benefits to healthcare institutions. The system is designed to be compatible with the use of existing surgical tools; therefore, it flexibly extends current practices, which again reduces barriers to its adoption. Limitations of the study are stated accordingly. The experiments were conducted on synthetic bone models and the tests were performed by only one experienced surgeon. Consequently, future studies should be performed in cadaveric models, and a larger group of surgeons at various levels of experience should be used in order to further assess the generalizability and strength of this system. Further testing can also be done to see the capacity for the system's use in broadened surgical applications, such as minimally invasive techniques or specific orthopedic pathologies
Development of potential inhibitors of the E6 protein of human papilloma virus
Cilj istraživanja: Identifikacija novih potencijalnih inhibitora E6 proteina humanog papiloma virusa (HPV) za terapijsku primjenu u liječenju bolesti uzrokovanih ovim virusom. Metode: Kristalografska struktura receptora preuzeta je iz Protein Data Bank baze, dok su za identifikaciju farmakofora i probir liganada korišteni softver Discovery Studio 2024 i servis ZINCPharmer. Obrada receptora i liganada provedena je alatima Chimera, Open Babel i Meeko, a molekularno sidrenje na superračunalu pomoću programa AutoDockVina. Rezultati sidrenja potvrđeni su usporedbom RMSD vrijednosti iz AutoDock Vina i AutoDock4. Vizualizacija kompleksa receptor-ligand obavljena je u ChimeraX, dok je analiza vezanja rađena u Discovery Studio 2024. Alat PRED-hERG korišten je za predviđanje kardiotoksičnosti, a fizikalno-kemijska svojstva liganada analizirana su u programu RDKit. Ligandi su rangirani prema rezultatima sidrenja, svojstvima i predviđenoj kardiotoksičnosti. Rezultati: Na temelju farmakoforske mape LxxLL motiva E6AP proteina identificirano je 386 potencijalnih inhibitora. Analizom su procijenjeni afiniteti vezanja, fizikalno-kemijska svojstva i kardiotoksičnost liganada. Za daljnje analize odabrano je 5 molekula s najpovoljnijim karakteristikama i bez kardiotoksičnih učinaka. Zaključak: Identificirane su molekule potencijalni inhibitori E6 proteina HPV-a. Daljnji koraci uključuju njihovu optimizaciju, sintezu i eksperimentalnu potvrdu kako bi se omogućio nastavak razvoja ovih lijekova.Objectives: To identify novel potential inhibitors of the E6 protein of human papillomavirus (HPV) for therapeutic use in treating diseases caused by this virus. Methods: The crystallographic structure of the receptor was retrieved from the Protein Data Bank. Pharmacophore identification was conducted using Discovery Studio 2024, while ligand screening was performed with the ZINCPharmer online service. The receptor was prepared in Chimera, and the ligands were processed using Open Babel and Meeko. Molecular docking was executed on a supercomputer using the AutoDock Vina program, with results validated by comparing RMSD values from AutoDock Vina and AutoDock4. Ligand-receptor complexes were visualized in ChimeraX, and binding analysis was carried out in Discovery Studio 2024. The PRED-hERG tool was employed to predict ligand cardiotoxicity, while physicochemical properties were evaluated with the RDKit program. Finally, ligands were ranked based on docking results, physicochemical properties, and predicted cardiotoxicity. Results: Based on the pharmacophore map derived from the LxxLL motif of the E6AP protein, 386 potential inhibitor molecules were identified. Binding affinities, physicochemical properties, and cardiotoxicity were analyzed. Five ligands with the most favorable binding affinities and no cardiotoxic effects were selected for further analysis. Conclusion: Molecules identified as potential inhibitors ofthe HPV E6 protein require further optimization, synthesis and experimental validation to advance the development of these therapeutic agents
Hormonal analysis in patients with post-traumatic stress disorder
