Veterinary medicine - Repository of PHD, master's thesis
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Effective Strategies and a Ten-Point Plan for Cardio-Kidney-Metabolic Health in Croatia: An Expert Opinion
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today, we are talking about a new paradigm—cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, an unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies
Abbreviated Breast MRI as a Supplement to Mammography in Family Risk History of Breast Cancer within the Croatian National Breast Screening Program
Objective: To evaluate the diagnostic performance of abbreviated breast MRI compared with mammography in women with a family history of breast cancer included in the Croatian National Breast Screening Program.
Methods: 178 women with a family history of breast cancer aged 50 to 69 underwent abbreviated breast MRI and mammography. Radiological findings for each method were categorized according to the BI-RADS classification. The gold standard for assessing the diagnostic accuracy of breast MRI and mammography, in terms of suspicious BI-RADS 4 and BI-RADS 5 findings, was the histopathological diagnosis. Performance measures, including cancer detection rates, specificity, sensitivity, and positive and negative predictive values, were calculated for both imaging methods.
Results: Twelve new cases of breast cancer were detected, with seven (58.3%) identified only by abbreviated breast MRI, four (33.3%) detected by both mammography and breast MRI, and one (8.3%) diagnosed only by mammography. Diagnostic accuracy parameters for abbreviated breast MRI were 91.67% sensitivity, 94.58% specificity, 55.0% positive predictive value (PPV), and 99.37% negative predictive value (NPV), while for mammography, the corresponding values were 41.67%, 96.39%, 45.46%, and 95.81%, respectively.
Conclusions: Abbreviated breast MRI is a useful supplement to screening mammography in women with a family history of breast cancer. Considering the results of the conducted research, it is recommended to assess whether women with a family history of breast cancer have an increased risk and subsequently provide annual abbreviated breast MRI in addition to mammography for early detection of breast cancer
Functional retinal changes in patients with noninfectious anterior uveitis
Uvod: Iako prednji neinfekcijski uveitis zahvaća strukture prednjeg segmenta oka, zbog disrupcije hemato-okularne barijere moguć je nastanak promjena struktura stražnjeg segmenta oka.
Cilj: Utvrditi postojanje funkcionalnih promjena mrežnice pomoću elektroretinografije kod bolesnika s prednjim neinfekcijskim uveitisom.
Ispitanici i metode: Analizirani su podatci 19 očiju s akutnim prednjim neinfekcijskim uveitisom te kontrolna skupina: zdravo nezahvaćeno oko istog ispitanika koje po svim karakteristikama osim uveitisa odgovara usporedbi sa zahvaćenim okom. Svim ispitanicima učinjen je kompletan oftalmološki pregled, snimane su optička koherentna tomografija (OCT), „full field“ i multifokalna elektroretinografija (ffERG i mfERG). Analizirani su demografski podatci ispitanika, podatci o vidnoj oštrini, kretanju stupnja upale u prednjoj očnoj sobici (POS), biomikroskopskim karakteristikama očiju, promjenama intraokularnog tlaka i fundusa te promjeni parametara OCT-a i ERG-a u periodu praćenja.
Rezultati: Latencije skotopičkih i fotopičkih valova ffERG-a zahvaćenog oka produljene su u akutnom uveitisu te ostaju produljene nakon šest mjeseci. Latencije svih valova mfERG-a značajno su produljene u akutnoj fazi. Amplitude svih valova mfERG-a u akutnom uveitisu više su od amplituda kod zdravog oka.
Zaključak: Kod bolesnika s prednjim neinfekcijskim uveitisom postoje funkcionalne promjene mrežnice dokazive elektroretinografijom.Introduction: Although anterior non-infectious uveitis affects anterior eye segment, due to disruption of the hemato-ocular barrier, changes in the posterior eye segment can occur.
Aim: To determine presence of functional retinal changes in patients with anterior noninfectious uveitis using electroretinography.
