Veterinary medicine - Repository of PHD, master's thesis
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Impact of previous chronic statin therapy on mortality in patients with acute myocardial infarction treated with primary percutaneous coronary intervention
No full textProvedeno je prospektivno, kohortno istraživanje na seriji slučajeva koje je uključilo 2988 bolesnika (71.9% muškaraca), prosječne dobi 67 godina, koji su u razdoblju od 1. lipnja 2011. do 1. siječnja 2019. liječeni u Kliničkom bolničkom centru Sestre milosrdnice perkutanom koronarnom intervencijom zbog prvog infarkta miokarda. Kao primarni cilj istraživanja ispitivan je utjecaj ranije kronične terapije statinima na smrtnost bolesnika s infarktom miokarda. Medijan praćenja iznosio je 61 mjesec. Bolesnici su podijeljeni u dvije skupine, a ovisno o prethodnoj terapiji statinom. Analizirana je ukupna smrtnost (do kraja perioda praćenja) i kratkoročna smrtnost (unutar 30 dana od infarkta miokarda). Zasebno je analizirana opća i kardiovaskularna smrtnost. Od 2988 bolesnika, 420 (14.1%) je prethodno liječeno statinom, a u navedenoj je skupini zabilježena statistički značajnija opterećenost ranije utvrđenom aterosklerotskom bolesti i kardiovaskularnim komorbiditetima. Rezultati istraživanja nisu pokazali statistički značajnu razliku u smrtnosti među promatranim skupinama, kako kratkoročnoj tako dugoročnoj, čime je potvrđena nul-hipoteza. Promatrajući opću smrtnost, uočeno je da bolesnici prethodno liječeni statinima tijekom perioda praćenja umiru ranije od onih koji prethodno nisu liječeni statinima. Kao neovisni prediktori smrtnosti izdvojeni su: dob bolesnika, šećerna bolest, periferna arterijska bolest, ventrikulska tahikardija i visoki Killip stupanj u trenutku prijema. Kada se promatrao tip infarkta i angiografske karakteristike, uočeno je da su bolesnici liječeni statinima češće imali NSTEMI i angiografski neokluzivni tip infarkta, koji je ujedno bio i prediktor smrtnosti. Među laboratorijskim nalazima i rezultatima oslikavanja vrijednosti hemoglobina i ejekcijske frakcije lijevog ventrikula su se pokazale kao neovisni prediktori smrtnosti. Ovo istraživanje pokazalo je kako SCORE2 sustav dobro predviđa rizik smrti bilo kojeg uzroka bolesnika nakon infarkta miokarda, neovisno o prethodnom liječenju statinima. I visokorizični i nevisokorizični bolesnici imaju jednaku smrtnost tijekom perioda praćenja, neovisno o ranijem liječenju statinom.A prospective cohort study was conducted on a series of cases involving 2988 patients (71.9% male), with an average age of 67 years, who were treated at the Sestre milosrdnice University Hospital from June 1, 2011, to January 1, 2019, with percutaneous coronary intervention due to their first myocardial infarction.
The primary aim of the study was to examine the impact of prior chronic statin therapy on mortality in patients with myocardial infarction. The median follow-up period was 61 months. Patients were divided into two groups based on previous statin therapy. Overall mortality (until the end of the follow-up period) and short-term mortality (within 30 days of myocardial infarction) were analyzed. All-cause and cardiovascular mortality were analyzed separately. Out of the 2988 patients studied, 420 (14.1%) had previously been treated with statins, and this group showed a statistically significant higher burden of previously diagnosed atherosclerotic disease and cardiovascular comorbidities. The results of the study did not show a statistically significant difference in mortality between the observed groups, both short-term and long-term, thus confirming the null hypothesis. Observing all-cause mortality, it was noted that patients previously treated with statins died earlier during the follow-up period than those who had not been previously treated with statins. Independent predictors of mortality included: patient age, diabetes mellitus, peripheral arterial disease, ventricular tachycardia, and high Killip class at admission. When considering the type of infarction and angiographic characteristics, it was noted that patients treated with statins more often had NSTEMI and angiographically non-occlusive type of infarction, which was also a predictor of mortality. Among the laboratory findings and imaging results, hemoglobin levels and ejection fraction were shown to be independent predictors of mortality. This study demonstrated that the SCORE2 system effectively predicts all-cause mortality, regardless of prior statin use. Both high-risk and non-high-risk patients did not show different mortality rates depending on prior statin therapy
Clinical utility of [68Ga]Ga-PSMA-11 PET/CT in initial staging of patients with prostate cancer and importance of intraprostatic SUVmax values
No full textBackground: As in disease recurrence, providing clinicians with the exact extent of the disease at the time of initial diagnosis is key in the management and individual treatment of prostate cancer (PC) patients. Intending to examine the usefulness of gallium- 68 PSMA-11 positron emission tomography/computed tomography ([68Ga]Ga-PSMA-11 PET/CT) and to determine if there is a correlation between prostate-specific antigen (PSA) serum values, WHO/ISUP (World Health Organization/International Society of Urological Pathology's) grade group of the tumor and SUVmax (maximized standardized uptake value) values we retrospectively analyzed PET/CT studies performed for initial staging of the disease.