Ciljevi: Cilj ovog istraživanja bio je odrediti serumske vrijednosti hormona u oboljelih od PTSP-a. Dodatni cilj istraživanja bio je ispitati povezanost antropometrijskih obilježja i navika sa serumskim vrijednostima testosterona, TSH-a, kortizola i estradiola. Ispitanici i postupci: U ovo presječno istraživanje uključeno je 45 muških veterana Domovinskog rata koji boluju od PTSP-a i liječe se prema Programu oporavka od traume. Istraživanje je provedeno za vrijeme redovnih pregleda u Centru za psihotraumu. Nakon što su ispitanici potpisali informirani pristanak za uključivanje u istraživanje, od ispitanika su prikupljeni anamnestički podaci, napravljena su antropometrijska mjerenja te uzorkovanje krvi za laboratorijsku analizu. Laboratorijski su određivane vrijednosti ukupnog i slobodnog testosterona, TSH, kortizola i estradiola. Rezultati: Najveći udio ispitanika je imao normalne vrijednosti ukupnog testosterona (76 %), slobodnog testosterona (64%), kortizola (87%), TSH (96%) i snižene vrijednosti estradiola (62%). Skupina ispitanika koji su prema ITM pretili imali su statistički značajno manje vrijednosti ukupnog (10,95 vs. 14,8 vs. 18,5, P=0,008) i slobodnog testosterona (0,21 vs. 0,25 vs. 0,3, P=0,029) u odnosu na skupinu ispitanika s prekomjernom i normalnom tjelesnom masom. Tjelesna masa je statistčki negativno korelirala s vrijednostima ukupnog testosterona (ρ=-0,504, P<0,001), ali nije značajno korelirala s vrijednostima serumskog kortizola (P=0,282), TSH (P=0,147) i estradiola (P=0,239). Skupine ispitanika prema ITM-u nisu imali statistički značajne razlike u prosječnoj vrijednosti kortizola, TSH i estradiola (P=0,297). Ispitanici s PTSP-om koji u prosjeku dnevno konzumiraju manje od 1 IJ alkohola pokazali su statistički značajno niže vrijednosti estradiola u odnosu na ispitanike koji dnevno konzumiraju više od 1 IJ alkohola (74,5 pmol/L vs. 111 pmol/L, P=0,013). Nije bilo značajne razlike među skupinama s obzirom na konzumaciju alkohola u razini ukupnog testosterona (P=0,356), slobodnog testosterona (P=0,649), TSH (P=0,576) i kortizola (P=0,149). Zaključci: Najveći udio pacijenata oboljelih od PTSP-a ima normalne serumske vrijednosti testosterona, kortizola, TSH i estradiola. Tjelesna masa ispitanika značajno negativno korelira s vrijednostima ukupnog testosterona, ali nema značajne korelacije s vrijednostima serumskog kortizola, TSH i estradiola. Ispitanici koji u prosjeku dnevno konzumiraju manje od 1 IJ alkohola imaju značajno niže vrijednosti estradiola u odnosu na ispitanike koji dnevno konzumiraju više od 1 IJ alkohola, ali nema značajne razlika među skupinama s obzirom na konzumaciju alkohola u razini testosterona, TSH i kortizola.Objectives: The primary aim of this study was to determine serum hormone levels in individuals diagnosed with post-traumatic stress disorder (PTSD). An additional objective was to examine the association between anthropometric characteristics and lifestyle habits with serum levels of testosterone, TSH, cortisol, and estradiol. Subjects and Methods: This cross-sectional study included 45 male veterans of the Croatian War of Independence diagnosed with PTSD and undergoing treatment within the Trauma Recovery Program. The research was conducted during routine clinical assessments at the Center for Psychotrauma. Upon providing written informed consent, participants underwent a clinical interview, anthropometric measurements, and blood sampling for laboratory analysis. Laboratory assessments included total and free testosterone, TSH, cortisol, and estradiol levels Results: The majority of participants exhibited serum levels within normal reference ranges for total testosterone (76%), free testosterone (64%), cortisol (87%), and TSH (96%), while 62% had reduced estradiol levels. Participants classified as obese based on BMI had significantly lower levels of total (10.95 vs. 14.8 vs. 18.5, P=0.008) and free testosterone (0.21 vs. 0.25 vs. 0.3, P=0.029) compared to those with overweight and normal body weight. Body weight was significantly negatively correlated with total testosterone levels (ρ=–0.504, P<0.001), but showed no significant correlation with serum levels of cortisol (P=0.282), TSH (P=0.147), or estradiol (P=0.239). There were no statistically significant differences in the mean levels of cortisol, TSH, and estradiol among BMI-based groups (P=0.297). Participants with PTSD who consumed less than one standard unit of alcohol per day had significantly lower estradiol levels compared to those who consumed more than one unit daily (74.5 pmol/L vs. 111 pmol/L, P=0.013). No significant differences were observed between these groups in terms of total testosterone (P=0.356), free testosterone (P=0.649), TSH (P=0.576), or cortisol (P=0.149). Conclusions: The majority of patients with PTSD have serum levels of testosterone, cortisol, TSH, and estradiol within normal ranges. Body weight is significantly negatively correlated with total testosterone levels, while no significant correlations were found with serum levels of cortisol, TSH, or estradiol. Participants who consume less than one standard unit of alcohol per day have significantly lower estradiol levels compared to those with higher alcohol consumption, though no significant differences were found between these groups in serum testosterone, TSH, or cortisol levels