Methods: 19 eyes with acute anterior non-infectious uveitis were analyzed, along with control group of healthy unaffected eye of the same subject. It corresponded in all characteristics, except for uveitis, to the comparison with affected eye. All subjects underwent complete ophthalmological examination. Optical coherence tomography (OCT), "full field" and multifocal electroretinography (ff-, mfERG) were recorded. Demographic data of the subjects, data on visual acuity, changes in degree of inflammation in anterior chamber (AC), biomicroscopic characteristics of eyes, changes in intraocular pressure and fundus, changes in OCT and ERG parameters during follow-up period were analyzed.
Results: Latencies of scotopic and photopic ffERG waves of affected eye are prolonged in the acute phase and remain prolonged after six months. Latencies of all mfERG waves are significantly prolonged in the acute phase. Amplitudes of all mfERG waves in acute uveitis are higher than in healthy controls.
Conclusion: Anterior non-infectious uveitis causes functional retinal changes that can be proven by electroretinography
Sustavni pregledi i meta-analiza u medicini: dobri, loši ili zli?
Izlaganje na konferenciji MICC 2024 - (Ne)moguća misija: učinkovito korištenje istraživačkih resurs
Eozinofilni ezofagitis
There has been an extraordinary development in our understanding of eosinophilic esophagitis (EoE) over the last twenty years. This is a chronic immune system disorder that occurs when there is an increase in the numbers of eosinophils in the esophagus, leading to inflammation and symptoms such as chest pain and heartburn and most prominently, dysphagia which refers to food being stuck in the esophagus. It is usually linked to allergies such as food allergies and asthma. The diagnosis normally entails endoscopy and biopsy of the esophageal tissue for diagnosis. The treatment of this disease involves dietary control to avoid allergens, drugs like proton pump inhibitors (PPIs) or topical steroids and occasionally esophageal dilation. Initially, research focused on defining characteristics of the disease and the evaluation of its impact. Recent studies changed this tendency by identifying particular risk factors that could facilitate development of the disease. In this thesis we seek to solidify the current fundamental understandings of this disease, resulting in a comprehensive knowledge base. Furthermore, we present two in depth clinical cases, highlighting how their clinical presentations correlate with the current knowledge base of the disease. Moreover, the paper analyses different modalities of treatments effectiveness as well as implications of untimely therapy.U posljednjih dvadeset godina došlo je do izvanrednog napretka u našem razumijevanju eozinofilnog ezofagitisa (EoE). EoE je kronični poremećaj imunološkog sustava koji se javlja kada se poveća broj eozinofila u jednjaku, što dovodi do upale i simptoma kao što su bol u prsima i žgaravica, a najistaknutiji simptom je disfagija, koja se odnosi na osjećaj zaglavljenosti hrane u jednjaku. EoE je obično povezan s alergijama, poput alergija na hranu i astme. Dijagnoza EoE obično uključuje endoskopiju i biopsiju tkiva jednjaka kako bi se potvrdila prisutnost eozinofila.
Liječenje ove bolesti uključuje kontrolu prehrane kako bi se izbjegli alergeni, lijekove poput inhibitora protonske pumpe ili topičnih steroida te povremeno dilataciju jednjaka. U početku su istraživanja bila usmjerena na definiranje karakteristika bolesti i procjenu njenog utjecaja. Nedavne studije promijenile su taj fokus identificirajući specifične faktore rizika koji bi mogli olakšati razvoj bolesti.
U ovoj tezi nastojimo učvrstiti trenutno temeljno razumijevanje ove bolesti, stvarajući sveobuhvatnu bazu znanja. Nadalje, predstavljamo dva detaljna klinička slučaja, naglašavajući kako njihovi klinički prikazi koreliraju s trenutnim saznanjima o bolesti. Osim toga, rad analizira učinkovitost različitih modaliteta liječenja kao i implikacije nepravovremenog terapijskog pristupa.
