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Pathohistological and clinical characteristics of primarily surgically treated breast cancers in the Republic of Croatia in 2021
No full textCilj istraživanja: Cilj istraživanja bio je analizirati patohistološke i kliničke osobitosti bolesnika s karcinomom dojke koji su primarno kirurški liječeni u Republici Hrvatskoj u 2021. godini, kao i raspodjelu tipa i broja kirurških zahvata po ustanovama uz usporedbu dobivenih rezultata s prethodno objavljenim epidemiološkim podacima na temelju sličnih istraživanja u Republici Hrvatskoj i drugim državama. Materijali i metode: U ovo istraživanje su bile uključene 2230 ispitanice s dijagnozom invazivnog karcinoma dojke koje su primarno kirurški liječene. Kao izvor podataka korišten je Patološki registar karcinoma dojke koji vodi Sekcija za dojku Hrvatskog društva patologije i citologije. U ovoj retrospektivnoj studiji analizirani su slijedeći parametri: ustanova u kojoj je proveden kirurški zahvat, dob pri postavljanju dijagnoze, tip operativnog zahvata, veličina tumora, fokalnost i bilateralnost promjena, histološki podtip, histološki gradus, status prediktivnih biomarkera, imunofenotip tumora te broj izoliranih i zahvaćenih limfnih čvorova. Rezultati: U Republici Hrvatskoj su u 2021. godini primarno kirurški liječene 2230 bolesnice s karcinomom dojke. Liječenje se provodilo u 22 različite ustanove, a u pet ustanova urađeno je više od 100 operacija. Najčešće provođeni kirurški zahvat bila je kvadrantektomija (48.1%). U najvećim ustanovama postojale su statistički značajne razlike u odabiru kirurškog zahvata. U Kliničkom bolničkom centru Split postojao je statistički značajno veći udio klasičnih mastektomija (62.9% p<0.001) i supkutanih mastektomija (14.6%; p<0.001) u odnosu na druge ustanove. Klinički bolnički centar Rijeka (85.2%; p<0.001) i KZT (59.9%; p<0.001) pokazali su statistički značajno veći udio kvadrantektomija u odnosu na ostale ustanove, dok je u Kliničkom bolničkom centru Zagreb (18.3%; p<0.001) postojao je statistički značajno veći udio supkutanih mastektomija u odnosu na druge centre. U Kliničkom bolničkom centru Osijek (50.3%; p<0.001) postojao je statistički značajno veći udio tumorektomija u odnosu na ostale centre. Prosječna dob ispitanica bila je 62 godine te je u skupini od 60 do 69 zabilježen najveći broj oboljelih s udjelom od 29.7%. Prosječna veličina tumora bila je 1.87 cm, najzastupljeniji su bili tumori u T1c kategoriji s udjelom od 39.8%. Multiple tumore u istoj dojci je imalo 13.6% ispitanica, a u 0.9% slučajeva radilo se o difuzno infiltrirajućem karcinomu dojke. U 4.6% slučajeva postojao pronađen je i sinkroni karcinom druge dojke. Najčešći histološki podtip je bio invazivni karcinom NOS s udjelom od 78.6%, dok su prema imunofenotipu na prvom mjestu bili luminalni B karcinomi s udjelom od 49.3%, a najčešći histološki gradus bio je gradus 2. ER su bili pozitivni u 83.7%, PR bili pozitivni u 74.1% slučajeva, a HER2 status je bio pozitivan u 14.9% (332) slučajeva. Prosječna vrijednost Ki-67 proliferacijskog biljega bila je 29.7%. SLNB provedena je u 55.3%, a disekcija aksile u 43.3% ispitanica. Zaključak: Postoje statistički značajne razlike u odabiru kirurškog zahvata između ustanova u Republici Hrvatskoj. Kliničko-patološke karakteristike tumora u ovom istraživanju uglavnom se slažu sa statistikom i epidemiološkom podacima drugih država i studijama prethodnih godina za Republiku Hrvatsku.Research objective: The aim of this study was to analyze the pathohistological and clinical characteristics of patients with breast cancer who underwent primary surgical treatment in the Republic of Croatia in 2021, as well as to examine the distribution of the types and number of surgical procedures across medical institutions. The results were compared with previously published epidemiological data based on similar studies conducted in Croatia and other countries. Materials and methods: This study included 2,230 female patients diagnosed with invasive breast cancer who underwent primary surgical treatment. The source of data was the Breast Cancer Pathology Registry maintained by the Breast Section of the Croatian Society of Pathology and Cytology. In this retrospective study, the following parameters were analyzed: the institution where the surgical procedure was performed, age at diagnosis, type of surgical procedure, tumor size, focality and bilaterality of the lesions, histological subtype, histological grade, status of predictive biomarkers, tumor immunophenotype, and the number of isolated and affected lymph nodes. Results: In the Republic of Croatia, a total of 2,230 patients with breast cancer underwent primary surgical treatment in 2021. Treatment was carried out across 22 different medical institutions, with more than 100 surgeries performed in five of them. The most commonly performed surgical procedure was quadrantectomy (48.1%). Statistically significant differences in the choice of surgical procedure were observed among the largest institutions. At the University Hospital Center Split, there was a statistically significantly higher proportion of classical mastectomies (62.9%; p<0.001) and subcutaneous mastectomies (14.6%; p<0.001) compared to other centers. The University Hospital Center Rijeka (85.2%; p<0.001) and the Clinic for Tumors (KZT) (59.9%; p<0.001) reported significantly higher proportions of quadrantectomies, while the University Hospital Center Zagreb had a significantly higher proportion of subcutaneous mastectomies (18.3%; p<0.001). In the University Hospital Center Osijek, a significantly higher proportion of tumorectomies was observed (50.3%; p<0.001) compared to other centers. The average age of the patients was 62 years, with the highest incidence recorded in the 60–69 age group, accounting for 29.7% of all cases. The mean tumor size was 1.87 cm, with T1c tumors being the most prevalent (39.8%). Multiple tumors in the same breast were present in 13.6% of cases, while diffusely infiltrating breast cancer was identified in 0.9%. Synchronous cancer of the contralateral breast was found in 4.6% of patients. The most common histological subtype was invasive carcinoma of no special type (NST), accounting for 78.6% of cases. Based on immunophenotype, luminal B carcinomas were the most frequent (49.3%), and histological grade 2 was the most common grade observed. Estrogen receptors (ER) were positive in 83.7% of cases, progesterone receptors (PR) in 74.1%, while HER2 positivity was reported in 14.9% (332 cases). The average Ki-67 proliferation index was 29.7%. Sentinel lymph node biopsy (SLNB) was performed in 55.3% of patients, while axillary dissection was carried out in 43.3%. Conclusion: There are statistically significant differences in the choice of surgical procedures among medical institutions in the Republic of Croatia. The clinicopathological characteristics of tumors observed in this study are largely consistent with statistics and epidemiological data from other countries, as well as with findings from previous studies conducted in Croatia
Knowledge of Dental Medicine and Medical students at the University of Split regarding bisphosphonates and their oral complications