Prevalencija pacijenata liječenih od Gravesove bolesti na području koje pokriva bolnica Sana u Coburgu (Njemačka)
Objectives: The aim of this study is to examine whether there is a higher prevalence of Graves' disease among patients in the catchment area of Sana Hospital in Coburg compared to the average international, particularly European, prevalence rates. The underlying hypothesis assumes that the region served by the hospital exhibits a notably increased occurrence of Graves' disease relative to other European countries. Materials and methods: This retrospective study analyzed anonymized data from 508 patients treated for Graves' disease (ICD-10: E05.0) at the Department of Endocrinology, Sana Hospital Coburg, between January 1, 2018, and January 1, 2023. Patients included had a confirmed primary diagnosis of Graves' disease and received treatment within the specified timeframe. Data were extracted from the Orbis hospital information system, focusing on patient demographics (residence, age, gender) and compared with international prevalence data to assess regional differences. Results: A total of 508 patients were diagnosed with Graves’ disease between 2018 and 2022. The majority were female (68.3%), and the average age was 70.9 years, with the highest proportion in the 81+ age group. Regional analysis revealed the highest annual prevalence in Lauscha, followed by Coburg and Neuhaus am Rennweg. Although some areas showed elevated local prevalence, statistical comparison with international data revealed no significant differences—except for Neustadt bei Coburg, where the prevalence was significantly lower. Conclusion: The findings of this study indicate that the overall prevalence of Graves’ disease in the Coburg region is largely consistent with international trends, particularly those observed across Europe. While certain municipalities, such as Lauscha and Neuhaus am Rennweg, showed elevated prevalence rates, these differences were not statistically significant when compared to international reference values. An exception was Neustadt bei Coburg, where the prevalence was significantly lower. However, this unexpectedly low rate may be influenced by underreporting, data limitations, or regional referral patterns and should therefore be interpreted with caution. The study also confirmed the typical demographic patterns of Graves’ disease, including a higher prevalence in older individuals and a marked predominance among female patients.Ciljevi: Cilj ovog istraživanja je ispitati postoji li viša prevalencija Gravesove bolesti među pacijentima u području koje pokriva bolnica Sana u Coburgu u usporedbi s prosječnim međunarodnim, posebno europskim, stopama prevalencije. Temeljna hipoteza pretpostavlja da regija koju bolnica opslužuje pokazuje značajno povećanu učestalost Gravesove bolesti u odnosu na druge europske zemlje. Materijali i metode: Ovo retrospektivno istraživanje analiziralo je anonimizirane podatke 508 pacijenata liječenih zbog Gravesove bolesti (ICD-10: E05.0) na Odjelu za endokrinologiju bolnice Sana u Coburgu, u razdoblju od 1. siječnja 2018. do 1. siječnja 2023. U istraživanje su uključeni pacijenti s potvrđenom primarnom dijagnozom Gravesove bolesti koji su primili liječenje unutar navedenog vremenskog okvira. Podaci su preuzeti iz bolničkog informacijskog sustava Orbis, s fokusom na demografske podatke pacijenata (mjesto stanovanja, dob, spol) i uspoređeni s međunarodnim podacima o prevalenciji kako bi se procijenile regionalne razlike. Rezultati: Ukupno je 508 pacijenata dijagnosticirano s Gravesovom bolešću u razdoblju između 2018. i 2022. godine. Većina pacijenata bile su žene (68,3 %), a prosječna dob iznosila je 70,9 godina, pri čemu je najveći udio zabilježen u dobnoj skupini iznad 81 godine. Regionalna analiza pokazala je najvišu godišnju prevalenciju u Lauschi, zatim u Coburgu i Neuhausu am Rennweg. Iako su neka područja pokazivala povišenu lokalnu prevalenciju, statistička usporedba s međunarodnim podacima nije otkrila značajne razlike — osim za Neustadt bei Coburg, gdje je prevalencija bila značajno niža. Zaključci: Rezultati ovog istraživanja pokazuju da je ukupna prevalencija Gravesove bolesti u regiji Coburg uglavnom u skladu s međunarodnim trendovima, osobito onima zabilježenima u Europi. Iako su neke općine, poput Lausche i Neuhaus am Rennweg, pokazale povišene stope prevalencije, te razlike nisu bile statistički značajne u usporedbi s međunarodnim referentnim vrijednostima. Iznimka je bio Neustadt bei Coburg, gdje je prevalencija bila značajno niža. Međutim, ova neočekivano niska stopa može biti posljedica nedovoljnog prijavljivanja, ograničenja u podacima ili specifičnih regionalnih upućivanja te je stoga treba tumačiti s oprezom. Istraživanje je također potvrdilo tipične demografske obrasce Gravesove bolesti, uključujući veću prevalenciju kod starijih osoba i izraženu dominaciju među ženskim pacijentima
Management of mineral and bone disorders in patients undergoing chronic hemodialysis
Cilj istraživanja: Svrha ovog istraživanje bila je ispitati regulaciju mineralno-koštanog metabolizma u bolesnika na dijaliznom nadomjesnom liječenju. Ispitanici i postupci: U ovo retrospektivno presječno istraživanje uključeno je 89 bolesnika/ispitanika s terminalnim stadijem kronične bubrežne bolesti koji su na dijaliznom nadomjesnom liječenju na Zavodu za nefrologiju Kliničkog bolničkog centra u Splitu. Bolesnici su podijeljeni u dvije skupine: jedna skupina liječena hemodijalizom (HD), a druga hemodijafiltracijom (HDF). Svi parametri od interesa za svakog bolesnika dobiveni su iz medicinske dokumentacije. Rezultati: Životna dob bolesnika, duljina trajanja kronične bubrežne bolesti i nadomještanja bubrežne funkcije dijalizom nisu korelirale s parametrima mineralno-koštanog metabolizma (svi P > 0,05). Vrijednosti serumskih fosfata iznad gornje granice normale zabilježene su kod čak 61 % HDF bolesnika, ali i kod 42,85 % HD bolesnika. Uzimajući u obzir 9-struki porast PTH kao gornju granicu prihvatljivog raspona, vrijednosti iznad zabilježene su kod 14,28 % HD bolesnika i 29,62 % HDF bolesnika. Najčešće primjenjivani vezač fosfata u obje ispitivane skupine bio je sevelamer, korišten u 71,42 % HD bolesnika i 90,74 % HDF bolesnika. Zaključak: Vrijednosti fosfata i paratireoidnog hormona u bolesnika s terminalnim stadijem kronične bubrežne bolesti bile su lošije regulirane metodom hemodijafiltracije u odnosu na hemodijalizu.Objectives: The purpose of this study was to examine the regulation of mineral and bone metabolism in patients undergoing dialysis as renal replacement therapy. Subjects and methods: This retrospective cross-sectional study included 89 patients with end-stage chronic kidney disease undergoing dialysis as renal replacement therapy at the Department of Nephrology, University Hospital Centre Split. The patients were divided into two groups: one group receiving hemodialysis and the other hemodiafiltration. All relevant parameters for each patient were obtained from medical records. Results: Patient age, duration of chronic kidney disease, and duration of renal replacement therapy with dialysis did not correlate with parameters of mineral and bone metabolism (all P > 0.05). Serum phosphate levels above the upper normal limit were recorded in as many as 61 % of HDF patients and in 42.85 % of HD patients. Taking a ninefold increase in PTH as the upper limit of the acceptable range, elevated values were observed in 14.28 % of HD patients and 29.62 % of HDF patients. The most commonly used phosphate binder in both groups was sevelamer, used by 71.42 % of HD patients and 90.74 % of HDF patients. Conclusion: Regulation of phosphate and parathyroid hormone levels was less effective with hemodiafiltration than with hemodialysis in patients with end-stage chronic kidney disease
Thyroid hormonal status in patients subjected to diagnostic kidney biopsy
Ciljevi: Cilj ovog istraživanja bio je ispitati hormonski status štitne žlijezde u bolesnika kojima je učinjena dijagnostička biopsija bubrega te analizirati postoji li razlika u hormonskom statusu ovisno o indikaciji za biopsiju ili patohistološkoj dijagnozi. Dodatni ciljevi bili su usporediti hormonski status s ekskrecijskom funkcijom bubrega, kao i s razinom vitamina D u bubrežnih bolesnika te usporediti hormonski status s proteinurijom. Materijali i metode: U ovo retrospektivno presječno istraživanje uključeno je ukupno 89 bolesnika podijeljenih u pet skupina ovisno o indikaciji za dijagnostičku biopsiju nativnog bubrega (nefrotski sindrom, nefritički sindrom, kronična azotemija, brzoprogresivni glomerulonefritis, sindrom eritrociturije i proteinurije). Iz medicinske dokumentacije za svakog bolesnika analizirali su se parametri od interesa: dob, spol, visina, težina, anamneza