Patients and methods: We retrospectively evaluated 34 studies of patients who underwent [68Ga]Ga-PSMA-11 PET/CT as part of the initial staging of prostate cancer. All patients had prostate cancer confirmed by histological assessment after biopsy and had Gleason score and PSA serum values obtained. The mean PSA value was 33.8 ± 40.9 nmol/L (range 2.2-232).
Results: Nineteen patients had extended disease (55.9%). The mean SUVmax in prostate lesions was 19.5 ± 12.6. The mean value of SUVmax of PET studies in the high-risk group was significantly higher than those of low risk (23.5 ± 13.2 and 10.6 ± 5.4, p < 0.05). A positive correlation was observed between the ISUP group and SUVmax value of prostate lesions (Pearson's r = 0.557, p < 0.01). A positive correlation was also found in the comparison between PSA values and SUVmax (Pearson's r = 0.34, p < 0.05).
Conclusions: In our study, [68Ga]Ga-PSMA-11 PET/CT scans detected the extended disease in more than half of the patients. Locating disease beyond the prostate gland allowed better informed clinical decisions and modified treatment. A positive correlation was found between intraprostatic SUVmax values and the ISUP group of prostate cancer. High-risk patients had SUVmax values that were significantly higher than those of low-risk patients. The correlation between the Gleason score and SUVmax value can be explained by the increased intensity of PSMA expression as the tumor grade increases
The Impact of Latent Cytomegalovirus Infection on Spontaneous Abortion History and Pregnancy Outcomes in Romanian Pregnant Women
No full textCytomegalovirus (CMV), a DNA virus that belongs to the Orthoherpesviridae family, infects 40–100% of people. Primary/non-primary CMV infection during pregnancy could cause fetal disabilities. After primary infection, CMV causes a latent infection and resides in cells of the myeloid compartment (CD34+, monocytes). Few studies have analyzed the impact of latent CMV infections on miscarriage history, pregnancy complications, and neonatal outcomes.
Methods: Serum samples from 806 pregnant women (28.29 ± 4.50 years old) who came for a consultation at the Timisoara Clinical Emergency City Hospital between 2008 and 2010 were tested for anti-CMV IgM/IgG antibodies, and data about demography, obstetrical history, pregnancy complications, birth, and neonate were collected. The data were compared between the groups with and without latent CMV infection, and statistical significance was calculated.
Results: We did not find a difference regarding cesarean section (OR = 0.916, p = 0.856), placental abruption (OR = 1.004, p = 1.00), pregnancy-induced hypertension rate (OR = 1.078, p = 1.00), secondary sex ratio (0.882, p = 0.857), APGAR score (p = 0.225), gestational age at birth (p = 0.434), or birth weight (p = 0.365). A borderline significant difference was found regarding the presence of miscarriage history: OR = 8.467, p = 0.051.