No full textCilj: Glavni cilj ovoga istraživanja je bio dobiti informacije od studenata Studija dentalne medicine i medicine Sveučilišta u Splitu o poznavanju činjenica vezanih uz bisfosfonate i njihovu primjenu te o njihovim oralnim nuspojavama. Materijali i metode: Istraživanje je provedeno pomoću anonimnog elektroničkog upitnika podijeljenog studentima 5. i 6. godine studija dentalne medicine i medicine Sveučilišta u Splitu tijekom ožujka 2025. godine. Upitnik se sastojao od 16 pitanja podijeljenih u tri cjeline: osnovni podaci, znanje o bisfosfonatima te stavovi. Usporedba između dviju skupina izvedena je Mann-Whitney U testom. Utjecaj prediktorskih varijabli poput vrste studija, godine studija i spola ispitanika ispitivan je višestrukom regresijskom analizom. Rezultati: U istraživanje je bilo uključeno 100 studenata Medicinskog fakulteta Sveučilišta u Splitu, 5. i 6. godina studija , od čega 54 studenata dentalne medicine i 46 studenata medicine. Rezultati istraživanja pokazali su da je znanje studenta o bisfosfonatima i njihovim oralnim nuspojavama na zavidnoj razini. Svih 100 studenata je točno prepoznalo indikacije bisfosfonatne terapije kao i nazive bisfosfonatnih lijekova. Komplikacije primjene bisfosfonatne terapije znalo je 93% studenata, dok je njih nešto manje, 86% znalo da su bisfosfonati antiresorptivni lijekovi. Studenti dentalne medicine su pokazali veće znanje u odnosu na studente medicine kada se radi o pravilnom postupanju s pacijentima na bisfosfonatnoj terapiji prije provođenja invazivnog dentalnog zahvata. Svi studenti dentalne medicine i 93% studenta medicine prepoznala su važnost odlaska na pregled kod doktora dentalne medicine prije početka bisfosfonatne terapije. Gotovo svi studenti su tijekom svog dosadašnjeg obrazovanja imali mogućnost steći znanja o bisfosfonatima, a također i izrazila želju za daljnim učenjem. Zaključak: Rezultati višestruke regresijske analize pokazali su da studenti dentalne medicine imaju statistički višu razinu znanja o bisfosfonatima i njihovim oralnim nuspojavama u odnosu na studente medicine. Unatoč tome, obje skupine studenata pokazale su zavidnu razinu znanja, što predstavlja važan temelj za daljnje profesionalno djelovanje te učinkovitiji pristup pacijentima, koji mora biti multidisciplinaran.Objective: The primary aim of this study was to assess the knowledge and awareness of students enrolled in the Dental Medicine and Medicine programs at the University of Split regarding bisphosphonate therapy, its clinical applications, and associated oral side effects. Materials and Methods: This research was conducted in March 2025 using an anonymous electronic questionnaire distributed to 5th- and 6th-year Dental Medicine and Medicine students at the University of Split. The questionnaire had 16 questions divided into three sections: demographic data, knowledge of bisphosphonates, and student attitudes. Data were analyzed using the STATISTICA 11.0 software package. Comparisons between the two groups were performed using the Mann-Whitney U test. At the same time, the influence of predictor variables such as study program, year of study, and gender was evaluated through multiple regression analysis. Results: 100 students from the University of Split School of Medicine participated in the study-54 from the Dental Medicine program and 46 from the Medicine program. Overall, the students demonstrated a high level of knowledge regarding bisphosphonates and their oral complications. All participants correctly identified the indications for bisphosphonate therapy and the names of bisphosphonate drugs. Complications related to bisphosphonate use were recognized by 93% of students, and 86% correctly identified bisphosphonates as antiresorptive agents. Dental Medicine students showed a higher level of knowledge than Medicine students, particularly concerning appropriate clinical management of patients undergoing invasive dental procedures while on bisphosphonate therapy. All Dental Medicine students and 93% of Medicine students recognized the importance of dental examination before initiating bisphosphonate treatment. Nearly all students reported having received education on bisphosphonates during their studies and expressed a desire for further learning on the subject. Conclusion: Dental Medicine students demonstrated a statistically higher level of knowledge about bisphosphonates and their oral side effects than Medical students. Nonetheless, both groups showed a commendable level of understanding, which provides a strong foundation for future clinical practice and supports the need for a multidisciplinary approach in managing patients undergoing bisphosphonate therapy
Analysis of tumor marker values in hospitalized patients with diabetes mellitus
No full textCiljevi: Cilj istraživanja je analizirati tumorske biljege u hospitaliziranih bolesnika sa šećernom bolesti te utvrditi povezanost tih biljega s regulacijom glikemije, prisustvom kroničnih komplikacija šećerne bolesti, farmakoterapijom te nalazima radiološke dijagnostičke obrade. Materijali i metode: U presječno istraživanje uključeno je 106 bolesnika sa šećernom bolesti koji su hospitalizirani na Zavodu za endokrinologiju, dijabetes i bolesti metabolizma, Kliničkog bolničkog centra Split. Podatci su prikupljeni iz bolničkog informacijskog sustava i obuhvaćali su antropometrijske mjere, laboratorijske vrijednosti HbA1c, jetrenih enzima, eGFR i vrijednosti tumorskih biljega (CEA, CA 19-9, AFP i PSA), podatke o prisustvu dijabetičkih komplikacija i farmakoterapiji. Rezultati: Najveći udio hospitaliziranih bolesnika sa šećernom bolesti nema povišene vrijednosti tumorskih biljega, koji su prisutni u 38 % ispitanika. Nije utvrđena značajna povezanost između radiološki potvrđene maligne bolest i prisutnosti povišenih tumorskih biljega CEA (P = 0,060), CA 19-9 (P = 0,443), AFP (P = 0,458). Vrijednost HbA1c nije bila povezana s brojem povišenih vrijednosti tumorskih biljega (P = 0,075). Nije bilo značajne razlike između skupine ispitanika koji su imali povišene tumorske biljege u odnosu na skupinu ispitanika koja nije imala povišene vrijednosti tumorskih biljega u vrijednosti HbA1c (P = 0,075) i ITM-a (P = 0,081). Komplikacije šećerne bolesti bile su zabilježene u 60 % slučajeva. Skupina ispitanika koji su imali barem jednu komplikaciju šećerne bolesti, imala je statistički značajno češće povišen barem jedan tumorski marker u odnosu na skupinu ispitanika bez komplikacija šećerne bolesti (P = 0,004). Najčešća terapija je bila inzulinska terapija u 91 % ispitanika i nije utvrđena značajna razlika u inzulinskoj terapiji (P = 0,468) između skupina bolesnika obzirom na prisustvo povišenih tumorskih biljega. Zaključak: Najveći udio hospitaliziranih bolesnika sa šećernom bolesti nema povišene vrijednosti tumorskih biljega i regulacija glikemije prema vrijednostima HbA1c nije povezana s ukupnim brojem povišenih tumorskih biljega. Nije utvrđena značajna povezanost između radiološki potvrđene maligne bolesti i povišenih tumorskih biljega. Hospitalizirani bolesnici sa šećernom bolesti koji su imali povišene tumorske biljege imali su češće komplikacije šećerne bolesti, a nisu se razlikovali u vrijednostima HbA1c, ITM-e i primjeni inzulinske terapije.Objectives: The aim of this study is to analyze tumor markers in hospitalized patients with diabetes mellitus and to determine their association with glycemic control, the presence of chronic diabetic complications, pharmacotherapy, and findings from radiological diagnostic procedures. Subjects and procedures: A total of 106 patients with diabetes mellitus who were hospitalized at the Department of Endocrinology, Diabetes, and Metabolic Diseases of the University Hospital of Split were included in this cross-sectional study. Data were collected from the hospital information system and encompassed anthropometric measurements, laboratory parameters including HbA1c, liver enzymes, estimated glomerular filtration rate (eGFR), and tumor marker levels (CEA, CA 19-9, AFP, and PSA), as well as information on the presence of diabetic complications and pharmacotherapy. Results: The majority of hospitalized patients with diabetes mellitus did not exhibit elevated tumor marker levels, which were present in 38 % of the study population. No statistically significant association was found between radiologically confirmed malignant disease and elevated levels of the tumor markers CEA (P = 0.060), CA 19-9 (P = 0.443), or AFP (P = 0.458). Glycated hemoglobin (HbA1c) levels were not significantly associated with the number of elevated tumor markers (P = 0.075). Furthermore, there was no statistically significant difference in HbA1c levels (P = 0.075) or body mass index (BMI) (P = 0.081) between the group with elevated tumor markers and the group without elevated marker values. Diabetic complications were documented in 60 % of cases. Patients with at least one diabetic complication had a significantly higher prevalence of elevated tumor marker levels compared to those without complications (P = 0.004). Insulin therapy was the most frequently used treatment, administered in 91 % of patients, and no statistically significant difference in insulin therapy was observed between groups stratified by the presence of elevated tumor markers (P = 0.468). Conclusions: The majority of hospitalized patients with diabetes mellitus did not exhibit elevated tumor marker levels, and glycemic control, as assessed by HbA1c values, was not associated with the total number of elevated tumor markers. No statistically significant association was found between radiologically confirmed malignant disease and elevated tumor marker levels. Hospitalized patients with diabetes mellitus who had elevated tumor markers more frequently presented with diabetic complications, while no significant differences were observed in HbA1c levels, body mass index (BMI), or the use of insulin therapy between patients with and without elevated tumor markers
Utjecaj klimatskih čimbenika na stopu smrtnosti hospitaliziranih bolesnika u Splitu, Hrvatska
No full textObjective: This cross-sectional, retrospective study aimed to examine the relationship between daily climatic factors and in-hospital mortality in Split, Croatia. Specific objectives included to examine the relationship between climatic factors and hospital death rates, to identify seasonal or weather related patterns in hospital Mortality and to determine whether extreme weather events like heat waves, correspond with peaks of hospital death rates. Materials and Methods: This study included data on 1582 in-hospital death recorded between January and November 2024. Data were collected from hospital death records and paired with daily meteorological variables obtained from the Croatian Meteorological and Hydrological Service. Descriptive Statistics, Kolmogorov-Smirnov-Test, t-test, Pearson correlation coefficients and multiple linear regression were used to analyse associations between weather conditions and mortality. Results: The Majority of deaths occurred among patients aged 65 and older with respiratory insufficiency, sepsis and pneumonia being the most common cause of death. A clear seasonal pattern in mortality was observed with peaks in January, July and October. No statistically significant increase in mortality was observed during heatwaves. However average daily temperature showed a weak but significant positive association with total daily death, while maximum temperature had an inverse relationship. In individuals aged 80 and above, higher temperatures were slightly associated with lower daily mortality. Other weather variables including humidity and wind speed, showed no consistent association with death rates. Conclusion: In-Hospital mortality in Split, was highest among elderly patients, particularly during cold and transitional months. While heat waves did not significantly impact mortality, temperature showed some influence on death rates, especially in the oldest age group. These finding suggest that cold- related health risks remain more critical in this setting than heat exposure. Improved hospital data collection and expanded research on environmental health impacts are recommended to guide future public health strategies.Ciljevi: Ova presječna, retrospektivna studija imala je za cilj ispitati povezanost između dnevnih klimatskih čimbenika i smrtnosti hospitaliziranih bolesnika u Splitu, Hrvatska. Specifični ciljevi uključivali su ispitivanje odnosa između klimatskih čimbenika i bolničke smrtnosti, prepoznavanje sezonskih ili vremenski povezanih obrazaca u bolničkoj smrtnosti te utvrđivanje postoji li povezanost između ekstremnih vremenskih pojava, poput toplinskih valova, i porasta broja bolničkih smrti. Materijali i metode: Studija je obuhvatila podatke o 1582 bolničke smrti zabilježene između siječnja i studenog 2024. godine. Podatci su prikupljeni iz bolničkih evidencija o smrtnosti i upareni s dnevnim meteorološkim varijablama dobivenima od Državnog hidrometeorološkog zavoda. Za analizu povezanosti između vremenskih uvjeta i smrtnosti korišteni su deskriptivna statistika, Kolmogorov-Smirnov test, t-test, Pearsonovi koeficijenti korelacije te višestruka linearna regresija. Rezultati: Većina umrlih bili su pacijenti stariji od 65 godina, pri čemu su respiratorna insuficijencija, sepsa i upala pluća bili najčešći uzroci smrti. Uočen je jasan sezonski obrazac smrtnosti, s vrhuncima u siječnju, srpnju i listopadu. Nije zabilježen statistički značajan porast smrtnosti tijekom toplinskih valova. Međutim, prosječna dnevna temperatura pokazala je slabu, ali značajnu pozitivnu povezanost s ukupnom dnevnom smrtnošću, dok je maksimalna temperatura imala obrnuti odnos. Kod osoba starijih od 80 godina, više temperature bile su blago povezane s nižom dnevnom smrtnošću. Ostale meteorološke varijable, uključujući vlagu i brzinu vjetra, nisu pokazale konzistentnu povezanost sa stopama smrtnosti. Zaključci: Bolnička smrtnost u Splitu bila je najveća među starijim bolesnicima, osobito tijekom hladnih i prijelaznih mjeseci. Iako toplinski valovi nisu imali značajan utjecaj na smrtnost, temperatura je pokazala određeni utjecaj, osobito u najstarijoj dobnoj skupini. Ovi rezultati upućuju na to da su zdravstveni rizici povezani s hladnoćom u ovom kontekstu značajniji od onih povezanih s toplinom. Preporučuje se poboljšanje prikupljanja bolničkih podataka i proširenje istraživanja o utjecaju okolišnih čimbenika na zdravlje radi bolje usmjerenih javnozdravstvenih strategija
Psychophysiological stress response in divers with autonomous diving equipment
No full textUvod: Ronjenje uz autonomni aparat za podvodno disanje (engl. self-contained underwater breathing apparatus (SCUBA)) predstavlja izazov za psihofiziološku prilagodbu zbog visokih tlakova, promjena temperature, povećanog gubitka topline, smanjene vidljivosti i učinaka disanja plinova pod tlakom, što narušava fiziološku homeostazu organizma. Ovi uvjeti, zajedno s psihološkim stresorima kao što su anksioznost i senzorna disintegracija, mogu uzrokovati disregulaciju emocija i fizioloških reakcija. Neprilagođene kognitivne strategije, uključujući katastrofiziranje i zabrinutost, dodatno povećavaju stres i rizik od razvoja anksioznosti i depresije, pritom narušavajući emocionalnu regulaciju. Aktivacija negativnih automatskih misli (NAM) pokreće neurobiološke mehanizme stresa, uključujući povećanu aktivnost HHN osi i promjene cirkadijskog ritma lučenja kortizola, što može narušiti homeostazu, dovesti do promjena u glikemijskom profilu, varijabilnosti krvnog tlaka te oscilacija u srčanoj frekvenciji, povećavajući rizik od psihofizioloških disfunkcija tijekom i nakon ronjenja. Metode: Istraživanje je obuhvatilo dvije studije s ukupno 81 roniocem, uključujući 14 vojnih ronilaca. Sudionici su prije i nakon ronjenja ispunili validirane upitnike: Ljestvica depresivne anksioznosti i stresa (engl. Depression Anxiety Stress Scales (DASS)), Upitnik anksioznosti kao osobine ličnosti i anksioznosti kao stanja (engl. State Trait Anxiety Inventory (STAI)). Prvo istraživanje validiralo je pouzdanost i valjanost novo kreiranih upitnika (Ljestvica pozitivnih i negativnih emocija i Upitnik NAM prije ronjenja) te ispitivalo razlike u negativnim mislima, emocijama i razinama kortizola između vojnih i rekreativnih ronilaca. Istražena je povezanost kortizola s negativnim mislima i emocijama te njihov utjecaj na razine kortizola, anksioznosti i depresivnosti prije i nakon ronjenja. Drugo istraživanje analiziralo je kardiovaskularni stres (arterijski tlak, srčana frekvencija) i promjene razine glukoze prije i nakon ronjenja u odnosu na psihološke pokazatelje stresa kod ronilaca. Rezultati: Negativne emocije značajno su utjecale na psihofiziološke odgovore tijekom ronjenja, dok su NAM imale ograničen učinak na fiziološke promjene, što sugerira da emocije imaju jači utjecaj na reakcije tijela od kognitivnih procesa povezanih s prijetnjom ili neuspjehom. Profesionalni ronioci zadržali su stabilnije razine kortizola u odnosu na rekreativne, što ukazuje na bolju prilagodbu stresnim uvjetima. Porast dijastoličkog arterijskog tlaka, uz stabilnost sistoličkog, potvrđuje otpornost kardiovaskularnog sustava na promjene hidrostatskog pritiska. Smanjenje srčane frekvencije i razine glukoze nakon ronjenja ukazuje na učinkovitu fiziološku adaptaciju organizma i smanjenje metaboličkih potreba. Psihološki učinci uključuju smanjenje stresa i anksioznosti te pad negativnih emocija, neovisno o NAM, sugerirajući pozitivan učinak ronjenja. NAM nisu značajno utjecale na fiziološke parametre, potvrđujući stabilnost odgovora organizma. Validacija upitnika potvrdila je njihovu pouzdanost i primjenjivost za praćenje psihofizioloških promjena kod ronilaca, čineći ih korisnim alatima za buduća istraživanja i procjenu stresnih reakcija. Zaključak: Emocionalna regulacija ključna je za upravljanje psihofiziološkim odgovorima tijekom ronjenja, pri čemu negativne emocije snažnije utječu na fiziološke reakcije od NAM. Profesionalni ronioci, s boljom prilagodbom i stabilnijim razinama kortizola, pokazuju veću otpornost na stresne uvjete u usporedbi s rekreativnim roniocima, naglašavajući važnost iskustva i obuke. Smanjenje stresa, anksioznosti i negativnih emocija nakon ronjenja ukazuje na terapijski potencijal ove aktivnosti u poboljšanju emocionalne dobrobiti, neovisno o prisutnosti NAM. Validirani upitnici pokazali su visoku pouzdanost i primjenjivost za istraživanje psihofizioloških odgovora na stres kod ronilaca. Stabilnost fizioloških reakcija, unatoč negativnim mislima, naglašava potrebu za daljnjim istraživanjima o mehanizmima prilagodbe te razvoju strategija za smanjenje negativnih emocija i poboljšanje prilagodbe ronioca.Introduction: Diving with a self-contained underwater breathing apparatus (SCUBA) poses challenges in terms of psychophysiological adaptation due to high pressures, temperature changes, increased heat loss, reduced visibility, and the effects of breathing gases under pressure, all of which disrupt physiological homeostasis. These conditions, combined with psychological stressors such as anxiety and sensory disintegration, can lead to the dysregulation of emotions and physiological reactions. Inadequate cognitive strategies, including catastrophizing and worry, further increase stress and the risk of developing anxiety and depression, impairing emotional regulation. The activation of negative automatic thoughts (NAT) triggers neurobiological stress mechanisms, such as the increased activity of the hypothalamic-pituitary-adrenal axis and changes in the circadian rhythm of cortisol secretion, which can consequently further disrupt homeostasis, lead to changes in glycemic profiles, blood pressure variability, and oscillations in heart rate, increasing the risk of psychophysiological dysfunction during and after diving. Methods: We conducted two studies on a sample of 81 divers, including 14 military and 67 recreative divers. The participants completed validated questionnaires before and after diving: the Depression Anxiety Stress Scales (DASS) and the State Trait Anxiety Inventory (STAI). The first study validated the reliability and validity of newly created questionnaires (Positive and Negative Emotion Scale and Pre-diving NAT Questionnaire) and examined differences in negative thoughts, emotions, and cortisol levels between military and recreational divers. It also explored the relationship between cortisol and negative thoughts and emotions, as well as their impact on levels of cortisol, anxiety, and depression before and after diving. The second study analyzed cardiovascular stress (blood pressure, heart rate) and changes in glucose levels before and after diving in relation to psychological stress indicators among divers. Results: Negative emotions significantly influenced psychophysiological responses during diving. Meanwhile, NAT had a limited effect on physiological changes, suggesting that emotions have a stronger impact on bodily reactions than cognitive processes related to threat or failure. Professional divers maintained more stable cortisol levels compared to recreational divers, indicating better adaptation to stressful conditions. Increases in diastolic blood pressure, along with stable systolic pressure, confirmed the cardiovascular system’s resilience to changes in hydrostatic pressure, while decreases in heart rate and glucose levels after diving indicated the body’s effective physiological adaptation and reduced metabolic needs. Psychological effects include reduced stress and anxiety, as well as a decrease in negative emotions, regardless of NAT, suggesting a positive effect of diving. Furthermore, NAT did not significantly affect physiological parameters, confirming the stability of the body’s responses. The validation of the questionnaires confirmed their reliability and applicability for monitoring psychophysiological changes in divers, making them useful tools for future research and assessment of stress responses. Conclusions: Emotional regulation is key to managing psychophysiological responses during diving, with negative emotions having a stronger influence on physiological reactions than NAT. The professional divers in our study, who were generally better adapted and had more stable cortisol levels, showed greater resilience to stressful conditions compared to recreational divers, highlighting the importance of experience and training. The reductions in stress, anxiety, and negative emotions after diving indicate its therapeutic potential in improving emotional well-being, regardless of the presence of NAT. The validated questionnaires demonstrated high reliability and applicability for studying psychophysiological responses to stress in divers. The stability of physiological reactions, despite negative thoughts, emphasizes the need for further research on adaptation mechanisms and the development of strategies to reduce negative emotions and help divers adapt more easily
The importance of clinical and morphological parameters in assessing the risk of rupture and the outcome of embolization treatment of intracranial aneurysms
No full textIntrakranijske aneurizme su patološka proširenja krvnih žila, najčešće okruglog oblika koje nalazimo u oko 2% opće populacije. Patogeneza nastanka aneurizmi nije do kraja razjašnjena. Pretpostavljeni mehanizam je genetska podloga u kombinaciji sa okolišnim čimbenicima. Jedan dio aneurizmi može tijekom života rupturirati i izazvati subarahnoidalno krvarenje (SAH), relativno rijedak, ali potencijalno fatalan oblik moždanog udara. Nakon postavljene dijagnoze SAH-a (nativnim CT-om mozga i/ili lumbalnom punkcijom), unutar 24 sata potrebno je učiniti angiografski prikaz krvnih žila mozga. Glavni cilj liječenja aneurizmi je prevencija rupture (odnosno rerupture) isključivanjem aneurizme iz cirkuacije. Liječenje aneurizmi se provodi endovaskularnom embolizacijom ili neurokirurškom operacijom postavljanja metalnih klipsi na vrat aneurizme. Usprkos velikom značaju prevencije rupture, niti jedan modalitet liječenja nije bez rizika iatrogenih komplikacija, stoga je predikcija rupture intrakranijskih aneurizmi još uvijek neostvareni cilj brojnih istraživanja. Cilj našeg istraživanja bio je procijeniti rane i dugoročne kliničke i morfološke ishode endovaskularnog liječenja rupturiranih i nerupturiranih intrakranijalnih aneurizmi u kohorti bolesnika iz jednog centra. Retrospektivno smo analizirali ishode liječenja 402 endovaskularno liječene intrakranijalne aneurizme s prosječnim praćenjem od 5.5 godina. Svi uključeni pacijenti liječeni su endovaskularnim tehnikama (coill, stent ili oboje). Analizirali smo demografiju pacijenata, čimbenike rizika za rupturu aneurizme, karakteristike aneurizme te kliničke i angiografske komplikacije i ishode. Analizirali smo i usporedili podatke iz dvije skupine, rupturirane aneurizme (RA) i nerupturirane aneurizme (UA), zasebno. Od 318 uključenih bolesnika, dobar rani klinički ishod postignut je u 78.5 % RA i u 95.3 % UA. Nije bilo komplikacija u 87.71 % bolesnika s UA i u 80.45 % s RA. Periproceduralna stopa rupture za UA i RA bila je 0,8 % odnosno 2,2 %. Postotak tromboembolijskih događaja bila je 4.8 % odnosno 8% za UA i RA. Ponovno liječenje zbog rekanalizacije bilo je potrebno u 9.21 % bolesnika s UA i u 16.66 % bolesnika s RA. Rezultati našeg centra pokazali su sveukupno povoljan klinički ishod s prihvatljivim periproceduralnim komplikacijama i za RA i za UR aneurizme i dokazali su da je endovaskularna metoda sigurna i učinkovita u liječenju intrakranijalnih aneurizmi.Intracranial aneurysms are pathological dilatations of blood vessels that are usually round in shape and occur in about 2 % of the population. The pathogenesis of aneurysms is not yet fully understood. A genetic background in combination with environmental factors is suspected as the mechanism. Part of the aneurysm may rupture in the course of life and cause a subarachnoid hemorrhage (SAH), a relatively rare but potentially fatal form of stroke. Once the diagnosis of SAH has been made (via a native CT scan of the brain and/or a lumbar puncture), angiographic imaging of the blood vessels of the brain must be performed within 24 hours. The main goal of aneurysm treatment is to prevent rupture (or rerupture) by excluding the aneurysm from the circulation. Aneurysms are treated with endovascular embolization or neurosurgical procedures in which metal clips are attached to the neck of the aneurysm. Despite the great importance of preventing rupture, no treatment method is without the risk of iatrogenic complications. Therefore, the prediction of rupture of intracranial aneurysms is still an unfulfilled goal of numerous studies. The aim of our study was to evaluate the early and long-term clinical and morphologic outcomes of endovascular treatment of ruptured and unruptured intracranial aneurysms in a single-centre patient cohort. We retrospectively analysed the treatment outcomes of 402 endovascularly treated intracranial aneurysms with a mean follow-up of 5.5 years. All included patients were treated with endovascular techniques (coil, stent or both). We analysed patient demographics, risk factors for aneurysm rupture, aneurysm characteristics, and clinical and angiographic complications and outcomes. We analysed and compared the data of the two groups, ruptured aneurysms (RAs) and unruptured aneurysms (UAs), separately. Of the 318 patients included, a good early clinical outcome was achieved in 78.5 % of RAs and in 95.3 % of UAs. No complications occurred in 87.71 % of patients with UAs and in 80.45 % with RAs. The periprocedural rupture rate for UAs and RAs was 0.8 % and 2.2 %, respectively. The rate of thromboembolic events was 4.8 % and 8 % for UAs and RAs, respectively. Retreatment due to recanalization was required in 9.21 % of patients with UAs and in 16.66 % of patients with RAs. The results from our centre showed an overall favourable clinical outcome with acceptable periprocedural complications for both RA and UR aneurysms, proving that the endovascular approach is safe and effective in the treatment of intracranial aneurysms
Effect of C19H16ClN3O2S on the expression of glycosphingolipids, cytotoxicity, apoptosis, and metabolomics in the ovarian adenocarcinoma cell lines
No full textCiljevi doktorske disertacije "Učinak C19H16ClN3O2S na izražaj glikosfingolipida, citotoksičnost, apoptozu i metabolomiku u staničnim linijama adenokarcinoma jajnika" su istražiti potencijal antitumorskog spoja na staničnim linijama karcinoma jajnika SK-OV-3 i OVCAR -3 s fokusom na citotoksičnost, apoptozu, postotak matičnih stanica raka (CSC), izražaj glikosfingolipida (GSL) i metabolomiku. Proučavani spoj, 3-amino-N-(3-klor-2-metilfenil)-5-okso-5,6,7,8-tetrahidrotieno[2,3-b]kinolin-2-karboksamid (Spoj 1), sintetiziran je umjetno i upotrijebljen je za procjenu njegovih potencijalnih inhibicijskih učinaka na stanične linije raka jajnika. Citotoksičnost spoja je provedena korištenjem MTT testa koji je pokazao da je Spoj 1 bio znatno toksičan za obje stanične linije, IC50 vrijednosti od 5,5 μM za SK-OV-3 i 5,0 μM za OVCAR-3 stanične linije prilikom izloženosti Spoju 1 u trajanju od 48 sati. Nadalje, Spoj 1 dovodi do indukcije apoptoze, pri čemu je primijećeno da je statistički značajno veći udio i ranih i kasnih apoptotskih stanica u obje linije nakon tretmana. Osim toga, udio CSC (matične stanice karcinoma) se značajno smanjio nakon tretmana Spojem 1, čime se ukazuje na potencijalnu značajnu ulogu u smanjenju recidiva tumora i neuspjeha liječenja. Promjene u izražaju GSL-a zabilježene su i na CSC i na ne-CSC. U SK-OV-3 staničnoj liniji, sedam od osam promatranih GSL-a pokazalo je smanjenje CSC-a, dok su ne-CSC-i pokazali povećanje izražaja GSL-a. Stanična linija OVCAR-3 pokazala je slične trendove, iako su promjene bile manje statistički značajne. Metaboličko profiliranje provedeno uz pomoć GC-MS na staničnim linijama raka jajnika prije i nakon tretmana Spojem 1 pronašla je specifične metaboličke promjene u tretiranim stanicama u odnosu na netretirane. Metabolomika je otkrila 20 metabolita u OVCAR-3 i 21 u SK-OV-3 staničnim linijama. Stanice OVCAR-3 pokazale su značajnije promjene, s osam metabolita koji su se značajno razlikovali u tretiranim naspram netretiranih stanica, dok su samo dva metabolita pokazala značajne razlike u SK-OV-3 liniji. Rezultati pokazuju da Spoj 1 ne samo da dovodi do značajne stanične smrti, već također utječe na nekoliko ključnih signalnih puteva odgovornih za regulaciju izražaja GSL-a u staničnim linijama raka jajnika. Naglašavajući njegovu sposobnost da inducira apoptozu, smanji populaciju CSC-a i promijeni metaboličke puteve tumorskih stanica, potencijal Spoja 1 kao terapeutskog agensa protiv raka jajnika je izniman.The objectives of the doctoral dissertation "Effect of C19H16ClN3O2S on the expression of glycosphingolipids, cytotoxicity, apoptosis and metabolomics in the ovarian adenocarcinoma cell lines" are to investigate the potential of the antitumor compound on the ovarian cell lines SK-OV-3 and OVCAR-3 with a focus on cytotoxicity, apoptosis, percentage of cancer stem cells (CSC), glycosphingolipid (GSL) expression and metabolomics. The studied compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1), is artificially synthesized and we used it to evaluate its potential inhibitory effects on ovarian cancer cell lines. The cytotoxicity of the compound was performed using the MTT assay which showed that Compound 1 was significantly toxic to both cell lines, with IC50 values of 5.5 μM for SK-OV-3 and 5.0 μM for OVCAR-3 cell lines when exposed to the compound in duration of 48 hours. Furthermore, Compound 1 leads to the induction of apoptosis, with a statistically significantly higher proportion of both early and late apoptotic cells observed in both lines after treatment. In addition, CSCs show that their proportion significantly decreased after treatment with Compound 1, thus indicating the important role of Compound 1 in tumor recurrence and treatment failure. Changes in the expression of GSLs were noted in both CSCs and non-CSCs. In the SK-OV-3 cell line, seven of the eight observed GSLs showed a decrease in CSCs, while non-CSCs showed increased GSL expression. The OVCAR-3 cell line showed similar trends, although the changes were less statistically significant. Metabolic profiling performed with GC-MS on ovarian cancer cell lines before and after treatment with Compound 1 found specific metabolic changes only in treated cells. Metabolomics revealed 20 metabolites in OVCAR-3 and 21 in SK-OV-3 cell lines. OVCAR-3 cells showed more significant changes, with eight metabolites significantly different in treated versus untreated cells, while only two metabolites showed significant differences in the SK-OV-3 line. The results show that Compound 1 not only induces significant cell death, but also affects several key signaling pathways responsible for the regulation of GSL expression in ovarian cancer cell lines. Emphasizing its ability to induce apoptosis, reduce the population of CSCs, and alter the metabolic pathways of tumor cells, the potential of Compound 1 as a therapeutic agent against ovarian cancer is exceptional
The effect of wine and ethanol consumption on the survival and proliferative phase of healing after a surgically-induced myocardial infarction on the rat model
No full textUVOD: Istraživanja o kardioprotektivnim učincima vina uglavnom su usredotočena na crno vino zbog njegovog većeg sadržaja bioaktivnih spojeva u usporedbi s bijelim vinom. Iako neke studije sugeriraju postojanje kardioprotektivnog djelovanja bijelog vina, ne postoji jasan konsenzus o tome nadilaze li te koristi one koje pruža sam etanol. CILJ ISTRAŽIVANJA: Cilj ovog istraživanja bio je analizirati stope preživljenja i imunohistokemijske osobine infiltrata makrofaga te razinu aktivacije miofibroblasta u tkivu miokarda životinja koje su preživjele 96 sati nakon kirurški induciranog infarkta miokarda (IM), a koje su prethodno tijekom četiri tjedna konzumirale bijelo vino, vodenu otopinu etanola ili samu vodu. MATERIJALI I METODE: U studiji je korišteno 80 muških štakora vrste Sprague-Dawley podijeljenih u tri skupine: skupina koja je pila samo vodu, bijelo vino uz vodu ili 13% v/v vodene otopine etanola uz vodu. Nakon četverotjednog perioda konzumacije pića, IM je induciran podvezivanjem prednje interventrikularne arterije. Srca životinja koje su preživjele 96 sati nakon IM-a, te koje su konzumirale najmanje 8 mL alkoholnih pića dnevno i imale usporedive veličine IM-a, prikupljena su za imunohistokemijsku analizu. Uzorci tkiva obojeni su pan-makrofagnim biljegom (CD68) i protuupalnim biljegom makrofaga (CD163) kako bi se procijenila polarizacija makrofaga koja je ključna za cijeljenje nakon IM-a. Osim analize biljega makrofaga, provedeno je i bojanje α-SMA biljegom kako bi se ustanovila i usporedila aktivnost miofibroblasta između eksperimentalnih skupina. REZULTATI: Najviša stopa preživljenja zabilježena je u skupini koja je konzumirala bijelo vino (72,2%), dok je najniža bila u skupini koja je pila samo vodu (47,8%). Nije pronađena statistički značajna razlika u preživljenju između skupina koje su konzumirale vodenu otopinu etanola i vodu. Analiza volumena konzumiranih pića pokazala je da je niža količina konzumirane vodene otopine etanola bila povezana s većim stopama preživljenja. Suprotno tome, kod štakora koji su dnevno konzumirali oko 10 mL ili više bijelog vina nije zabilježen nijedan smrtni ishod. Imunofluorescencijskom analizom obradile su se četiri zone oko infarciranog područja —subepikardijalna, subendokardijalna i dvije periinfarktne zone. U svim analiziranim zonama najveći omjeri broja CD163 i CD68 pozitivnih makrofaga zabilježeni su u skupini koja je konzumirala bijelo vino. Što se tiče izražaja α-SMA, najmanje prosječne vrijednosti biljega dobivene su u vinskoj skupini u svim zonama, no značajnost razlike ustanovljena je samo između vinske i kontrolne skupine u periinfarktnoj zoni. ZAKLJUČAK: Zaključak studije je da umjerena konzumacija bijelog vina poboljšava preživljenje nakon IM-a, vjerojatno zahvaljujući njegovim nealkoholnim sastojcima. Konzumiranje veće količine vodene otopine etanola bilo je povezano s većom smrtnošću životinja, što ukazuje na gornju granicu zaštitnih učinaka ovog alkoholnog pića. Nijedna životinja koja je konzumirala prosječne količine vina ekvivalentne štetnoj količini etanolne otopine nije uginula, što sugerira da vino pruža dodatne zaštitne koristi koje nadmašuju učinke samog etanola. U okviru proliferativne faze cijeljenja, uočena je povećana infiltracija protupalnih naspram proupalnih makrofaga kod životinja koje su konzumirale bijelo vino u usporedbi s onima koje su pile vodenu otopinu etanola i kontrolnim životinjama. Analiza je pokazala i smanjen izražaj α-SMA biljega kod životinja koje su konzumirale bijelo vino, što je posebno naglašeno u periinfarktnoj zoni. Ovi rezultati ukazuju da bijelo vino sadrži sastojke koji dodatno podržavaju proces cijeljenja i smanjuju pretjeranu fibrozu tkiva u odnosu na druge dvije skupine. Sveukupno, istraživanja u podlozi ovog doktorskog rada pokazuju da umjerena konzumacija bijelog vina poboljšava preživljenje te potiče prikladnije cijeljenje nakon IM-a zbog mehanizama koji nadilaze učinke samog etanola, vjerojatno zahvaljujući njegovim nealkoholnim bioaktivnim spojevima.INTRODUCTION: Studies on the cardioprotective effects of wine are primarily focused on red wine due to its higher content of bioactive compounds compared to white wine. Although some studies suggest that white wine may have cardioprotective properties, there is no clear consensus on whether these benefits surpass those provided by ethanol alone. AIM OF THE STUDY: The aim of this study was to analyze the survival rates and immunohistochemical characteristics of macrophage infiltrates and the level of myofibroblast activation in myocardial tissue of animals that survived 96 hours after surgically induced myocardial infarction (MI), and that had previously consumed white wine, aqueous ethanol solution, or water alone for four weeks. MATERIALS AND METHODS: In this study, 80 male Sprague Dawley rats were divided into three groups: one group consumed only water, another consumed white wine along with water, and the third group consumed a 13% v/v ethanol/water solution along with water. After a four-week drinking period, MI was induced by ligating the left anterior descending artery. Hearts from animals that survived the 96-hour post-infarction period, consumed at least 8 mL of alcoholic beverages daily, and had comparable infarct sizes, were collected for immunohistochemical analysis. Tissue samples were stained with CD68, a pan-macrophage marker, and CD163, an anti-inflammatory macrophage marker, to assess macrophage polarization, which is crucial for healing after MI. In addition to macrophage marker analysis, α-SMA staining was performed to establish and compare myofibroblast activity between experimental groups. RESULTS: The highest survival rate was observed in the group that consumed white wine (72.2%), while the lowest was in the group that drank only water (47.8%). No statistically significant difference in survival rate was found between the groups that consumed ethanol solution and water. Analysis of the volumes of consumed beverages indicated that lower amounts of ethanol solution were associated with higher survival rates. Conversely, none of the rats that consumed around 10 mL or more of white wine daily died during the same period. Immunofluorescent analysis focused on four zones around the infarcted area: subepicardial, subendocardial, and two periinfarct zones. The highest ratios of CD163 and CD68 positive macrophages were recorded in the group consuming white wine across all analyzed zones. Regarding the α-SMA expression, the lowest average values were found in the wine group across all zones. However, statistical significance was established only between the wine and control groups in the periinfarct zone. CONCLUSION: The conclusion of the study was that moderate consumption of white wine improves survival after MI, likely due to its non-alcoholic components. Consuming a higher amount of aqueous ethanol solution is associated with higher mortality in animals, suggesting an upper limit to the protective effects of this alcoholic beverage. No animals died consuming higher amounts of white wine suggesting that wine provides additional protective benefits that exceed those of ethanol alone. Within the proliferative phase of healing, an increased infiltration of anti-inflammatory versus pro-inflammatory macrophages was observed in animals that consumed white wine compared to those that drank an aqueous ethanol solution and the control animals. The analysis also showed a reduced expression of the α-SMA marker in animals that consumed white wine, and the effect was especially pronounced in the periinfarct zone. These results indicate that white wine contains ingredients that further support the healing process and reduce excessive tissue fibrosis compared to the other two groups. Overall, the research underlying this doctoral thesis shows that moderate consumption of white wine improves survival and promotes healing after a MI through mechanisms that go beyond the effects of ethanol alone, likely due to its non-alcoholic bioactive compounds
Quality of life of cervical dystonia patients before and after botulinum toxin therapy
No full textCiljevi: Cilj istraživanja je bio prikazati kvalitetu života pacijenata, na području Splitsko-dalmatinske županije, neposredno nakon i 6 tjedana poslije primjene terapije botulinskog toksina koji se liječe u KBC-u Split te usporediti objektivnu kliničku sliku sa subjektivnom kvalitetom života 6 tjedana nakon terapije botulinskim toksinom. Materijali i metode: Provedeno istraživanje je prospektivno. Ispitanici su pacijenti s kliničkom slikom cervikalne distonije koji se liječe u dnevnoj bolnici Klinike za neurologiju u KBC Splitu u vremenskom razdoblju od prosinca 2024. do lipnja 2025. godine. Korišteni su Tsui ljestvica, ljestvica kojom se procjenjuje težina kliničke slike cervikalne distonije, i SF-36 upitnik kojim se procjenjuje kvaliteta života ispitanika u više dimenzija. U svrhu statističke obrade rezultata ispitanika primijenjene su sljedeće metode: Shapiro test, medijan, MGG test (Miao, Gel, and Gastwirth test), Studentov t-test i Wilcoxonov test rangiranja s predznakom (engl. Wilcoxon signed-rank test). Rezultati: Istraživanje je provedeno na 13 ispitanika s jasnom kliničkom slikom cervikalne distonije među kojima su svi ispitanici (100%) pripadnice ženskog spola. Medijan (mjera središnje tendencije) dobi je 67 (interkvartilnog raspona od 60 do 73 godine). Primjenom Wilcoxonovog testa rangiranja s predznakom utvrđena je P vrijednost od 0,001. Ova vrlo niska P vrijednost ukazuje na statistički značajnu razliku između rezultata Tsui ljestvice prije i nakon primjene botulinskog toksina, čime se potvrđuje da je smanjenje broja bodova nakon terapije iznimno malo vjerojatno rezultat slučajnosti. Budući da su P vrijednosti iznosile ≥ 0,05 u svim kategorijama SF-36 upitnika, može se reći da nema razlike u kvaliteti života neposredno nakon i 6 tjedana poslije primjene botulinskog toksina. Zaključci: Medijan dobi oboljelih od cervikalne distonije na području Splitsko-dalmatinske županije jest 67 (interkvartilnog raspona od 60 do 73 godine). Primjena terapije botulinskim toksinom poboljšava kliničku sliku, odnosno simptomi bolesti su manje izraženi nakon liječenja. Nema razlike u kvaliteti života prije i poslije primjene botulinskog toksina.Objectives: The aim of the study was to show the quality of life of patients living in the County of Split-Dalmatia immediately after and 6 weeks after botulinum toxin therapy who are being treated at the University Hospital of Split and to compare the objective clinical presentation with the subjective quality of life 6 weeks after botulinum toxin therapy. Materials and methods: The conducted study is prospective. The participants are patients with a clinical presentation of cervical dystonia who are being treated at the Department of Neurology, University Hospital of Split, during the period from December 2024 to June 2025. The Tsui scale, which assesses the severity of the clinical presentation of cervical dystonia, and the SF-36 questionnaire, which evaluates the patients’ quality of life across multiple dimensions, were used in the assessment. For the purpose of statistical analysis of the results, the following methods were applied: the Shapiro-Wilk test, median, MGG test (Miao, Gel, and Gastwirth test), Student's t-test, and the Wilcoxon signed-rank test. Results: The study was conducted on 13 participants with a clear clinical presentation of cervical dystonia, all of whom (100%) were female. The median age (as a measure of central tendency) was 67 years, with an interquartile range from 60 to 73 years. Using the Wilcoxon signed-rank test, a P-value of 0.001 was obtained. This very low P-value indicates a statistically significant difference between the Tsui scale scores before and after the administration of botulinum toxin therapy, confirming that the observed reduction in scores is highly unlikely to be due to chance. Since the P-values were ≥ 0.05 in all categories of the SF-36 questionnaire, it can be concluded that there was no significant difference in quality of life immediately after and six weeks after the application of botulinum toxin. Conclusions: The median age of patients with cervical dystonia in the County of Split-Dalmatia is 67 years (with an interquartile range of 60 to 73 years). The administration of botulinum toxin therapy improves the clinical picture, meaning that the symptoms of the disease are less pronounced after treatment. There is no significant difference in quality of life before and after the administration of botulinum toxin therapy
Povezanost niskih normalnih razina TSH-a i rizika od kontrastom inducirane hipertireoze u pacijenata s autonomnim adenomom štitnjače: retrospektivna studija
No full textObjectives: The primary objective of this retrospective case–control study was to determine whether lower pre-contrast TSH levels are associated with an increased risk of ICM-induced hyperthyroidism in euthyroid patients with autonomous thyroid adenoma. Secondary aims included identifying a specific low-normal TSH cutoff for risk stratification and evaluating other potential risk factors, such as age, iodine dose, renal or hepatic impairment, and imaging modality in the development of contrast-induced hyperthyroidism. Methods: Medical records of 100 patients at Sana Hospital Coburg (January 2014- December 2022) who underwent ICM-enhanced procedures were reviewed. Fifty AA cases (euthyroid before ICM, developed hyperthyroidism afterward) and fifty matched controls (euthyroid before and after ICM, no AA) were included. Exclusion criteria comprised prior thyroid hormone or antithyroid therapy, Graves’ disease, and missing thyroid labs. Collected data encompassed pre- and post- ICM TSH, free T3/ T4, administered iodine dose, age, sex, renal function, hepatic function (elevated AST/ALT), procedure type (contrast-enhanced CT or coronary angiography), and thyroid imaging (when available). Laboratory assays used the cobas™ 6000 analyzer. Continuous variables were compared via Mann–Whitney U test; categorical variables by Chi-square or Fisher’s exact test. ROC analysis determined the optimal TSH cutoff, calculating sensitivity, specificity, and odds ratio (OR) with P < 0.05 considered significant. Results: Cases were older than controls (78.9 ± 7.3 vs. 72.5 ± 10.2 years; p < 0.001). Mean pre-ICM TSH was significantly lower in cases (0.87 ± 0.73 μU/mL) vs. controls (1.53 ± 1.00 μU/mL; p < 0.001). ROC analysis identified TSH < 0.69 μU/mL as the optimal threshold (AUC = 0.75; 60 % sensitivity; 82 % specificity), with an OR of 6.68 (95 % CI 2.61–17.10; p < 0.001). Iodine dose (35.6 ± 12.8 g vs. 32.9 ± 10.8 g; p = 0.074), renal impairment (80 % vs. 84 %; p = 0.795), and hepatic impairment (14 % vs. 12 %; p = 1.000) did not differ significantly between groups. Coronary angiography occurred more frequently in cases (54 % vs. 30 %; p = 0.025), while contrast-enhanced CT was more common in controls (70 % vs. 46 %; p = 0.025), likely reflecting chance. Thyroid imaging confirmation of AA was available for only a subset of cases. Conclusion: A pre-contrast TSH cutoff of < 0.69 μU/mL still within the normal reference range indicates a markedly higher risk of ICM-induced hyperthyroidism in AA patients. Intrinsic thyroid autonomy, rather than iodine dose or organ function, is the principal risk factor, with older age further increasing susceptibility. Clinically, because TSH is routinely measured prior to ICM, low-normal values (especially < 0.7 μU/mL) in patients with known or suspected AA should trigger closer monitoring or prophylaxis (e.g., short-course methimazole). Study limitations include the retrospective single-center design, lack of uniform thyroid scintigraphy, unmeasured confounders (dietary iodine intake, detailed ultrasound morphology), and limited applicability to iodine-deficient or non-Caucasian populations. Future research should prospectively validate this TSH cutoff across diverse iodine-status regions, incorporate standardized scintigraphy to confirm nodule autonomy, explore adjunctive biomarkers for improved risk stratification, and conduct randomized trials comparing prophylactic regimens to develop evidence-based guidelines for preventing ICM-provoked thyrotoxicosis.Ciljevi: Primarni cilj ove retrospektivne studije bio je ispitati povezanost nižih prekontrastnih razina tireostimulirajućeg hormona (TSH) unutar referentnog raspona (0,4–4,0 μU/mL) s rizikom od razvoja hipertireoze nakon primjene jodnog kontrastnog sredstva (ICM) u eutiroidnih pacijenata s autonomnim adenomom štitnjače (AA). Sekundarni su ciljevi bili odrediti prag (cut-off) niskog normalnog TSH-a za stratifikaciju rizika te ispitati utjecaj dobi, ukupne doze joda, bubrežne i jetrene funkcije te vrste postupka (CT ili koronarografija) na učestalost kontrastom inducirane hipertireoze. Materijali i metode: U analizu su ušli podaci 100 pacijenata iz Sana bolnice u Coburgu koji su između siječnja 2014. i prosinca 2022. bili podvrgnuti postupcima s primjenom jodnog kontrastnog sredstva (ICM). Skupinu slučajeva (n = 50) činili su eutiroidni pacijenti s dijagnosticiranom AA koji su unutar četiri tjedna nakon ICM-a razvili biokemijsku ili kliničku hipertireozu. Kontrolnu skupinu (n = 50) činili su eutiroidni pacijenti bez AA koji su ostali eutiroidni nakon ICM-a. Iz obje skupine isključeni su pacijenti na terapiji hormonima štitnjače ili antitireoidnim lijekovima, bolesnici s Gravesovom bolešću te oni s nepotpunim laboratorijskim podacima. Prikupljeni su podaci o pre- i post-ICM vrijednostima TSH-a, slobodnog T3 i slobodnog T4, ukupnoj dozi joda (u gramima), dobi, spolu, bubrežnoj funkciji (eGFR < 50 mL/min/1,73 m²), jetrenoj funkciji (povišeni AST/ALT), vrsti postupka (kontrastni CT ili koronarografija) te, ako su bili dostupni, nalazima ultrazvuka ili scintigrafije štitnjače za potvrdu AA. Krvni su uzorci analizirani cobas™ 6000 analizatorom metodom elektrohemiluminescentnog imunotesta. Kontinuirane varijable uspoređivane su Mann–Whitney U testom, a kategorijske χ² ili Fisherovim testom. ROC analiza korištena je za određivanje optimalnog praga TSH-a, uz izračun osjetljivosti, specifičnosti i omjera vjerojatnosti (OR). Statistička je značajnost definirana kao P < 0,05. Rezultati: Pacijenti u skupini slučajeva bili su stariji od onih u kontrolnoj skupini (78,9 ± 7,3 vs. 72,5 ± 10,2 godina; p < 0,001). Srednja prekontrastna vrijednost TSH-a bila je značajno niža kod slučajeva (0,87 ± 0,73 μU/mL) nego kod kontrola (1,53 ± 1,00 μU/mL; p < 0,001). ROC analiza identificirala je prag TSH-a < 0,69 μU/mL, koji je pokazao AUC = 0,75, osjetljivost 60 % i specifičnost 82 %, uz OR = 6,68 (95 % CI 2,61–17,10; p < 0,001). Ukupna doza joda (35,6 ± 12,8 g vs. 32,9 ± 10,8 g; p = 0,074) te bubrežna (eGFR < 50: 80 % vs. 84 %; p = 0,795) i jetrena funkcija (povišeni AST/ALT: 14 % vs. 12 %; p = 1,000) nisu se značajno razlikovale između skupina. Koronarografijom s ICM-om igralo je 54 % pacijenata u skupini slučajeva, nasuprot 30 % u kontrolnoj skupini (p = 0,025), dok je kontrastni CT češći u kontrolama (70 % vs. 46 %; p = 0,025); no zbog male veličine podskupina ovaj je nalaz vjerojatno slučajan. Potvrda AA ultrazvukom ili scintigrafijom bila je dostupna samo za dio slučajeva. Zaključci: Prekontrastna vrijednost TSH-a ispod 0,69 μU/mL—iako još unutar referentnog raspona— znači šest puta veći rizik od razvoja hipertireoze inducirane ICM-om kod pacijenata s AA. Intrinzična autonomija štitnjače, a ne sama količina joda ili bubrežna/jetrena funkcija, glavni je čimbenik rizika, a starija dob dodatno povećava ranjivost. Budući da se TSH rutinski mjeri prije primjene ICM-a, niske normalne vrijednosti (< 0,7 μU/mL) kod pacijenata sa znanom ili sumnjivom AA trebaju potaknuti pojačano praćenje ili preventivnu terapiju (npr. kratkotrajna terapijametimazolom).Ograničenja studije uključuju retrospektivni jednocentrični dizajn, nedostatak uniformne scintigrafije štitnjače za sve sudionike, neprikupljene podatke o dnevnom unosu joda i detaljnu ultrazvučnu morfologiju nodula te ograničenu primjenjivost na populacije iz regija s deficitom joda ili druge etničke skupine. Preporučuje se da buduća istraživanja prospektivno potvrde prag od 0,69 μU/mL u različitim regijama glede stanja joda, uključe standardiziranu scintigrafiju štitnjače za procjenu autonomne funkcije nodula, istraže dodatne biomarkere za stratifikaciju rizika te provedu randomizirane studije uspoređujući protokole preventivne terapije kako bi se izradile precizne i dokazane smjernice za sprječavanje ICM-provocirane hipertireoze