Veterinary medicine - Repository of PHD, master's thesis
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Administration of disease-modifying drugs and vaccination for individuals with multiple sclerosis
No full textMultipla skleroza (MS) je kronična, autoimuna bolest središnjeg živčanog sustava koju karakteriziraju upala, demijelinizacija i neurodegeneracija. S obzirom na širok spektar simptoma, uključujući motoričke, senzorne, vizualne i kognitivne poremećaje, MS značajno utječe na kvalitetu života oboljelih. Iako etiologija MS-a još uvijek nije u potpunosti razjašnjena, poznato je da ključnu ulogu imaju genetski, imunološki i okolišni čimbenici. MS je bolest s velikim varijacijama u prezentaciji i progresiji, često opisana kao "bolest s tisuću lica." Terapijski pristupi u MS-u fokusiraju se na modifikaciju tijeka bolesti, smanjenje učestalosti relapsa, progresiju onesposobljenosti i ublažavanje simptoma. Uz već poznate terapije, istražuju se i novi lijekovi koji ciljaju specifične patološke mehanizme MS-a. Cijepljenje protiv različitih infekcija od ključne je važnosti za osobe s MS-om, s obzirom na njihovu povećanu ranjivost prema infekcijama. Međutim, sigurnost i učinkovitost cijepljenja kod ove populacije još uvijek su predmet istraživanja. Postojeće smjernice preporučuju cijepljenje protiv gripe, pneumokoka i drugih preventabilnih bolesti, no potrebna su daljnja istraživanja kako bi se bolje razumjeli učinci cijepljenja na tijek MS-a i imunološki odgovor bolesnika. Unatoč značajnom napretku u razumijevanju i liječenju multiple skleroze, bolest ostaje izazov za bolesnike i liječnike. Razumijevanje složenih imunoloških mehanizama i utjecaja genetskih i okolišnih čimbenika ključno je za razvoj novih terapija. Osim toga, cijepljenje predstavlja važan aspekt preventivne skrbi za osobe s MS-om, naglašavajući potrebu za daljnjim istraživanjima kako bi se osigurala njihova sigurnost i učinkovitost. Ovaj rad pruža sveobuhvatan pregled trenutnog stanja znanja o MS-u, uključujući etiologiju, dijagnostiku, liječenje i potencijalne smjerove za buduća istraživanja.Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. Given the wide spectrum of symptoms, including motor, sensory, visual, and cognitive disorders, MS significantly impacts the quality of life of affected individuals. Although the etiology of MS is not yet fully understood, it is known that genetic, immunological, and environmental factors play crucial roles. MS is a disease with great variability in presentation and progression, often described as the "disease with a thousand faces." Therapeutic approaches in MS focus on modifying the disease course, reducing the frequency of relapses, disability progression and alleviating symptoms. In addition to traditional therapies, new drugs targeting specific pathological mechanisms of MS are being investigated. Vaccination against various infections is crucial for patients with MS, given their increased vulnerability to infections. However, the safety and efficacy of vaccination in this population remain subjects of research. Current guidelines recommend vaccination against influenza, pneumococcus, and other preventable diseases, but further research is needed to better understand the effects of vaccination on the course of MS and the immune response of patients. Despite significant progress in understanding and treating multiple sclerosis, the disease remains a challenge for patients and clinicians. Understanding the complex immunological mechanisms and the impact of genetic and environmental factors is key to developing new therapies. Additionally, vaccination represents an important aspect of preventive care for MS patients, highlighting the need for further research to ensure their safety and efficacy. This paper provides a comprehensive overview of the current state of knowledge about MS, including its etiology, diagnosis, treatment, and potential directions for future researc
Methods of endometrial preparation for transfer of cryopreserved embryos
No full textKrioembriotransfer (FET) je danas sve češća metoda medicinski pomognute oplodnje kojom se prethodno kriopohranjen zametak prenosi u maternicu s ciljem liječenja neplodnosti. Za svaki prijenos zamrznutog zametka i postizanje njegove implantacije potrebno je pripremiti endometrij. Uspješnost same metode najviše ovisi o receptivnosti endometrija te o usklađenosti receptivnosti endometrija s fazom razvoja u kojoj je zametak krioprezerviran. Danas postoji nekoliko metoda pripreme endometrija: prirodni ciklus, modificirani prirodni ciklus s hCG primjenom, HRT (umjetni) ciklus te stimulirani ciklus. Prirodni i modificirani prirodni ciklus se provode kod žena s redovitim menstrualnim ciklusom te se transfer zametka odvija u skladu s njim. HRT ciklus koristi egzogenu suplementaciju hormona estrogena i progesterona čime simulira fiziološki ciklus. Za razliku od prirodnog i stimuliranog ciklusa, nedostatak ove metode je izostanak formiranja žutog tijela potrebnog za prilagodbu na kardiovaskularne promjene tijekom rane trudnoće. Zbog navedenog je uočena povećana učestalost hipertenzivnih poremećaja i komplikacija u trudnoći poput preeklampsije i makrosomije. Stimulirani ciklus je metoda izbora kod anovulatornih žena te se za indukciju ovulacije najčešće koriste klomifen citrat, letrozol ili niske doze FSH. Prema dosadašnjim studijama nije dokazana veća učinkovitost određene metode u odnosu na druge po pitanju uspješnosti implantacije zametka i ishoda trudnoće. Ipak, individualizirani pristup u pripremi endometrija omogućava prilagodbu terapije specifičnim potrebama svake pacijentice, uzimajući u obzir njezine jedinstvene karakteristike i čimbenike rizika. Time se povećavaju šanse za uspješan ishod trudnoće, no važno je provesti dodatna istraživanja kako bi se identificirali najbolji protokoli i strategije u ovom procesu.Frozen embryo transfer (FET) is an increasingly common method of medically assisted reproduction in which a previously cryopreserved embryo is transferred to the uterus to treat infertility. Preparing the endometrium is necessary for each frozen embryo transfer and achieving its implantation. The success of this method largely depends on the receptivity of the endometrium and the synchronization of the endometrial receptivity with the developmental stage at which the embryo was cryopreserved. Today, there are several methods for preparing the endometrium: the natural cycle, the modified natural cycle with hCG administration, the HRT (artificial) cycle and the stimulated cycle. The natural and modified natural cycles are carried out in women with regular menstrual cycles, with the embryo transfer taking place in alignment with their cycles. The HRT cycle uses exogenous hormone supplementation of estrogen and progesterone to simulate a physiological cycle. Unlike the natural and stimulated cycles, a disadvantage of this method is the absence of corpus luteum formation, which is necessary for adaptation to cardiovascular changes during early pregnancy. As a result, an increased incidence of hypertensive disorders and pregnancy complications such as preeclampsia and macrosomia has been observed. The stimulated cycle is the method of choice for anovulatory women, and ovulation is most often induced using clomiphene citrate, letrozole, or low doses of FSH. According to current studies, no particular method has proven to be more effective than others regarding embryo implantation success and pregnancy outcomes. However, an individualized approach to endometrial preparation allows for therapy to be personalized to the specific needs of each patient, considering their unique characteristics and risk factors. This increases the chances of a successful pregnancy outcome, still additional research is essential to identify the best protocols and strategies in this process
Treatment for epidermal growth factor receptor mutation positive lung cancer
No full textRak pluća predstavlja ozbiljan globalni zdravstveni problem s obzirom da je vodeći uzrok smrti od raka diljem svijeta. Rano otkrivanje raka pluća je ključ za poboljšanje prognoze bolesnika. Nažalost, rano postavljanje dijagnoze često je izazovno, s obzirom na nespecifične simptome koje bolesnici mogu imati u početnoj fazi bolesti. Većina bolesnika stoga bude dijagnosticirana u uznapredovalom stadiju što znatno smanjuje izglede za izlječenje. No, zahvaljujući napretku u molekularnom profiliranju raka, otvara se mogućnost personaliziranog pristupa liječenju. Identificirane su ključne mutacije, poput onih na receptorima epidermalnog faktora rasta (EGFR), koje igraju važnu ulogu u razvoju raka pluća nemalih stanica (NSCLC). Otkriće inhibitora EGFR tirozin kinaze (TKI) predstavlja prekretnicu u liječenju NSCLC, budući da ova ciljana terapija poboljšava kvalitetu života bolesnika, smanjuje nuspojave i produljuje vrijeme preživljenja bez progresije bolesti. Iako su donijeli revoluciju u liječenju NSCLC, nije rijetko da bolesnici steknu rezistenciju na EGFR-TKI. Međutim, nova istraživanja i nove tehnologije otvaraju put ka razumijevanju mehanizama nastanka rezistencije i razvoju novih terapijskih strategija i daju nadu da će se u budućnosti poboljšati ishodi za sve bolesnike koji se bore s ovom teškom bolešću.Lung cancer is a serious global health problem as it is the leading cause of cancer death worldwide. Early detection of lung cancer is key to improving patient prognosis. Unfortunately, early diagnosis is often challenging due to the non-specific symptoms that patients may experience in the early stages of the disease. Most patients are therefore diagnosed at an advanced stage, which significantly reduces the chances of a cure. However, thanks to advances in molecular profiling of cancer, the possibility of a personalized approach to treatment is opening up. Key mutations have been identified, such as those on epidermal growth factor receptors (EGFR), which play an important role in the development of non-small cell lung cancer (NSCLC). The discovery of EGFR tyrosine kinase inhibitors (TKIs) has been a breakthrough in the treatment of NSCLC, as this targeted therapy improves patients' quality of life, reduces side effects and prolongs progression-free survival. While they have revolutionized the treatment of NSCLC, it is not uncommon for patients to develop resistance to EGFR-TKIs. However, new research and new technologies are opening up the way to understanding the mechanisms of resistance and developing new therapeutic strategies, offering hope that future outcomes for all patients battling this difficult disease will be improved
Ethical attitudes and perspectives of AI use in medicine between Croatian and Slovenian faculty members of school of medicine: Cross-sectional study
No full textBackground: Artificial intelligence (AI) is present in preclinical, clinical and research work, in various branches of medicine. Researchers and teachers at school of medicines may have different ethical attitudes and perspectives about the implementation of AI systems in medicine.
Methods: We conducted an online survey among researchers and teachers (RTs) at the departments and institutes of two Slovenian and four Croatian Schools of Medicine.
Results: The sample included 165 and 214 researchers and teachers in Slovenia and Croatia, respectively. The sample of respondents in Slovenia and Croatia was comparable in demographical characteristics. All participants reported high emphasis on the bioethical principles when using artificial intelligence in medicine, its usefulness in certain circumstances, but also caution regarding companies providing AI systems and tools. Slovenian and Croatian researchers and teachers shared three similar perspectives on the use of AI in medicine-complying with highest ethical principles, explainability and transparency and usefulness of AI tools. Higher caution towards use of AI in medicine and effect on autonomy of physicians was expressed in Croatia, while in Slovenia high emphasis was put on understanding how AI works, but also the concerns regarding willingness and time of physicians to learn about AI.
Conclusion: Slovenian and Croatian researchers and teachers share ethical attitudes and perspectives with international researchers and physicians. It is important to facilitate understanding of the implications of AI use in medicine and set a solid evidence-based ground to tackle ethical and legal issues
Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies
No full textBackground and objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods.
Methods: We performed a retrospective cohort study using data from the MSBase Registry including pregnancies conceived after December 31, 2010, from women aged 18 years and older, with relapsing-remitting MS or clinically isolated syndrome. Women were classified by preconception exposure to DMTs, including OCR, rituximab (RTX), natalizumab (NAT), stratified into active (NAT-A; continued ≥28 weeks of gestation, restarted ≤1 month postpartum) or conservative (NAT-C; continued ≤4 weeks of gestation, restarted >1 month postpartum) strategies, dimethyl fumarate (DMF) or low-efficacy DMTs (interferon-beta, glatiramer acetate). Annualized relapse rates (ARRs) were calculated for 12-month prepregnancy, pregnancy, and 6-month postpartum periods.
Results: A total of 2,009 live births from 1,744 women were analyzed, including 73 live births from 69 women treated with preconception OCR. For OCR, no within-pregnancy relapse was observed and 3 women (4.1%) experienced 1 relapse in the postpartum period (ARR 0.09 [95% CI 0.02-0.27]). For NAT-A, 3 (3.7%) of 82 women relapsed during pregnancy (0.05 [0.01-0.15]) and 4 (4.9%) relapsed during postpartum (0.10 [0.03-0.26]). However, for NAT-C, 13 (15.9%) of 82 women relapsed within pregnancy (0.32 [0.20-0.51]) and 25 (30.5%) relapsed during postpartum (0.74 [0.50-1.06]). In the low-efficacy DMT group, 101 (7.6%) of 1,329 women experienced within-pregnancy relapse (0.12 [0.10-0.14]), followed by an increase in postpartum relapse activity with 234 women (17.6%) relapsing (0.43 [0.38-0.48]). This was similarly seen in the DMF group with 13 (7.9%) of 164 women experiencing within-pregnancy relapse (0.12 [0.06-0.20]) and 25 (15.2%) of 164 relapsing postpartum (0.39 [0.26-0.57]). Our RTX cohort had 0 of 24 women experiencing within-pregnancy relapse and 3 (12.5%) of 24 experiencing postpartum relapse.
Discussion: Women treated with OCR or NAT-A were observed to have low relapse rates during pregnancy and postpartum. NAT-C was associated with increased risk of relapses. There was no within-pregnancy relapse in our RTX cohort, although we caution overinterpretation due to our sample size. An effective DMT strategy with a favorable safety profile for the mother and infant should be discussed and implemented well in advance of planning a family.
Classification of evidence: This study provides Class III evidence that for women with relapsing-remitting MS or clinically isolated syndrome who become pregnant, ocrelizumab, rituximab, and natalizumab (continued ≥28 weeks of gestation and restarted ≤1 month postpartum) were associated with reduced risk of relapses, compared with other therapeutic strategies
Association of adenoid hypertrophy and clinical parameters with preoperative polygraphy in pediatric patients undergoing adenoidectomy
No full textBackground: Adenotonsillar hypertrophy is the most frequent cause for obstructive sleep apnea (OSAS) in children. In patients with small tonsils and where adenoid size cannot be assessed, the indication for adenoidectomy often relies on clinical symptoms. However, data on the association of clinical parameters and adenoid hypertrophy with OSAS severity in children undergoing an adenoidectomy is sparse.
Aim: To investigate the correlation of patient characteristics, adenoid hypertrophy, and clinical symptoms with OSAS severity in pediatric patients indicated for an adenoidectomy.
Methods: We performed a retrospective chart review of all pediatric patients at our tertiary referral center between 2018 and 2023 who underwent polygraphy (PG) for OSAS diagnostics. Adenoid hypertrophy was assessed as adenoid-choanal ratio (AC-ratio) via nasal endoscopy and clinical symptom score (CS) via physical examination and parental survey. We included all symptomatic children with mild to severe OSAS (apnea-hypopnea index (AHI) ≥ 1). Exclusion criteria were obesity according to BMI and/or the presence of systemic diseases. The patients were divided according to age in a preschool and school cohort. Patient characteristics and PG data were compared between both groups. Linear regression analysis was used to investigate the association of AC-ratio, CS and BMI with the AHI.
Results: A total of 121 patients were identified of which 81 were included in our study, resulting in 42 and 39 patients from 3-5 and 6-14 years of age, respectively. We observed a significant correlation between CS and BMI (p = 0.026) and the CS and AC-ratio (p < 0.001). Univariable regression analysis showed significant association of the AC-ratio and CS with AHI-score for the total (p < 0.001), the preschool (p < 0.001), and the school cohort (p < 0.001). In multivariable regression analysis, the significant association of AC-ratio and CS remained in the total (p = 0.014; p < 0.001), and the preschool cohort (p = 0.029; p = 0.002). However, only the CS remained as positive predictor in the school cohort.
Conclusion: AC-ratio and clinical symptoms seem to be reliable predictors for OSAS severity in patients between 3-14 years of age. Moreover, only clinical symptoms were associated with OSAS severity in schoolchildren. Future investigation should contribute to the validation of our results
Effects of Sodium–Glucose Co-Transporter 2 Inhibitors on Serum Chloride Concentrations in Patients with Heart Failure
No full textBackground and aims: In the past few years, some reports have shown that serum chloride concentration is a more powerful prognostic predictor than serum sodium levels in heart failure (HF). Elevated Na/Cl ratio has shown to be independently associated with all-cause death in acute HF. We evaluated changes in serum chloride concentrations and Na/Cl ratio in correlation with various clinical factors during 12 months of follow-up in patients in whom SGLT2is were initiated as part of HF therapy.
Patients and methods: This was a prospective observational study conducted at University Hospital Dubrava and involving patients with HF. We included 241 participants between May 2021 and April 2023. All data were obtained before the introduction of SGLT2is, and the same parameters were obtained at 6 and 12 months of follow-up as well.
Results: The results show that higher chloride concentration at both 6 and 12 months is an independent predictor of lower NT-proBNP levels. The chloride concentrations did not differ significantly between these groups in the follow-up period. There were no statistically significant differences in the Na/Cl ratio at different timepoints. The presence of cardiovascular risk factors did not significantly affect the increase in chloride concentration.
Conclusions: Our results suggest that hypochloremia could be a potentially modifiable risk factor, given the influence of SGLT2is on chloride concentration, but also an ominous sign of a poor outcome in patients with HF. We believe that the determination of chloride concentrations should become routine in the monitoring of patients with HF
Implantable Cardioverter Defibrillators in Prevention of Sudden Cardiac Death in Kidney Transplant Recipients: A Case Series and an Appraisal of Current Evidence
No full textBackground: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of mortality among kidney transplant recipients (KTRs). While implantable cardioverter defibrillators (ICDs) are established for SCD prevention in the general population, data on the benefits in patients with CKD is scarce and controversial, and there is no established general consensus on their use in this group of patients. Furthermore, data for KTRs are lacking. The aim of this study is to present our experience with ICDs in KTRs and evaluate the outcomes in this population.
Methods: We retrospectively analyzed medical records of KTRs who received a kidney allograft between October 1973 and December 2023 and received ICDs for the prevention of SCD.
Results: Of 2282 KTRs, 10 patients (0.44%) underwent an ICD implantation with an average age of 60.6 years at the time of implantation; 9 were male. Primary prevention of SCD was the most common indication, with only one patient receiving an ICD following sudden cardiac arrest. The female patient received an ICD while on dialysis, and the rest of the patients received ICDs in the posttransplant period with an average time of 9.1 years after KT. Kidney allograft function was reduced in all patients at the time of the ICD implantation with an average estimated glomerular filtration rate (eGFR) of 44 mL/min/1.73 m2. No ICD-related complications were recorded. Six patients are alive with an average follow-up of 5.2 years.
Conclusions: ICD implantation in carefully selected KTRs may offer survival benefits and can be a valuable tool in preventing SCD. Larger studies are needed to confirm these findings and establish clear guidelines for ICD use in this specific population
The effect of light therapy on plasma levels of brain-derived neurotrophic factor and serum levels of interleukin-6 in patients with treatment-resistant depression
No full textDepresivni poremećaj je među vodećim poremećajima koji uzrokuju pad kvalitete života, radne i socijalne funkcionalnosti, a oko 30 % oboljelih ima terapijski rezistentni depresivni poremećaj (TRDP). Terapija svjetlom se kao dodatna metoda primjenjuje u liječenju TRDP-a. Do sada nisu ispitivani moždani neurotrofni čimbenik (BDNF) i interleukin-6 (IL-6) kao periferni pokazatelji djelovanja fototerapije. Rezultati istraživanja u koje je bilo uključeno 60 ženskih ispitanika ukazuju da nakon 4 tjedna fototerapije nema značajne promjene u koncentracijama BDNF-a u plazmi i IL-6 u serumu, kao i da poboljšanje depresivnih simptoma nije u korelaciji s promjenama koncentracija BDNF-a i IL-6. Ispitanice koje su prema ocjenskim ljestvicama HAMD-17 i MADRS dobro odgovorile na fototerapiju ili su postigle remisiju, imale su veći porast perifernih koncentracija BDNF-a i IL-6, u odnosu na one koje nisu dobro odgovorile. Istraživanje je pridonijelo boljem razumijevanju djelovanja fototerapije i njene primjene kod TRDP-a, što otvara dodatne mogućnosti za buduće studije.Depressive disorder is among the leading disorders that cause a decline in quality of life, work and social functionality, and about 30 % of patients have treatment-resistant depression (TRD). Light therapy is used as an additional method in the treatment of TRD. So far, brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) have not been investigated as peripheral indicators of the effect of phototherapy. The results of the research involving 60 female subjects indicate that there is no significant change in plasma levels of BDNF and serum levels of IL-6 after 4 weeks of phototherapy, as well as that the improvement of depressive symptoms is not correlated with the changes in levels of BDNF and IL-6. Subjects who, according to the HAMD-17 and MADRS rating scales, responded well to phototherapy or achieved remission, had a greater increase in peripheral levels of BDNF and IL-6 compared to those who did not respond well. The research contributed to a better understanding of the effect of phototherapy and its application in TRD, which opens additional opportunities for future studies
Prikaz bolesnika s korozivnom ozljedom gornjeg probavnog sustava
No full textOzljede nastale ingestijom kiseline javljaju se incidencijom 6/1000 pacijenta te su povezane s izrazito kompleksnim morbiditetom i mortalitetom. U ovom radu prikazana je ozljeda nastala ingestijom sumporne kiseline. Po ingestiji javljaju se korozivne ozlijede gornjeg probavnog sustava, te postoji velika mogućnost perforacije želuca sa peritonitisom. Gradacija ozljede klasificira se po endoskopskoj obradi. Klinička slika ovisi o težini ozljede, a manifestira se stridorom, disfagijom, krvarenjem, peritonitisom i medijastinitisom. Inicijalno zbrinjavanje obuhvaća zbrinjavanje prohodnosti dišnog puta pri čemu se vrlo često javlja otežana intubacija, potreba za mehaničkom ventilacijom i ispravljanje metaboličke acidoze. Prikazane su daljnje opcije liječenja, suportivne mjere, te opcije kirurškog i ne kirurškog liječenja, rane i kasne komplikacije kao što su stenoza jednjaka, njihovo zbrinjavanje i prevencija, te preporuka primjene omeprazola i glukokortikoida. Prikazan je slučaj 44-godišnjeg muškarca po ingestiji sumporne kiseline, incijalna procjena korozivne ozlijede, i njeno zbrinjavanje u jedinici intenzivnog liječenja, dinamika liječenja i evaluacija kasnih komplikacija