Veterinary medicine - Repository of PHD, master's thesis
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Predictive Model for Sperm Presence in Testes of Azoospermic Men Based on Magnetic Resonance Imaging
No full textU populaciji neplodnih muškaraca, 15 % ih ima azoospermiju i ti se muškarci upućuju na biopsiju sjemenika koja je uspješna u oko 50 % pacijenata. Cilj ove studije bio je izraditi prediktivni model za prisutnost spermija u tkivu sjemenika temeljen na ex-vivo podacima dobivenim snimanjem magnetskom rezonancijom (MRI) i spektroskopijom, kao i podacima dobivenim standardnom dijagnostičkom obradom. Uzorci humanog tkiva sjemenika dobiveni biopsijom podvrgnuti su 7T MRI koje je uključivalo T2 mapiranje, snimanje difuzijskog tenzora (DTI), snimanje prijenosa magnetizacije (MTI) i spektroskopiju magnetske rezonancije
(MRS). Uzorci su zatim histološki obrađeni i analizirani. Provedena je multivarijatna logistička regresija kako bi se procijenio odnos između 12 nezavisnih varijabli i prisutnosti spermija. Nezavisne varijable korištene za konstrukciju prediktivnog modela bile su T2, ADC, FA, MTR, koncentracije kolina, kreatina, laktata, glutamata i mioinozitola, razine FSH i LH i povijest kriptorhizma kod pacijenta. Površina ispod ROC krivulje za najuspješniji model bila je 0,9738 s negativnom prediktivnom vrijednosti od 100 %. Prisutnosti spermija u tkivu sjemenika moguće je predvidjeti korištenjem prediktivnog modela temeljenog na magnetskoj rezonanciji,
a model je potrebno validirati na in vivo podacima za kliničku upotrebu.15 % of infertile men have azoospermia, and those men are referred for a testicular biopsy, which is successful in around 50 % of patients. The objective of this study was to construct a predictive model for sperm presence based on ex-vivo magnetic resonance imaging (MRI) and spectroscopy data, as well as data obtained through the standard diagnostic evaluation of azoospermia. Samples of human testicular tissue were obtained via testicular biopsy and underwent 7T MRI, specifically T2 mapping, diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and magnetic resonance spectroscopy (MRS). Samples were then histologically processed and analyzed. Multivariate logistic regression was performed to evaluate the relationship between 12 independent variables and sperm presence. The independent variables used for the construction of the predictive model were T2, ADC, FA, MTR, concentrations of choline, creatine, lactate, glutamate, and myo-inositol, FSH and LH levels and patient history of cryptorchidism. The predicted area under the ROC curve for the most successful model was 0.9738, with a negative predictive power of 100 %. Sperm presence in testicular tissue can be predicted by using a predictive model based on magnetic resonance imaging, and the model should be validated with in-vivo data for clinical use
Influence of remission of Cushing's syndrome on parameters of metabolic syndrome
No full textCilj ovog istraživanja bio je ispitivanje promjene metaboličkih parametara u bolesnika s Cushingovim sindromom prije i nakon liječenja, odnosno ispitivanje utjecaja remisije bolesti na pojedine komponente metaboličkog sindroma te pridružene bolesti. Dodatni cilj bio je analizirati razlike između ACTH-ovisnog i ACTH-neovisnog CS, pojavnost kardiovaskularnih i tromboembolijskih događaja, učinak remisije na kardiovaskularni rizik, kvalitetu života te oporavak osovine hipotalamus-hipofiza-nadbubrežna žlijezda. U istraživanje je uključeno 78 bolesnika liječenih u Zavodu za endokrinologiju KBC Zagreb zbog prekomjernog lučenja kortizola uzrokovanog ACTH-ovisnim ili ACTH-neovisnim Cushingovim sindromom u periodu od 2011. do 2017. god. Medijan dobi ispitanika bio je 46 godina, a 83,3% ispitanika su bile žene. Najčešće se radilo o ACTH-ovisnom CS ili Cushingovoj bolesti u 69,2% bolesnika.
Najčešće pridružene bolesti u ispitivanoj skupini su bile: arterijska hipertenzija (76,9%), hiperlipidemija (46,2%), pretilost (42%) te šećerna bolest (32%) i njihova pojavnost bila je značajno veća nego u općoj populaciji. Nakon operativnog liječenja je 87,2% bolesnika postiglo remisiju bolesti. Udio bolesnika u remisiji u ACTH-ovisnoj skupini iznosio je 81,5%, a u ACTH-neovisnoj skupini 100%. Šest mjeseci nakon postizanja remisije bolesti došlo je do značajnog smanjenja odnosno poboljšanja glukoze u plazmi (p=0,001), HbA1c (p=0,007), ukupnog kolesterola (p=0,032), HDL kolesterola (p=0,001) dok smanjenje vrijednosti LDL kolesterola i triglicerida nije doseglo razinu statističke značajnosti. Također je došlo do značajnog smanjenja pojavnosti šećerne bolesti uz nesignifikantno smanjenje pojavnosti arterijske hipertenzije, debljine i hiperlipidemije za ukupnu populaciju. Međutim kada se gledala razlika između ACTH-ovisnog i ACTH-neovisnog CS nađena je značajna razlika u svim odrednicama metaboličkog sindroma šest mjeseci nakon remisije. Također su bolesnici u remisiji imali statistički značajno smanjenje kardiovaskularnog rizika iz umjerenog u graničan rizik u usporedbi s bolesnicima s aktivnom bolesti (p=0,009).
Što se tiče kvalitete života prije operacije su bolesnici s ACTH-ovisnim CS imali bolju pokretljivost (p=0,016), bolje skrbili o sebi (p=0,014) te bolje izvršavali uobičajene aktivnosti (p=0,026) u odnosu na bolesnike s ACTH-neovisnim CS. U remisiji nije bila značajna razlika u parametrima kvalitete života izuzev granične značajnosti za uobičajenu aktivnost u korist ACTH-ovisnog CS (p=0,059). Vrijeme oporavka osovine hipotalamus-hipofiza-nadbubrežna žlijezda bila je duža u bolesnika s ACTH-neovisnom CS međutim bez statističke značajnosti (p=0,172).
Na temelju ovog istraživanja možemo zaključiti da remisija CS dovodi do značajnog smanjenja opsega struka te bolje regulacije krvnog tlaka i glikemije kao i do smanjenja koncentracije ukupnog kolesterola i HDL kolesterola, međutim ne dovodi do značajne promjene u koncentraciji LDL kolesterola i triglicerida. Procjenjujući kardiovaskularni rizik pomoću Heart risk kalkulatora, remisija CS dovodi do značajnog smanjenja kardiovaskularnog rizika u odnosu na rizik za vrijeme trajanja aktivne bolesti.This study aimed to investigate the changes in metabolic parameters in patients with Cushing's syndrome before and after treatment, especially the influence of disease remission on each component of the metabolic syndrome and its associated comorbidities. An additional purpose of the study was to investigate the differences between ACTH-dependent and ACTH-independent CS, the occurrence of cardiovascular and thromboembolic events, the influence of remission on cardiovascular risk assessment, quality of life, and the recovery of the hypothalamic-pituitary-adrenal axis (HPA). The study comprised 78 patients treated for ACTH-dependent and ACTH-independent Cushing's syndrome in the period from 2011 to 2017 at the Department of Endocrinology, University Hospital Center Zagreb. The median age was 46 years and 83.3% of the patients were female. ACTH-dependent CS was present in 69,2% of the patients.
The most common comorbidities in our cohort included arterial hypertension (76,9%), hyperlipidemia (46,2%), obesity (42%), and diabetes (32%) which was more common than in the general population.
After surgical treatment 87,2% of the patients achieved remission. Patients with ACTH-dependent CS achieved remission in 81,5% of the cases compared to 100% in patients with ACTH-independent CS. Six months after remission there was a significant change and improvement of glucose levels in the blood (p=0,001), HbA1c levels (p=0,007), total cholesterol (p=0,032), and HDL cholesterol levels (p=0,001) whereas levels of LDL cholesterol and triglycerides did not achieve statistical significance. Among the general cohort, there was a significant decrease in the incidence of diabetes and a nonsignificant decrease in hypertension, obesity, and hyperlipidemia.
Comparing ACTH-dependent and ACTH-independent CS six months after remission there was a significant decrease of all comorbidities. There was also a significant decrease in cardiovascular risk calculating heart risk score (p=0.009). Quality of life did not change significantly after remission except for borderline significant improvement of usual activities in the ACTH-dependent CS cohort (p=0,059).
HPA-axis recovery was longer in the ACTH-independent CS cohort but without statistical significance (p=0,172). We can conclude that remission of CS leads to a significant reduction in waist circumference and better regulation of blood pressure and glycemia, as well as to a decrease in the concentration of total cholesterol and HDL cholesterol, however, it does not lead to a significant change in the concentration of LDL cholesterol and triglycerides. Assessing cardiovascular risk using the Heart risk calculator, CS remission leads to a significant reduction in cardiovascular risk compared to the risk during active disease
The effect of BNT162b2 and Ad26.CoV2.S coronavirus vaccines on the parameters of hemostatis and inflammation
No full textGlavni cilj ovog prospektivnog opservacijskog istraživanja bio je ispitati utjecaj mRNA BNT162b2 i vektorskog Ad26.CoV2.S cjepiva protiv SARS-CoV-2 na pokazatelje zgrušavanja i upale.
Istraživanje je obuhvatilo 87 ispitanika u mRNA skupini (prosječne dobi 35 god, udio žena 59% ) i 84 u vektorskoj skupini (prosječne dobi 44 godine, udio muškaraca 52%) kojima su određivani laboratorijski pokazatelji (TAT, F1+2, d-dimeri, IL-6, veliki ET-1, fibrinogen, VWF:Ac, CRP, KKS) prije, 7 i 14 dana nakon cijepljenja vektorskim, odnosno prije, 7 i 14 dana nakon 1. i 2. doze mRNA cjepiva.
Nakon cijepljenja zabilježen je porast vrijednosti d-dimera (P=0,004) i pad aktivnosti VWF-a u obje skupine (P<0,001 u) te porast CRP-a (P=0,006) u vektorskoj i velikog ET-1 (P<0,001) u mRNA grupi. Veći CRP (P=0,014) zabilježen je 7 dana nakon cijepljenja vektorskim cjepivom u odnosu na mRNA cjepivo. Kod svih ispitanika isključena je prisutnost protutijela na trombociti faktor 4.
Zaključno, statistički značajne razlike pokazatelja zgrušavanja i upale u našem istraživanju mogu se pripisati opće poznatoj i očekivanoj blagoj reakciji na cijepljenje SARS-CoV-2 cjepivima. Niti jedan ispitanik nije imao tromboembolijski incident u 6-mjesečnom periodu praćenja nakon cijepljenja.The main aim of our study was to investigate the effect of mRNA BNT162b2 and vector Ad26.CoV2.S vaccine against SARS-CoV-2 on the markers of hemostasis and inflammation.
The study included 87 subjects in the mRNA group (median age 35 years, 59% of women) and 84 (median age 44 years, 52% of men) in the vector group. All the laboratory parameters (TAT, F1+2, d-dimers, VWF:Ac, fibrinogen, big ET-1, CRP, CBC) were investigated before, 7 and 14 days after the vaccination in the vector group and before, 7 and 14 day after the 1st and 2nd dose in the mRNA group.
After vaccination with both vaccines higher levels of d-dimers (P=0.004) and lower levels of VWF:Ac (P<0,001) were noted. CRP levels were eleveted (P=0.006) in the vector group while in the mRNA group, higer levels of big ET-1 (P<0,001) were noted. Higher CRP levels (P=0.014) were present 7 days after the vector vaccine immunisation in comparisson with the mRNA vaccine. All the study participants tested negative for platelet factor 4 antibodies.
In conclusion, although statistically significant changes in the parameters of hemostatasis and inflammation have been obtained, they remained clinically irrelevant (no thromoembolic events have been noted in the 6-months surveillance period) and can be contributed to the wellknown reaction to the vaccination
Plan upravljanja istraživačkim podacima - HRZZ IP2020-02 - 5960
No full textOpis plana upravljanja istraživačkim podacima generiranima u sklopu projekta "Utjecaj koštanog morfogenetskog proteina 3 (BMP3) na regeneraciju koštanog tkiva - BON3gen" financiranog od HRZZ-a, u sklopu poziva IP-2020-02
Progresivna multifokalna leukoencefalopatija u bolesnika koji žive s HIV-om
No full textHIV infection is a healthcare problem worldwide, leading to opportunistic infections such as candidiasis, Kaposi sarcoma, and PML. There are several prevention programs and campaigns that aim to reduce the burden of HIV infection and AIDS. However, they remain prevalent and are associated with complications, especially in late presenters.
PML, an AIDS-defining disease caused by the JC virus, presents with neurological symptoms due to demyelination of the CNS. Although in most cases, diagnosis is done by a combination of clinical features, imaging, and CSF analysis, sometimes false negative results can arise, which can delay treating those patients. Therefore, an interdisciplinary team is essential for the correct management of patients with non-classical diagnostic results. In those cases, PML cannot be ruled out, and further tests that include brain biopsy are required.
Those points will be presented in a case report and supported by similar cases from literature, emphasizing the importance of comprehensive evaluation in late presenters with neurological manifestations of PML.Infekcija HIV-om je zdravstveni problem širom svijeta, što dovodi do oportunističkih infekcija poput kandidijaze, Kaposijevog sarkoma i PML-a. Postoji nekoliko programa prevencije i kampanja koje imaju za cilj smanjenje opterećenja infekcijom HIV-om i AIDS-om. Međutim, i dalje su prisutni i povezani su s komplikacijama, posebno kod kasno otkrivenih pacijenata.
PML, bolest koja definira AIDS i uzrokovana je JC virusom, manifestira se neurološkim simptomima zbog demijelinizacije CNS-a. Iako se u većini slučajeva dijagnoza postavlja kombinacijom kliničkih obilježja, snimanja i analize likvora, ponekad se mogu pojaviti lažno negativni rezultati, što može odgoditi liječenje tih pacijenata. Stoga je interdisciplinarni tim ključan za ispravno upravljanje pacijentima s neklasičnim dijagnostičkim rezultatima. U tim slučajevima, PML se ne može isključiti, a potrebna su daljnja ispitivanja koja uključuju biopsiju mozga.
Ti će se aspekti predstaviti u prikazu slučaja, kao i potkrijepiti sličnim slučajevima iz literature, čime se naglašava važnost sveobuhvatne procjene kod kasno otkrivenih pacijenata s neurološkim manifestacijama PML-a
Očuvanje plodnosti
No full textFertility preservation describes the treatments and procedures performed in medicine to preserve or protect an individual's future capacity to bear biological children. Most of the time it includes the process of storing oocytes, embryos, or reproductive tissue for later conception. Fertility preservation may be performed prior to fertility-altering treatment, such as chemotherapy, radiotherapy, hormonal therapy, HER2 therapy and immunotherapy or to people who want to postpone having children for social reasons until a later age, when fertility may have declined. This comprehensive review explores the various reasons for fertility preservation and emphasizes the importance of considering fertility preservation options early. It covers fertility preservation technique types. The review discusses fertility preservation in the context of breast cancer, endometriosis, systemic lupus erythematosus and social freezing, offering valuable insights into this crucial aspect of reproductive health. It serves as a valuable resource in understanding the complex landscape of fertility preservation and its impact on family planning.Očuvanje plodnosti opisuje tretmane i postupke koji se izvode u medicini kako bi se očuvala ili zaštitila buduća sposobnost pojedinca da rađa biološku djecu. Većinu vremena uključuje proces pohranjivanja jajnih stanica, embrija ili reproduktivnog tkiva za kasnije začeće.
Očuvanje plodnosti može se provesti prije liječenja koje mijenja plodnost, kao što je kemoterapija, radioterapija, hormonska terapija, HER2 terapija i imunoterapija ili za osobe koje žele odgoditi rađanje djece iz društvenih razloga do kasnije dobi, kada je plodnost možda smanjena.
Ovaj opsežni pregled istražuje različite razloge za očuvanje plodnosti i naglašava važnost ranog razmatranja opcija za očuvanje plodnosti. Obuhvaća vrste tehnika očuvanja plodnosti. Recenzija govori o očuvanju plodnosti u kontekstu raka dojke, endometrioze, sistemskog eritemskog lupusa i socijalnog zamrzavanja, nudeći dragocjene uvide u ovaj ključni aspekt reproduktivnog zdravlja. Služi kao vrijedan izvor za razumijevanje složenog krajolika očuvanja plodnosti i njegovog utjecaja na planiranje obitelji
Traditional risk factors and premature acute coronary syndromes in South Eastern Europe: a multinational cohort study
No full textBackground: The age-standardized death rates under 65 years from ischemic heart disease in South Eastern Europe are approximately twice as high than the Western Europe average, but the reasons are not completely recognized. The aim of the present study was to address this issue by collecting and analyzing data from a large, multinational cohort.
Methods: We enrolled 70,953 Caucasian patients with first acute coronary syndrome, from 36 urban hospital in 7 South Eastern European countries and assessed their life expectancy free of acute coronary syndrome and mortality within 30 days after hospital admission from acute coronary syndrome as estimated in relation to dichotomous categories of traditional risk factors (current smoking, hypertension, diabetes and hypercholesterolemia) stratified according to sex.
Findings: Compared with patients without any baseline traditional risk factors, the presence of all four risk factors was associated with a 5-year shorter life expectancy free of acute coronary syndrome (women: from 67.1 ± 12.0 to 61.9 ± 10.3 years; r = -0.089; p < 0.001 and men: from 62.8 ± 12.2 to 58.9 ± 9.9 years; r = -0.096; p < 0.001). Premature acute coronary syndrome (women <67 years and men <63 years) was remarkably related to current smoking and hypercholesterolemia among women (RRs: 3.96; 95% CI: 3.72-4.20 and 1.31; 95% CI: 1.25-1.38, respectively) and men (RRs: 2.82; 95% CI: 2.71-2.93 and 1.39; 95% CI: 1.34-1.45, respectively). Diabetes was most strongly associated with death from premature acute coronary syndrome either in women (RR: 1.52; 95% CI: 1.29-1.79) or men (RR: 1.63; 95% CI: 1.41-1.89).
Interpretation: Public health policies in South Eastern Europe should place significant emphasis on the four traditional risk factors and the associated lifestyle behaviors to reduce the epidemic of premature ischemic heart disease
Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients
No full textBACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019 (COVID-19) but its full correlation with COVID-19 infection remains unknown. AIM To identify acute pancreatitis’ occurrence, clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.
METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19. Data were obtained from hospital electronic medical records. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.
RESULTS Four hundred and eight out of 1432 (28.49%) patients who received a renal allograft developed COVID-19 disease. The analyzed cohort included 321 patients (57% males). One hundred and fifty patients (46.7%) received at least one dose of the anti-SARS-CoV-2 vaccine before the infection. One hundred twenty-five (39.1%) patients required hospitalization, 141 (44.1%) developed pneumonia and four patients (1.3%) required mechanical ventilation. Treatment included immunosuppression modification in 233 patients (77.1%) and remdesivir in 53 patients (16.6%), besides the other supportive measures. In the study cohort, only one transplant recipient (0.3%) developed acute pancreatitis during acute COVID-19, presenting with abdominal pain and significantly elevated pancreatic enzymes. She survived without complications with a stable kidney allograft function.
CONCLUSION Although rare, acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients. The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research
In Association with Other Risk Factors, Smoking Is the Main Predictor for Lower Transcutaneous Oxygen Pressure in Type 2 Diabetes
No full textType 2 diabetes mellitus (T2DM) significantly increases the risk of peripheral artery disease (PAD), and diabetes is the leading cause of nontraumatic amputations. This study investigated the risk factors for transcutaneous oxygen pressure (TcPO2) in T2DM, a noninvasive method to quantify skin oxygenation and the underlying microvascular circulation. The study included 119 T2DM patients (91 male/28 female). TcPO2 measurements were conducted with the Tina TCM4 Series transcutaneous monitor (Radiometer, Copenhagen, Sweden) and skin electrodes. Patients with TcPO2 < 40 mmHg were younger (p = 0.001), had significantly higher systolic blood pressure (SBP) (p = 0.023), glycated hemoglobin (HbA1c) (p = 0.013), fasting plasma glucose (fPG) (p = 0.038), total cholesterol (p = 0.006), LDL cholesterol (p = 0.004), and had more frequent smoking habits (p = 0.001) than those with TcPO2 ≥ 40 mmHg. The main predictors for the TcPO2 value (R2 = 0.211) obtained via stepwise regression analysis were age, smoking, SBP, HbA1c, fPG, and total and LDL cholesterol. Among all the listed predictors, smoking, HbA1c, and LDL cholesterol were found to be the most significant, with negative parameter estimates of −3.051310 (p = 0.0007), −2.032018 (p = 0.0003), and −2.560353 (p = 0.0046). The results of our study suggest that in association with other risk factors, smoking is the main predictor for lower TcPO2 in T2DM
The assessment of tumor-infiltrating lymphocytes in invasive apocrine carcinoma of the breast in relation to the HER2 status
No full textIn the current study, we assessed the prevalence and molecular features of HER2-low phenotype in the apocrine carcinomas of the breast (ApoCa) and its relationship with tumor-infiltrating lymphocytes (TILs). A cohort of 64 well-characterized therapy-naïve ApoCa was used. The TIL distribution was assessed using the hematoxylin and eosin whole slide/scanned images following the international TILs working group recommendations. Next-generation sequencing (NGS) was performed in a subset of HER2-low ApoCa. All patients were women, with a mean age of 62 years. Forty-three carcinomas were pure apocrine carcinoma (PAC; ER−/AR+), and the remaining 21 were classified as apocrine-like carcinomas (ALCs; ER+/−, AR+/−). HER2/neu was positive (score 3+ by IHC and/or amplified by FISH) in 20/43 (47%) PAC and 4/21 (19%) ALC. The prevalence of HER2-low expression (scores 1+ or 2+ without HER2 amplification) in ApoCa was 39% without significant differences between PAC and ALC (P = 0.14); however, the HER2-low phenotype was more prevalent in triple-negative PAC than in ALC (P < 0.001). Levels of TILs were low (≤10%) in 74% of ApoCa (median 5%, range 0%–50%). TIL levels were significantly higher in ALC than in PAC (P = 0.02). HER2 status had no impact on TIL distribution (P = 0.45). The genomic profile of HER2-low ApoCa was similar to other subtypes of ApoCa. ApoCa has predominantly low TIL, particularly PAC. The prevalence of the HER2-low phenotype in ApoCa is high, which should have therapeutic and clinical implications given the recently approved therapies with antibody–drug conjugates (ADCs) for HER2-low breast cancers