Conclusions: The presence of latent CMV infection does not affect the likelihood of complications in healthy women. A borderline significantly higher prevalence of miscarriage history was found in women with latent CMV infection
Detection of Macrolide and/or Fluoroquinolone Resistance Genes in Mycoplasma genitalium Strains Isolated from Men in the Northwest Region of Croatia in 2018–2023
No full textMycoplasma genitalium (M. genitalium) poses a significant public health challenge due to its association with non-gonococcal urethritis (particularly in men) and antimicrobial resistance. However, despite the prevalence of M. genitalium infections and the rise in resistance rates, routine testing and surveillance remain limited. This is the first study from Croatia that aimed to assess the prevalence and trends of resistance in M. genitalium strains isolated from male individuals by detecting macrolide and fluoroquinolone resistance genes. The study also aimed to explore the factors associated with resistance and changes in resistance patterns over time. Urine samples collected from male individuals in the Zagreb County and northwest region of Croatia between 2018 and 2023 were tested for M. genitalium with the use of molecular methods. Positive samples were subjected to DNA extraction and multiplex tandem polymerase chain reaction (MT-PCR) targeting genetic mutations associated with macrolide (23S rRNA gene) and fluoroquinolone (parC gene) resistance. Of the 8073 urine samples tested from 6480 male individuals (and following the exclusion of repeated specimens), we found that the prevalence of M. genitalium infection was 2.2%. Macrolide resistance was observed in 60.4% of strains, while fluoroquinolone resistance was found in 19.2%. Co-resistance to both antibiotics was present in 18.2% of cases. A statistically significant increase in fluoroquinolone resistance was noted over the study period (p = 0.010), but this was not evident for azithromycin resistance (p = 0.165). There were no statistically significant differences in resistance patterns between age groups, whereas re-testing of patients revealed dynamic changes in resistance profiles over time. The high burden of macrolide resistance and increasing fluoroquinolone resistance underscore the urgent need for comprehensive resistance testing and surveillance programs. The implementation of resistance-guided treatment strategies, along with enhanced access to molecular diagnostics, is pivotal for effectively managing M. genitalium infections
Proinflammatory Chemokine Levels in Cerebrospinal Fluid of Patients with Neuroinvasive Flavivirus Infections
No full textTick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are the most important neuroinvasive arboviruses detected in Europe. In this study, we analyzed cerebrospinal fluid (CSF) concentrations of 12 proinflammatory chemokines (CCL2, CCL3, CCL4, CCL11, CCL17, CCL20, CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, and CXCL11) in 77 patients with neuroinvasive diseases (NIDs). Flavivirus infection was confirmed in 62 patients (TBEV and WNV in 31 patients each), while in 15 patients the etiology of NID was not determined (NDE). Similar patterns of high-level expression of chemokines regulating monocyte/macrophage responses (CCL2), neutrophil recruitment (CXCL1 and CXCL8), and interferon-inducible chemoattractants for leukocytes (CXCL10 and CXCL11) have been observed in WNV and TBEV groups. None of the tested chemokines significantly differed between patients with TBEV or WNV. Concentrations of CCL17, CCL20, CXCL5, CXCL10, and CXCL11 were significantly lower in both WNV and TBEV groups compared to NID NDE patients. The logistic regression model showed that CSF concentrations of CXCL11, CXCL5, and CXCL10 could potentially be used for the classification of patients into the WNV or TBEV group versus groups with other NIDs. This study identified, for the first time, similar patterns of CSF chemokine expression in WNV and TBEV infections, suggesting common immunopathogenic mechanisms in neuroinvasive flavivirus infections that should be further evaluated
Evaluation of Absolute Neutrophil, Lymphocyte and Platelet Count and Their Ratios as Predictors of Thrombotic Risk in Patients with Prefibrotic and Overt Myelofibrosis
No full textAim: To investigate the prognostic contribution of absolute neutrophil (ANC), lymphocyte (ALC), platelet count and their ratios, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR), to thrombotic risk in patients with prefibrotic and overt fibrotic myelofibrosis (MF). Methods: We retrospectively analyzed a cohort of 256 patients with prefibrotic (85 patients) and overt fibrotic MF (171 patients) treated in six Croatian hematological centers.