ranije bolesti i terapije štitne žlijezde. Rutinski su se prije biopsije učinili laboratorijski nalazi: hemoglobin, kreatinin, eGFR, proteinurija, eritrociturija (da/ne), albumin u serumu, vitamin D, kolesterol, TSH, fT4, fT3, anti-TPO, anti-Tg. Za svakog je bolesnika učinjena svjetlosna i imunofluorescentna mikroskopija te je dobivena patohistološka dijagnoza. Rezultati: Najviše vrijednosti TSH zabilježene su u skupini ispitanika s BPGN-om i nefrotskim sindromom te najniže vrijednosti fT4 u skupini nefrotskog sindroma. Najniže vrijednosti TSH zabilježene su u skupini s kroničnom azotemijom, najviše vrijednosti fT3 u skupini eritrociturije i proteinurije, a najviše vrijednosti fT4 u skupini BPGN-a. eGFR nije korelirala s vrijednosti TSH, ali je korelirala s fT3, P=0,001 (Rho=0,404) i fT4, P=0,008 (Rho= -0,327). Vrijednost proteinurije pokazala je pozitivni trend korelacije s vrijednosti TSH, P=0,081 (Rho=0,193), odnosno obrnutu korelaciju s vrijednosti fT4, P<0,001 (Rho= -0,432), dok je za fT3 pokazana pozitivna korelacija, P=0,019 (Rho=0,301). Vrijednosti albumina i vitamina D negativno su korelirale s vrijednosti TSH, P=0,042 (Rho= -0,225), odnosno P=0,091 (Rho= -0,199), a pozitivno s vrijednostima slobodnih hormona, svi P<0,05. Najviše vrijednosti TSH izmjerene su u skupini s membranskom nefropatijom, a najniže vrijednosti TSH u ispitanika s bolesti lakih lanaca. Najniže vrijednosti fT3 bile su u ispitanika sa SLE-om, a najviše u ispitanika s IgA vaskulitisom. Ispitanici s HUS/TTP-om imali su najniže vrijednosti fT4, a oni s pauciimunim glomerulonefritisom najviše. Zaključci: Skupine ispitanika razlikovale su se po vrijednostima TSH i fT4, dok za vrijednosti fT3 nije pronađena statistički značajna razlika ovisno o indikaciji za biopsiju. Nije pronađena statistički značajna razlika u vrijednostima TSH, fT3 i fT4 s obzirom na patohistološku dijagnozu.Objectives: The primary goal of this study was to assess thyroid hormonal status in patients undergoing diagnostic kidney biopsy and to determine whether there is a difference in hormonal status based on the indication for biopsy or pathohistological diagnosis. Additional objectives included comparing thyroid function with renal excretory function, as well as with vitamin D levels in patients with kidney disease, and comparing thyroid hormonal status with proteinuria. Materials and methods: This retrospective cross-sectional study included a total of 89 patients divided into five groups depending on the indication for diagnostic biopsy of the native kidney (nephrotic syndrome, nephritic syndrome, chronic azotemia, rapidly progressive glomerulonephritis, erythrocyturia and proteinuria syndrome). The following parameters of interest were analyzed from the medical records for each patient: age, sex, height, weight, history of previous diseases, and thyroid therapy. Routine laboratory findings were performed before biopsy: hemoglobin, creatinine, eGFR, proteinuria, erythrocyturia (yes/no), serum albumin, vitamin D, cholesterol, TSH, fT4, fT3, anti-TPO, anti-Tg. Light and immunofluorescence microscopy were performed for each patient and a pathohistological diagnosis was obtained. Results: The highest TSH values were recorded in the group of subjects with BPGN and nephrotic syndrome, and the lowest fT4 values in the nephrotic syndrome group. The lowest TSH values were recorded in the group with chronic azotemia, the highest fT3 values in the group with erythrocyturia and proteinuria, and the highest fT4 values in the BPGN group. eGFR did not correlate with TSH values, but it correlated with fT3, P=0.001 (Rho=0.404) and fT4, P=0.008 (Rho= -0.327). The value of proteinuria showed a positive trend of correlation with the value of TSH, P=0.081 (Rho=0.193), an inverse correlation with the value of fT4, P<0.001 (Rho= -0.432), while a positive correlation was shown for fT3, P=0.019 (Rho=0.301). Albumin and vitamin D values correlated negatively with TSH values, P=0.042 (Rho= -0.225) and P=0.091 (Rho= -0.199), but positively with free hormone values, all P<0.05. The highest TSH values were measured in the group with membranous nephropathy, and the lowest TSH values in subjects with light chain deposition disease. The lowest fT3 values were in subjects with SLE, and the highest in subjects with IgA vasculitis. Subjects with HUS/TTP had the lowest fT4 values, and those with pauci-immune glomerulonephritis had the highest values. Conclusions: The groups of subjects differed in terms of TSH and fT4 values, while no statistically significant difference was found for fT3 values depending on the indication for biopsy. No statistically significant difference was found in the values of TSH, fT3, and fT4 considering the pathohistological diagnosis
Comparison of corneal pachymetry values measured by specular endothelial microscopy and Scheimpflug-based corneal topography in preoperative evaluation of patients undergoing cataract surgery by phacoemulsification
Ciljevi: Cilj istraživanja bio je usporediti rezultate mjerenja debljine rožnice (pahimetrije) dobivene spekularnom endotelnom mikroskopijom i kornealnom topografijom korištenjem Scheimpflug kamere kod bolesnika u prijeoperacijskoj obradi za operaciju mrene fakoemulzifikacijom. Dodatni cilj bio je utvrditi koja metoda pruža pouzdanije i klinički korisnije podatke za planiranje kirurškog zahvata i usporediti vrijednosti debljine rožnice izmjerene u najtanjoj točki i u središtu zjenice dobivene kornealnom topografijom na principu Scheimpflug kamere. Ispitanici i metode: Istraživanje je provedeno kao presječna studija u Klinici za očne bolesti KBC-a Split tijekom razdoblja od veljače do lipnja 2025. godine. U istraživanju su sudjelovali bolesnici upućeni na rutinsku prijeoperacijsku obradu u sklopu pripreme za operaciju mrene metodom fakoemulzifikacije. Mjerenje debljine rožnice provedeno je pomoću dviju dijagnostičkih metoda. Prva je spekularna endotelna mikroskopija (Tomey EM-4000), koja omogućuje mjerenje središnje debljine rožnice (CCT) analizom reflektiranih svjetlosnih valova, uz prikaz i ultrazvučno izmjerene debljine rožnice (CCT(US)), te morfoloških parametara endotela: gustoće stanica (CD), koeficijenta varijacije veličine (CV) i udjela šesterokutnih stanica (6A). Druga metoda je kornealna topografija na principu Scheimpflug kamere (Pentacam HR, Oculus), kojom se dobivaju detaljne tomografske i pahimetrijske mape. Rezultati: Rezultati su pokazali statistički značajnu razliku u debljini rožnice između metoda (p < 0,001). Spekularna mikroskopija podcjenjivala je vrijednosti u odnosu na ultrazvučnu pahimetriju i Pentacam. Također je utvrđena statistički značajna razlika između debljine rožnice mjerene Pentacamom u najtanjoj točki i u središtu zjenice (p < 0,001). Nije utvrđena korelacija između dobi ispitanika i morfoloških parametara endotela (CD, CV, 6A). Zaključci: Pahimetrijske vrijednosti značajno se razlikuju između korištenih metoda i mjernih točaka. Spekularna mikroskopija nije pokazala prednost u predviđanju postoperativnih ishoda u odnosu na Pentacam, što potvrđuje važnost standardizacije mjernih metoda u prijeoperacijskoj procjeni rožnice.Objectives: The aim of this study was to compare corneal thickness (pachymetry) measurements obtained using specular endothelial microscopy and corneal topography based on Scheimpflug imaging in patients undergoing preoperative assessment for cataract surgery via phacoemulsification. An additional objective was to determine which method provides more reliable and clinically useful data for surgical planning and to compare corneal thickness values measured at the thinnest point and at the pupil center using Scheimpflug-based corneal topography. Subjects and methods: This cross-sectional study was conducted at the Department of Ophthalmology, University Hospital of Split, from February to June 2025. The study included patients referred for routine preoperative assessment prior to cataract surgery by phacoemulsification. Corneal thickness was measured using two diagnostic methods. The first was specular endothelial microscopy (Tomey EM-4000), which measures central corneal thickness (CCT) based on reflected light waves, and also displays corneal thickness obtained by ultrasound pachymetry (CCT(US)), along with endothelial morphological parameters: cell density (CD), coefficient of variation in cell size (CV), and percentage of hexagonal cells (6A). The second method was corneal topography using a Scheimpflug camera (Pentacam HR, Oculus), which provides detailed tomographic and pachymetric maps. Results: A statistically significant difference in corneal thickness was observed between the two methods (p < 0.001). Specular microscopy underestimated values compared to both ultrasound pachymetry and Pentacam. A statistically significant difference was also found between corneal thickness measured at the thinnest point and at the pupil center using Pentacam (p < 0.001). No correlation was found between patient age and endothelial morphological parameters (CD, CV, 6A). Conclusions: Pachymetric values differ significantly between the methods used and the measurement locations. Specular microscopy did not show an advantage over Pentacam in predicting postoperative outcomes, highlighting the importance of standardizing measurement techniques in the preoperative assessment of the cornea
Efficacy and tolerability of cemiplimab in the treatment of metastatic cutaneous squamous cell carcinoma
Ciljevi: Imunoterapija metastatskog planocelularnog karcinoma kože cemiplimabom, anti- PD1 protutijelom, predstavlja terapiju izbora u prvoj liniji liječenja. Istraživali smo kliničke karakteriste bolesnika s metastatskim PCC koji su u 1. liniji liječeni cemiplimabom na Klinici za onkologiju i radioterapiju KBC Split. Analizirali smo patohistološke osobitosti planocelularnog karcinoma kože kod inicijalne dijagnoze bolesti te učinkovitost i podnošljivost liječenja cemiplimabom. Bolesnici i metode: Retrospektivno su sakupljeni i obrađeni podaci iz povijesti bolesti 10 bolesnika s metastatskim karcinomom kože liječenih cemiplimabom u razdoblju od 1. svibnja 2020. do 1. siječnja 2025. godine. Podatci su uključivali dob, spol, prateću komorbidnost, osobnu i obiteljsku anamnezu na zloćudne bolesti, inicijalni stadij bolesti i patohistološke osobitosti PCC, nuspojave i ishode liječenja definirane kroz stopu odgovora, trajanje liječenja metastatske bolesti cemiplimabom te medijan PFS i OS. Rezultati: Medijan životne dobi bolesnika s metastatskim PCC u času dijagnoze iznosio je 74 godine. U istraživanje je uključeno 9 bolesnika i 1 bolesnica. Pet bolesnika je imalo prethodno iskustvo zloćudne bolesti kože. Od prateće komorbinosti prednjačila je arterijska hipertenzija i šećerna bolest tipa II. Kod inicijalne dijagnoze podjednako je bila zastupljena lokalna i lokoregionalna resektabilna/neresektabilna bolest, te je samo 1 bolesnik bio s hematogenom diseminacijom. Medijan dubine invazije kože iznosio je 8 mm, s prisutnom ulceracijom (70%) i satelitskim lezijama (40%). Tri od 6 bolesnika s pozitivnim limfnim čvorovima (50%) imalo je perikapsularnu infiltraciju. Svi bolesnici su u trenutku potvrde metastatske bolesti liječeni cemiplimabom (100%). Medijan trajanja liječenja cemiplimabom iznosio je 3 mjeseca. Objektivna stopa odgovora iznosila je 50% (40% PR, 10% SD). Medijan PFS-a iznosio je 3 mjeseca, a medijan OS-a 21 mjesec. Cemiplimab je imao prihvatljiv toksični profil. Od svih prijavljenih nuspojava prednjačila je anemija (70%) i tireotoksičnost (20%). Dvoje od 4 bolesnika (50%) s iskustvom progresije na cemiplimab liječeno je kemoterapijom temeljenoj na platini. Na kraju analize, 5 bolesnika je živo s bolesti i liječe se (50%), a petero bolesnika je preminulo (50%). Zaključak: Rezultati naše analize usporedivi su rezultatima studije faze II sa cemiplimabom. Za relevantniju procjenu učinkovitosti i podnošljivosti cemiplimaba potrebno je pratiti i analizirati veći broj bolesnika kroz duže razdoblje.Objectives: Immunotherapy of metastatic cutaneous squamous cell carcinoma with cemiplimab, an anti-PD1 antibody, represents the therapy of choice in first-line treatment. We investigated the clinical characteristics of patients with metastatic cSCC who were treated with cemiplimab in first-line therapy at the Department of Oncology and Radiotherapy of University Hospital of Split. We analyzed the histopathological features of cutaneous squamous cell carcinoma at initial disease diagnosis and the efficacy and tolerability of cemiplimab treatment. Patients and Methods: Data from medical records of 10 patients with metastatic cutaneous carcinoma treated with cemiplimab were retrospectively collected and processed in the period from May 1, 2020, to January 1, 2025. Data included age, sex, accompanying comorbidities, personal and family history of malignant diseases, initial disease stage and histopathological features of cSCC, side effects and treatment outcomes defined through response rate, duration of metastatic disease treatment with cemiplimab, as well as PFS and OS. Results: The median age of patients with metastatic cSCC at the time of diagnosis was 74 years. The study included 9 male patients and 1 female patient. Five patients had previous experience with malignant skin disease. Among accompanying comorbidities, arterial hypertension and type II diabetes mellitus predominated. At initial diagnosis, local and locoregional resectable/unresectable disease were equally represented, and only 1 patient had hematogenous dissemination. The median depth of skin invasion was 8 mm, with present ulceration (70%) and satellite lesions (40%). Three of 6 patients with positive lymph nodes (50%) had extracapsular extension. All patients were treated with cemiplimab at the time of confirmed metastatic disease (100%). The median duration of cemiplimab treatment was 3 months. The objective response rate was 50% (40% PR, 10% SD). Median PFS was 3 months, and median OS was 21 months. Cemiplimab had an acceptable toxicity profile. Among all reported adverse events, anemia (70%) and thyrotoxicity (20%) predominated. Two of 4 patients (50%) with disease progression on cemiplimab were treated with platinum-based chemotherapy. At the end of the analysis, 5 patients were alive with disease and receiving treatment (50%), and five patients had died (50%). Conclusion: The results of our analysis are comparable to the results of the phase II study with cemiplimab. For a more relevant assessment of cemiplimab efficacy and tolerability, it is necessary to monitor and analyze a larger number of patients over a longer period of time
Inovacije : Splitska estetska akademija – SEA: Nova paradigma mentorstva u estetskoj medicini
Vitamin D levels in children and adolescents with Hashimoto's thyroiditis
Cilj: Prikazati kliničko-demografske karakteristike u djece i adolescenata s Hashimotovim tireoiditisom, odrediti koncentracije vitamina D te ispitati povezanost vitamina D s imunološkim markerima i ultrazvučnim promjenama štitne žlijezde. Metode: Prospektivno istraživanje obuhvatilo je 63 ispitanika (52 djevojčice, 11 dječaka; prosječna dob 13,41 ± 3,12 godina) liječenih na Klinici za dječje bolesti KBC Split od rujna 2022. do svibnja 2025. Standardni postupci uključivali su anamnezu, antropometriju (visina, težina, ITM), biokemijske analize (TSH, FT4, FT3, anti-TPO, anti-Tg, 25-OHD) te ultrazvuk štitne žlijezde (klasificiran u 4 skupine prema stupnju heterogenosti i ehogenosti). Rezultati: Prosječna razina vitamina D iznosila je 50,06 ± 18,68 nmol/L Značajna negativna korelacija pronađena je između 25-OHD i anti-TPO antitijela (r = −0,258; p = 0,041), ali ne i s anti-Tg (r = −0,132; p = 0,301). Nije uočena značajna razlika u 25-OHD između skupina s blažim (skupina 1–2: 52,73 ± 19,1 nmol/L) i izraženijim ultrazvučnim promjenama (skupina 3–4: 46,94 ± 18 nmol/L; p = 0,149). Zaključak: Istraživanje je pokazalo da niže razine vitamina D kod djece i adolescenata s Hashimotovim tireoiditisom koreliraju s višim razinama autoimunih antitijela, što ukazuje na povezanost između nedostatka vitamina D i autoimune aktivnosti štitne žlijezde. Iako postoje jasni pokazatelji povezanosti između niskih razina vitamina D i povećane autoimunosti, potrebna su dodatna istraživanja za bolje razumijevanje mehanizama, određivanje optimalne doze i trajanja suplementacije te identifikaciju pacijenata kojima bi to najviše koristilo.Objective: To present the clinical and demographic characteristics of children and adolescents with Hashimoto’s thyroiditis, determine vitamin D concentrations, and examine the association of vitamin D with immunological markers and ultrasound changes of the thyroid gland. Methods: This prospective study included 63 participants (52 girls, 11 boys; mean age 13.41 ± 3.12 years) treated at the Pediatric Clinic, University Hospital Split, from September 2022 to May 2025. Standard procedures included medical history, anthropometric measurements (height, weight, BMI), biochemical analyses (TSH, FT4, FT3, anti-TPO, anti-Tg, 25-OHD), and thyroid ultrasound (classified into 4 groups based on degree of heterogeneity and echogenicity). Results: The average vitamin D level was 50.06 ± 18.68 nmol/L. A significant negative correlation was found between 25-OHD and anti-TPO antibodies (r = −0.258; p = 0.041), but not with anti-Tg (r = −0.132; p = 0.301). No significant difference in 25-OHD levels was observed between groups with milder (groups 1–2: 52.73 ± 19.1 nmol/L) and more pronounced ultrasound changes (groups 3–4: 46.94 ± 18 nmol/L; p = 0.149). Conclusion: Research has shown that lower levels of vitamin D in children and adolescents with Hashimoto's thyroiditis correlate with higher levels of autoimmune antibodies, indicating a connection between vitamin D deficiency and autoimmune thyroid activity. Although there are clear indicators of an association between low vitamin D levels and increased autoimmunity, further research is needed to better understand the mechanisms, determine the optimal dosage and duration of supplementation, and identify the patients who would benefit the most