Ova teza doprinosi boljem razumijevanju eozinofilnog ezofagitisa, nudeći pregled trenutnog stanja istraživanja, identificirajući ključne faktore rizika i evaluirajući učinkovitost postojećih tretmana
Bolna trigeminalna neuropatija
Painful trigeminal neuropathy is a potentially debilitating yet not well known neurological disease. Its hallmarks are specific sensory abnormalities and persistent facial pain. This review consolidates current knowledge on its symptoms, underlying causes, diagnostic challenges including the differential diagnosis, and treatment options linked to this condition.
The pathognomonic symptoms of painful trigeminal neuropathy help in correctly diagnosing this condition. These include sensory disturbances of painful trigeminal neuropathy, such as hypoesthesia, hyperesthesia, itching symptoms, taste alterations as well as motor function disturbance of the jaw. Depending on which specific branches of the trigeminal nerve are involved in each patient, the symptoms can differ accordingly. Therefore, understanding of the distribution and nature of the symptoms of painful trigeminal neuropathy is crucial for diagnosis.
The pathophysiology is influenced by a broad range of etiological events, including infections, trauma, systemic illnesses, and surgical procedures. To distinguish painful trigeminal neuropathy from other illnesses causing facial pain, such as trigeminal neuralgia, a comprehensive clinical evaluation and imaging procedures, including magnetic resonance imaging, are necessary for the diagnosis process. Painful trigeminal neuropathy is treated individually with a range of approaches, from minimally invasive and medicinal therapy to more involved forms of care.Bolna trigeminalna neuropatija je potencijalno iscrpljujuća, ali nedovoljno poznata neurološka bolest. Njegova obilježja su specifične senzorne abnormalnosti i stalna bol lica. Ovaj pregled konsolidira trenutno znanje o njegovim simptomima, temeljnim uzrocima, dijagnostičkim izazovima uključujući diferencijalnu dijagnozu i mogućnostima liječenja povezanima s ovim stanjem.
Patognomonični simptomi bolne trigeminalne neuropatije pomažu u ispravnom dijagnosticiranju ovog stanja. To uključuje senzorne poremećaje bolne trigeminalne neuropatije, kao što su hipoestezija, hiperestezija, simptomi svrbeža, promjene
okusa kao i poremećaj motoričke funkcije čeljusti. Ovisno o tome koje su specifične grane trigeminalnog živca uključene u svakog pacijenta, simptomi se mogu razlikovati u skladu s tim. Stoga je razumijevanje distribucije i prirode simptoma bolne trigeminalne neuropatije ključno za dijagnozu.
Na patofiziologiju utječe širok raspon etioloških događaja, uključujući infekcije, traume, sistemske bolesti i kirurške zahvate. Kako bi se bolna neuropatija trigeminusa razlikovala od drugih bolesti koje uzrokuju bol u licu, kao što je neuralgija trigeminusa, potrebna je sveobuhvatna klinička procjena i postupci snimanja, uključujući magnetsku rezonanciju, za proces dijagnoze. Bolna trigeminalna neuropatija liječi se individualno nizom pristupa, od minimalno invazivne i medikamentozne terapije do složenijih oblika skrbi
Vrste parcijalnih endoproteza koljena
The knee joint, comprising four bones, and three compartments -medial tibiofemoral, lateral tibiofemoral, and patellofemoral. Ligaments, such as the ACL and PCL, enhance the stability. Knee osteoarthritis, characterized by cartilage degeneration and osteophyte formation is one of the most prevalent causes of disability. There are many risk factors – modifiable and nonmodifiable. Diagnosis based history, examination, and imaging. Treatment options range from conservative treatment to knee arthroplasty and surgeries depend on the clinical symptoms and disease progression.
Unicompartmental knee arthroplasty is indicated for cartilage degeneration limited to single compartment. Criteria include stable joints and correctable deformities. For certain patients unicompartmental knee arthroplasty shows advantages over total knee arthroplasty.
Among the various types of implants available for unicompartmetal knee arthroplasty, fixed bearing implants provide stability and simplicity, reducing the risk of dislocation and surgical complications. However, they may limit their range of motion. compared to their mobile-bearing counterparts. On the other hand, mobile bearing implants allow for more natural movement and range of motion, minimizing polyethylene wear and stress on the bone-implant interface. Those implants have a higher risk of dislocation.
Another consideration in implant selection is the design, whether single radius or dual radius. Single radius implants provide consistent motion and stability, while dual radius implants offer enhanced flexibility and range of motion. Patient activity level plays an important factor in determining suitable design.
Furthermore, all polyethylene components offer simplicity and cost-effectiveness, with potential for bone preservation, but they may experience greater wear and fixation issues. Metal-backed components, on the other hand, provide durability, stability, and flexibility, but they may pose challenges during revision surgeries and carry a risk of metal ion release.Jedan od najčešćih uzroka invaliditeta današnjice je osteoartritis koljena, bolest koja se očituje u degeneraciji hrskavice i stvaranju osteofita. Za nju postoje mnogi promjenjivi i nepromjenjivi čimbenici rizika. Dijagnoza se temelji na anamnezi, pregledu i slikama, a liječenje se može provoditi u rasponu od konzervativnog do artroplastike koljena. Operativne mogućnosti ovise o kliničkim simptomima i progresiji bolesti.
Glavni je cilj ovoga rada predstaviti složenu anatomiju zgloba koljena i pružiti sveobuhvatne podatke o indikacijama i etiologijama za unikompartmentalne zamjenu koljena. Istraživanje uspoređuje različite vrste unikompartmentalne implantata za koljeno te prikazuje rezultate i rehabilitaciju nakon unikompartmentalne zamjene koljena, ističući razlike u odnosu na totalnu artroplastiku koljena. Usporedbom se nastoji pružiti vrijedne uvide u najbolji izbor implantata i očekivane ishode unikompartmentalne zamjene koljena.
Unikompartmentalne artroplastika koljena indicirana je za degeneraciju hrskavice ograničenu na jedan odjeljak, a preduvjet su stabilni zglobovi i ispravljive deformacije. Kod nekih je pacijenata pokazala prednosti u odnosu na artroplastiku cijelog koljena. Postoje različite vrste implantata, primjerice implantati s fiksnim ležajem pružaju stabilnost i jednostavnost, smanjujući rizik od dislokacije i kirurških komplikacija. Međutim, mogu ograničiti kretanje. Mobilni nosivi implantati, pak, omogućuju prirodnije kretanje i raspon pokreta, smanjujući trošenje polietilena te trenje na spoju kosti i implantata, no imaju veći rizik od dislokacije. Pri odabiru implantata u obzir treba uzeti i dizajn: implantati s jednostrukim radijusom pružaju dosljedno kretanje i stabilnost dok implantati s dvostrukim radijusom nude poboljšanu fleksibilnost i raspon pokreta. Najvažniji čimbenik u određivanju prikladnog dizajna je razina tjelesne aktivnosti pacijenta.
Nadalje, polietilenske komponente osiguravaju jednostavnost i ekonomičnost te mogućnost očuvanja kosti, ali mogu pokazivati veće znakove trošenja i imati poteškoća s učvršćivanjem, dok metalne komponente pružaju izdržljivost, stabilnost i fleksibilnost, ali mogu uzrokovati komplikacije tijekom revizijskih operacija i nose rizik od oslobađanja metalnih iona
Association of anti-diabetic drugs and covid-19 outcomes in patients with diabetes mellitus type 2 and chronic kidney disease: Nationwide registry analysis
Introduction: Patients with diabetes mellitus type 2 and chronic kidney disease (T2DM-CKD) have a 5 times higher risk of developing severe SARS-CoV-2 infection than those without these 2 diseases. The goal of this study is to provide information on T2DM-CKD and COVID-19 outcomes, with an emphasis on the association with anti-diabetic medications.
Methodology: Study is designed as a retrospective cohort analysis covering the years 2020 and 2021. Data from the National Diabetes Registry (CroDiab) were linked to hospital data, primary healthcare data, Causes of Death Registry data, the SARS-CoV-2 vaccination database, and the SARS-CoV-2 test results database. Study outcomes were cumulative incidence of SARS-CoV-2 positivity, COVID-19 hospitalizations, and COVID-19 deaths. For outcome predictors, logistic regression models were developed.
Results: Of 231 796 patients with diabetes mellitus type 2 in the database, 7 539 were T2DM-CKD (3.25%). The 2-year cumulative incidences of all three studies' outcomes were higher in T2DM-CKD than in diabetes patients without CKD (positivity 18.1% vs. 14.4%; hospitalization 9.7% vs. 4.2%; death 3.3% vs. 1.1%, all p<0.001). For COVID-19 hospitalization, protective factors were SGLT-2 inhibitors use (OR 0.430; 95%CI 0.257-0.719) and metformin use (OR 0.769; 95% CI 0.643-0.920), risk factors were insulin use (1.411; 95%CI 1.167-1.706) and sulfonylureas use (OR 1.226; 95% CI 1.027-1.464). For SARS-CoV-2 positivity protective factors were SGLT-2 inhibitors (0.607; 95% CI 0.448-0.823), repaglinide use (OR 0.765; 95% CI 0.593-0.986) and metformin use (OR 0.857; 95% CI 0.770-0.994). DPP-4 inhibitors showed a non-significant decrease in risk for COVID-19 death (OR 0.761; 95% CI 0.568-1.019).
Conclusion: T2DM-CKD are heavily burdened by COVID-19 disease. Our results suggest no association between antidiabetic drugs and COVID-19 death outcome while SGLT-2 and metformin show to be protective against COVID-19 hospitalization and infection, repaglinide against infection, and insulin and sulfonylureas show to be risk factors for COVID-19 hospitalization and infection. Further research in T2DM-CKD is needed
Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC)
Squamous cell lung carcinoma (SqCLC) is associated with high mortality and limited treatment options. Identification of therapeutic targets and prognostic biomarkers is still lacking. This research aims to analyze the transcriptomic profile of SqCLC samples and identify the key genes associated with tumorigenesis, overall survival (OS), and a profile of the tumor-infiltrating immune cells. Differential gene expression analysis, pathway enrichment analysis, and Gene Ontology analysis on RNA-seq data obtained from FFPE tumor samples (N = 23) and healthy tissues (N = 3) were performed (experimental cohort). Validation of the results was conducted on publicly available gene expression data using TCGA LUSC (N = 225) and GTEx healthy donors’ cohorts (N = 288). We identified 1133 upregulated and 644 downregulated genes, common for both cohorts. The most prominent upregulated genes were involved in cell cycle and proliferation regulation pathways (MAGEA9B, MAGED4, KRT, MMT11/13), while downregulated genes predominately belonged to immune-related pathways (DEFA1B, DEFA1, DEFA3). Results of the survival analysis, conducted on the validation cohort and commonly deregulated genes, indicated that overexpression of HOXC4 (p < 0.001), LLGL1 (p = 0.0015), and SLC4A3 (p = 0.0034) is associated with worse OS in early-stage SqCLC patients. In contrast, overexpression of GSTZ1 (p = 0.0029) and LILRA5 (p = 0.0086) was protective, i.e., associated with better OS. By applying a single-sample gene-set enrichment analysis (ssGSEA), we identified four distinct immune subtypes. Immune cell distribution suggests that the memory T cells (central and effector) and follicular helper T cells could serve as important stratification parameters
S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology
Introduction: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies.
Methods: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings.
Results: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD.
Conclusion: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD