Veterinary medicine - Repository of PHD, master's thesis
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Molekularni mehanizmi imunološkog odgovora i aktivacije inflamasoma u Parkinsonovoj bolesti: plan upravljanja istraživačkim podacima
No full textSGLT2 Inhibitors and Their Effect on Urolithiasis: Current Evidence and Future Directions
No full textUrolithiasis (UL) is increasingly prevalent due to rising cardiorenometabolic diseases, posing significant management challenges despite advances in urological techniques. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used for type 2 diabetes mellitus, chronic kidney disease, and heart failure, have emerged as a potential novel approach for UL treatment. These inhibitors may help reduce the risk of urolithiasis, particularly in patients with diabetes, by improving glycemic control and altering urinary chemistry, which are crucial factors in stone formation. However, the changes in urinary composition induced by SGLT2 inhibitors might also increase the risk of uric acid stone formation. This review evaluates the potential of SGLT2 inhibitors in managing UL, highlighting both the benefits and the risks. While these inhibitors show promise in reducing new and recurrent urinary stones in patients with diabetes, data on their effects in patients without diabetes who form stones are limited. Current human evidence largely comes from post hoc analyses of randomized controlled trials (RCTs) and large-scale database studies, with only one study providing detailed stone composition data. Experimental studies in animal models and cell lines have focused on calcium oxalate (CaOx) stones, showing that SGLT2 inhibitors specifically target CaOx stone formation and related renal inflammation. Although primarily studied for CaOx stones, their potential impact on other calcium-containing stones, such as calcium phosphate, remains promising. Further research is needed to explore their therapeutic potential and optimize treatment strategies
Dihydrolipoamide dehydrogenase deficiency in five siblings with variable phenotypes, including fulminant fatal liver failure despite good engraftment of transplanted liver
No full textDihydrolipoamide dehydrogenase (DLD) deficiency can, in one of its forms, be a rare cause of acute liver failure. Clinical presentation is nonspecific. Biochemical findings can reflect metabolic block, but vary depending on patient and his condition. Consensus treatment guidelines do not exist. We present a family with five members suffering from DLD deficiency. Patient 1 presented with emesis, mental deterioration, and fulminant hepatic failure, which required high‐urgency liver transplantation. His younger brother, patient 2, experienced unexplained hypoglycemia and metabolic acidosis on the second day after cardiac surgery. Three affected younger siblings were asymptomatic. In patients with acute liver failure of unknown etiology urgent metabolic work‐up should be done, and whole exome sequencing considered. Liver transplantation remains life‐saving treatment option, but its outcome may be dependent on etiology‐specific supportive treatment
Implementing verifiable oncological imaging by quality assurance and optimization (i‑Violin)
No full textBackground: Advanced imaging techniques play a pivotal role in oncology. A large variety of computed tomography (CT) scanners, scan protocols, and acquisition techniques have led to a wide range in image quality and radiation exposure. This study aims at implementing verifiable oncological imaging by quality assurance and optimization (i-Violin) through harmonizing image quality and radiation dose across Europe.
Methods: The 2‑year multicenter implementation study outlined here will focus on CT imaging of lung, stomach, and colorectal cancer and include imaging for four radiological indications: diagnosis, radiation therapy planning, staging, and follow-up. Therefore, 480 anonymized CT data sets of patients will be collected by the associated university hospitals and uploaded to a repository. Radiologists will determine key abdominopelvic structures for image quality assessment by consensus and subsequently adapt a previously developed lung CT tool for the objective evaluation of image quality. The quality metrics will be evaluated for their correlation with perceived image quality and the standardized optimization strategy will be disseminated across Europe.
Results: The results of the outlined study will be used to obtain European reference data, to build teaching programs for the developed tools, and to create a culture of optimization in oncological CT imaging.
Conclusion: The study protocol and rationale for i‑Violin, a European approach for standardization and harmonization of image quality and optimization of CT procedures in oncological imaging, is presented. Future results will be disseminated across all EU member states, and i‑Violin is thus expected to have a sustained impact on CT imaging for cancer patients across Europe
Comparison of Autologous and Allogeneic Adipose-Derived Stem Cells in Kidney Transplantation: Immunological Considerations and Therapeutic Efficacy
No full textRegenerative medicine shows significant potential in treating kidney diseases through the application of various types of stem and progenitor cells, including mesenchymal stem cells (MSCs), renal stem/progenitor cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Stem cells possess the unique ability to repair injured organs and improve impaired functions, making them a key element in the research of therapies for kidney tissue repair and organ regeneration. In kidney transplantation, reperfusion injury can cause tissue destruction, leading to an initially low glomerular filtration rate and long-term impact on function by creating irreversible interstitial fibrosis. MSCs have proven useful in repairing early tissue injury in animal models of kidney, lung, heart, and intestine transplantation. The use of stem cell therapies in solid organ transplantation raises the question of whether autologous or allogeneic cells should be preferred. Adipose-derived stem cells (ASCs), characterized by the lack of HLA Class II molecules and low expression of HLA Class I and co-stimulatory signals, are considered immune-privileged. However, the actual risk of graft rejection associated with allogeneic ASCs remains unclear. It has been demonstrated that donor-derived ASCs can promote the development of Treg cells in vitro, and some degree of tolerance induction has been observed in vivo. Nevertheless, a study comparing the efficacy of autologous and allogeneic ASCs in a rat model with a total MHC mismatch for kidney transplantation showed that donor-derived administration of ASCs did not improve the grafts’ survival and was associated with increased mortality through an immunologically mediated mechanism. Given the lack of data, autologous ASCs appear to be a safer option in this research context. The aim of this review was to examine the differences between autologous and allogeneic ASCs in the context of their application in kidney transplantation therapies, considering potential immune reactions and therapeutic efficacy. Some have argued that ASCs harvested from end-stage renal disease (ESRD) patients may have lower regenerative potential due to the toxic effects of uremia, potentially limiting their use in transplantation settings. However, evidence suggests that the beneficial properties of ASCs are not affected by uremia or dialysis. Indeed, some investigators have demonstrated that ASCs harvested from chronic kidney disease (CKD) patients exhibit normal characteristics and function, maintaining consistent proliferative capacity and genetic stability over time, even after prolonged exposure to uremic serum Furthermore, no differences were observed in the response of ASCs to immune activation or their inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells between patients with normal or impaired renal function. This review presents the current achievements in stem cell research aimed at treating kidney diseases, highlighting significant progress and ongoing efforts in the development of stem cell-based therapies. Despite the encouraging results, further research is needed to overcome the current limitations and fully realize the potential of these innovative treatments. Advances in this field are crucial for developing effective therapies that can address the complex challenges associated with kidney damage and failure
Outcomes of Ixazomib Treatment in Relapsed and Refractory Multiple Myeloma: Insights from Croatian Cooperative Group for Hematologic Diseases (KROHEM)
No full textBackground and Objectives: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM).
Materials and Methods: This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023. Data on patient demographics, treatment regimens, and outcomes were collected and analysed using Kaplan–Meier survival curves and Cox proportional hazards models in R. The median age at ixazomib initiation was 66 years (range 40–91).
Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 15.4 months, while median overall survival (OS) was 28.2 months. Hematologic toxicities included anaemia (53%), neutropenia (50%), and thrombocytopenia (45%). Infective complications, primarily COVID-19 and pneumonia, were reported in 38% of patients. The safety profile was consistent with previous studies, indicating manageable adverse events. Ixazomib-based therapy is effective and well tolerated in a real-world Croatian RRMM population.
Conclusions: The findings align with clinical trial results, demonstrating the applicability of ixazomib in routine clinical practice. Further studies are needed to optimise treatment sequencing and improve patient outcomes
Hematologic Indices and Chronic Subdural Hematoma: A Single-Center Cohort Study
No full textObjective
Chronic subdural hematoma (cSDH) is common, predominantly affects the elderly, often recurs after treatment, and can have serious complications, including death. Inflammation plays an important role in cSDH and it has been previously shown that some laboratory indices are useful as prognostic markers. The aim was to research the role of hematologic and inflammatory markers in cSDH.
Materials and Methods
A single-center archival database review to retrieve data on cSDH cases operated on between 2018 and 2020, including: (1) sociodemography (age, gender), (2) clinics (Glasgow Coma Score [GCS], anticoagulants, chronic conditions), (3) laboratory (leukocyte, neutrophil, platelet, C-reactive protein, hemoglobin, red cell distribution width [RDW], neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio [PLR], systemic immune-inflammatory index [SII]), (4) cSDH (size, location, midline shift), and (5) treatment (craniotomy/craniostomy, drainage). Primary outcome was Glasgow Outcome Score (GOS) at discharge and at 1 year, and secondary outcomes were 1 year mortality, resurgery, and recurrence. Hematological and inflammatory indices were compared across two cSDH thickness groups.
Results
Seventy-two patients were included, 25 women and 47 men, median age 77 years. Seventeen (23.6%) patients had chronic anticoagulant treatment. The majority had a chronic comorbidity: 19 (26.4%) diabetes, 48 (66.7%) hypertension, and 56 (77.8%) other chronic diseases. Median preoperative GCS was 15. Median cSDH thickness was 22.9 mm, sidedness was equally distributed, and midline shift occurred in 60 (83.3 %) patients, with median midline shift of 8.4 mm. The majority of patients underwent a single craniostomy ( n = 44, 61.1%), and in all patients a subdural drainage was placed. Median GOS at discharge and at 1 year postoperatively was 5. Mortality was 11.1%, and 16.7% of patients were lost to follow-up. Within the 1-year follow-up, 27.8% of patients had disease recurrence, 25% underwent a repeat surgery. In the "above" versus "below" 15 mm cSDH thickness group there were significant differences in P count (211.5 vs. 279.5 × 10 9 /L, p = 0.009), RDW (13.3 vs. 12.6, p = 0.031), SII (1782 vs. 2653, p = 0.025), and PLR (26.2 vs. 36.7, p = 0.042).
Conclusion
Hematological indices bear a diagnostic and prognostic potential in cSDH management
Vancomycin-Resistant Enterococci: Current Understandings of Resistance in Relation to Transmission and Preventive Strategies
No full textDue to the limited treatment options and increased mortality rates, infection prevention and control strategies have been implemented for many years to mitigate dissemination of vancomycin-resistant enterococci (VRE) within healthcare settings. The overview provides an insight into the most recent research, particularly the pathogen’s resilience in the healthcare environment, and the critical need for infection control strategies, which are currently being scrutinized by some researchers. The notable resilience of enterococci to various environmental conditions highlights the necessity for investigations into innovative technologies capable of effectively targeting the biofilm produced by enterococci on hospital surfaces. A critical approach to traditional infection control strategies is becoming more accepted worldwide, taking into account the epidemiological situation in the given healthcare setting as well as specific characteristics of a patient. For certain high-risk patient populations, traditional infection control strategies including CP and screening should not be omitted. Additionally, further investigation into the resistance mechanisms of available antimicrobial agents is essential, as is research into their potential association with specific successful clones through WGS genotyping, to pre-emptively mitigate their spread before it escalates
Prevalence of allergic symptoms in the city of Zagreb and Lonjsko Polje
No full textUvod: Istraživanja pokazuju kako život u ruralnoj sredini ima zaštitni utjecaj na razvoj alergijskih bolesti.
Cilj: Cilj studije bio je usporediti prevalenciju simptoma astme, alergijskog rinitisa (AR) i atopijskog dermatitisa (AD) u školske djece Grada Zagreba i ruralne sredine Parka prirode Lonjsko polje (PPLP).
Materijali i metode: Prevalencija alergijskih simptoma utvrđena je pomoću upitnika Međunarodne studije alergije i astme u djece. Za analizu povezanosti čimbenika okoliša i alergijskih simptoma, korištena je multivarijatna logistička regresija.
Rezultati: U istraživanje je uključeno 1741 dijete. U prevalenciji simptoma astme između dvaju područja nije nađeno značajne razlike. U Gradu Zagrebu je značajno više djece imalo simptome AR-a tijekom posljednjih 12 mjeseci (35%) u odnosu na PPLP (29%) (p<0,001). U Gradu Zagrebu je zabilježena značajno viša prevalencija simptoma AD-a ikada (35,10%) u odnosu na PPLP (26,29%), (p=0,001), a značajno više djece imalo je i dijagnozu AD-a (29,30%) u odnosu na PPLP (16,60%), (p=0,001). Veći broj braće i sestara u kućanstvima, prisustvo tepiha i jas-tuka, te niži stupanj onečišćenja zraka, pretpostavljeni su čimbenici zaštite ruralnog okoliša.
Zaključak: Istraživanje je dokazalo zaštitni učinak života u PPLP na razvoj simptoma AR i AD-a.Background: Rural environment might have a protective effect in allergy.
Aim: The aim of the study was to compare the prevalence of asthma, atopic dermatitis (AD) and allergic rhinitis (AR) symptoms in the city of Zagreb and Natural Park Lonjsko polje (NPLP) and the role of environmental factors.
Methods: The prevalence of allergic symptoms was assessed using the International Study of Asthma and Allergy in Childhood questionnaire. Significance of the environmental factors was tested using logistic regression.
Results: 1741 children participated in the study. Between two regions, there was no significant difference in the prevalence of asthma symptoms. In the city of Zagreb, there was a higher prevalence of current AR symptoms (35%) comparing with the rural region (29%), (p=0.001). In all age groups, children from NPLP had lower risk for current AR symptoms, and of diagno-sed AR in the oldest age group (p<0.001). Prevalence of AD symptoms ever-in-the-lifetime was also higher in the urban region (35. 10% vs. 26.20%, p=0.001), as well as the prevalence of diagnosed AD (29.30 % vs. 16.60%, p=0.001). Logistic regression showed different role of the environmental factors in allergic entities in two regions, however, higher number of siblings and using carpets and feather pillows were more present in NPLP, and associated with lower risk of allergy.
Conclusion: This study showed a protective effect of living in NPLP on the symptoms of AR and AD