Results: Prefibrotic compared to overt fibrotic MF patients presented with significantly higher ALC, platelet count and PLR, and experienced longer time to thrombosis (TTT). Among prefibrotic patients, ANC > 8.33 × 109/L (HR 13.08, p = 0.036), ALC > 2.58 × 109/L (HR 20.63, p = 0.049) and platelet count > 752 × 109/L (HR 10.5, p = 0.043) remained independently associated with shorter TTT. Among overt fibrotic patients, ANC > 8.8 × 109/L (HR 4.49, p = 0.004), ALC ≤ 1.43 × 109/L (HR 4.15, p = 0.003), platelet count ≤ 385 × 109/L (HR 4.68, p = 0.004) and chronic kidney disease (HR 9.07, p < 0.001) remained independently associated with shorter TTT.
Conclusions: Prognostic properties of ANC, ALC and platelet count are mutually independent and exceed those of NLR and PLR regarding thrombotic risk stratification. ALC and platelet count associate in opposite directions with thrombotic risk in prefibrotic and overt fibrotic MF patients
Ketamine induces multiple individually distinct whole-brain functional connectivity signatures
No full textBackground: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects.
Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets.
Results: We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.
Conclusions: These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry
Pulsating Extremely Low-Frequency Electromagnetic Fields Influence Differentiation of Mouse Neural Stem Cells towards Astrocyte-like Phenotypes: In Vitro Pilot Study
No full textEven though electromagnetic fields have been reported to assist endogenous neurogenesis, little is known about the exact mechanisms of their action. In this pilot study, we investigated the effects of pulsating extremely low-frequency electromagnetic fields on neural stem cell differentiation towards specific phenotypes, such as neurons and astrocytes. Neural stem cells isolated from the telencephalic wall of B6(Cg)-Tyrc-2J/J mouse embryos (E14.5) were randomly divided into three experimental groups and three controls. Electromagnetic field application setup included a solenoid placed within an incubator. Each of the experimental groups was exposed to 50Hz ELF-EMFs of varied strengths for 1 h. The expression of each marker (NES, GFAP, β-3 tubulin) was then assessed by immunocytochemistry. The application of high-strength ELF-EMF significantly increased and low-strength ELF-EMF decreased the expression of GFAP. A similar pattern was observed for β-3 tubulin, with high-strength ELF-EMFs significantly increasing the immunoreactivity of β-3 tubulin and medium- and low-strength ELF-EMFs decreasing it. Changes in NES expression were observed for medium-strength ELF-EMFs, with a demonstrated significant upregulation. This suggests that, even though ELF-EMFs appear to inhibit or promote the differentiation of neural stem cells into neurons or astrocytes, this effect highly depends on the strength and frequency of the fields as well as the duration of their application. While numerous studies have demonstrated the capacity of EMFs to guide the differentiation of NSCs into neuron-like cells or β-3 tubulin+ neurons, this is the first study to suggest that ELF-EMFs may also steer NSC differentiation towards astrocyte-like phenotypes
Specificities in the Structure of the Cartilage of Patients with Advanced Stages of Developmental Dysplasia of the Hip
No full textDevelopmental dysplasia of the hip (DDH) presents varying degrees of femoral head dislocation, with severe cases leading to the formation of a new articular surface on the external side of the iliac bone—the neoacetabulum. Despite conventional understanding suggesting otherwise, a tissue resembling hyaline cartilage is found in the neoacetabulum and acetabulum of Crowe III and IV patients, indicating a potential for hyaline cartilage development without mechanical pressure. To test this theory, acetabular and femoral head cartilage obtained from patients with DDH was stained with hematoxylin–eosin and toluidine blue. The immunohistochemical analysis for collagen types II and VI and aggrecan was performed, as well as delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) analysis on a 7.0 T micro-MRI machine. The results obtained from DDH patients were compared to those of the control groups. Hyaline cartilage was found in the neoacetabulum and the acetabulum of patients with DDH. The nature of the tissue was confirmed with both the histological and the MRI analyses. The results of this study proved the presence of hyaline cartilage in patients with DDH at anatomical regions genetically predisposed to be bone tissue and at regions that are not subjected to mechanical stress. This is the first time that the neoacetabular cartilage of patients with advanced stages of DDH has been characterized in detail
Unmet needs in EGFR exon 20 insertion mutations in Central and Eastern Europe: reimbursement, diagnostic procedures, and treatment availability
No full textLung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3-2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as "typical" EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations.This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions.The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR, ALK, RET, MET, NTRK, and ROS1, necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations