Veterinary medicine - Repository of PHD, master's thesis
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Surgery treatment options in high grade rigid scoliosis
No full textOvaj diplomski rad usmjeren je na operacijsko zbrinjavanje teških rigidnih skolioza, kompleksnih deformacija kralježnice, koje se najčešće definiraju glavnom krivinom većom od 80°, te malom fleksibilnosti izmjerenoj na korigiranim snimkama. Rigidna deformacija se slikana u maksimalnoj korekciji korigira manje od 25%. U radu se obrađuju osnovna definicija skolioze, klasifikacija skolioza, te prikazuje klinička slika i dijagnostički algoritam koji uključuje uzimanje anamneze, klinički pregled i radiološku dijagnostiku- rendgen, magnetsku rezonancu, CT i moderne metode poput 3D ultrazvuka i površinske topografije. Poseban naglasak stavljen je na mogućnost operacijskog zbrinjavanja teških rigidnih skolioza. Kod bolesnika s rigidnim deformacijama, liječenje podrazumijeva multidisciplinarni pristup. Liječenje najčešće uključuje kombinaciju postupaka, poput halo-trakcije, te različitih kirurških tehnika. Halo-trakcija može se koristiti perioperativno, intraoperativno ili između kirurških zahvata. Kroz rad prikazane su suvremene operacijske metode koje uključuju posteriornu spinalnu dekompresiju, razne vrste osteotomija, prednju spinalnu dekompresiju, kao i zahtjevnije zahvate poput stražnje vertebralne resekcije (PVCR) i vertebralne dekancelacije (PVCD). Operativni pristup odabire se individualno, uzimajući u obzir više faktora, kao što su težina i fleksibilnost deformiteta, dob pacijenta te rizik od komplikacija. Na kraju, rad ističe važnost sveobuhvatnog pristupa i preciznog planiranja liječenja, timske suradnje različitih specijalista s ciljem što sigurnije i učinkovitije korekcije skolioze, uz smanjenje rizika od komplikacija i poboljšanje ukupne kvalitete života bolesnika.This graduate thesis focuses on the surgical management of severe rigid scoliosis—complex spinal deformities that remain a challenge despite advances in diagnostics and therapy. Such deformities are most commonly defined as a major curve greater than 80 degrees, with significantly reduced flexibility measured on bending x-ray. Rigid is an in bending correction less than 25%. The introductory chapters of the thesis present the basic definitions and classification of scoliosis, followed by a description of the clinical presentation and a detailed diagnostic algorithm that includes medical history, clinical examination, and imaging studies—X-ray, magnetic resonance imaging, computed tomography, and modern methods such as 3D ultrasound and surface topography. Special emphasis is placed on the possibilities of surgical treatment for severe and rigid spinal deformities. Since these deformities are often associated with an increased risk of complications, reduced pulmonary function, and potential neurological deficits, treatment requires a multidisciplinary approach. Typically, a combination of halo traction and surgical techniques is used. Halo traction plays an important role and can be applied perioperatively, intraoperatively, or between staged surgeries, with the aim of increasing spinal flexibility and reducing surgical risk. The thesis describes modern surgical techniques used in the treatment of rigid scoliosis, including posterior spinal decompression, various types of osteotomies, anterior spinal decompression, as well as more complex procedures such as posterior vertebral column resection (PVCR) and vertebral column decancellation (PVCD). The choice of surgical approach is individualized, taking into account multiple factors such as the severity and flexibility of the deformity, the patient’s age, and the risk of complications. Finally, the paper emphasizes the importance of a comprehensive approach and precise treatment planning, as well as the collaboration of various medical specialists, in order to ensure the safest and most effective scoliosis correction with reduced risk of complications and improved overall quality of life
Targeted therapy in metastatic melanoma
No full textMelanom je prema učestalosti među rjeđim, a po malignosti jedan od najagresivnijih tumora
kože. Iako je uzrok nastanka melanoma kože multifaktorijalan, najvažnijim etiološkim
čimbenikom u razvoju bolesti smatra se izloženost UV zračenju. U razvijenim državama došlo
je do velikog porasta u incidenciji melanoma, zbog čega su pokrenute mnoge
javnozdravstvene kampanje prevencije i ranog otkrivanja, obzirom da je ključni čimbenik za
smanjenje mortaliteta upravo rano otkrivanje. Melanom se klinički prezentira kao pigmentirana
lezija koja se vremenom mijenja te se dijagnosticira kliničkim pregledom ili dermatoskopijom.
Svaku sumnjivu leziju potrebno je kirurški odstraniti te poslati na patohistološku analizu. Nakon
što se potvrdi dijagnoza melanoma, potrebno je odrediti stadij bolesti koristeći TNM
klasifikaciju koja kategorizira obilježja primarnog tumora (T), zahvaćenost limfnih čvorova (N)
i prisutnost udaljenih metastaza (M). Prema TNM klasifikaciji tumore dijelimo u stadije pri čemu
je stadij 0 tumor in situ, stadij I i II podrazumijevaju lokaliziranu bolest, stadij III bolest koja
zahvaća regionalne limfne čvorove, a stadij IV postojanje udaljenih metastaza. Ovisno o
samom stadiju, određuje se liječenje. Prognoza bolesti je lošija što je viši stadij. Napretkom
medicine došlo je do razvitka novih terapijskih opcija, imunoterapije (inhibitora kontrolnih
točaka imunološkog sustava) i ciljane terapije (BRAF i MEK inhibitora). Nove terapijske opcije
rezultirale su boljim preživljenjem pacijenata, posebice u kasnijim stadijima bolesti.Melanoma is one of the rarest skin tumors in terms of frequency and one of the most
aggressive in terms of malignancy. Although the cause of skin melanoma is multifactorial,
exposure to UV radiation is considered to be the most important etiological factor in the
development of the disease. In developed countries, there has been a significant increase in
the incidence of melanoma, which is why many public health campaigns for prevention and
early detection have been launched, since early detection is the key factor in reducing
mortality. Melanoma is clinically presented as a pigmented lesion that changes over time and
is diagnosed by clinical examination or dermatoscopy. Any suspicious lesion should be
surgically removed and sent for pathohistological analysis. Once the diagnosis of melanoma
is confirmed, it is necessary to determine the stage of the disease using the TNM classification,
which categorizes the characteristics of the primary tumor (T), lymph node involvement (N)
and the presence of distant metastases (M). According to the TNM classification, tumors are
divided into stages, with stage 0 being a tumor in situ, stages I and II implying localized disease,
stage III disease affecting regional lymph nodes, and stage IV the presence of distant
metastases. Treatment is determined depending on the stage itself. The prognosis of the
disease is worse the higher the stage. Advances in medicine have led to the development of
new therapeutic options, immunotherapy (immune system checkpoint inhibitors) and targeted
therapy (BRAF and MEK inhibitors). New therapeutic options have resulted in better patient
survival, especially in the later stages of the disease
Integrating artificial intelligence in clinical pharmacology: Opportunities, challenges and ethical imperatives
No full textOvaj rad opisuje transformacijski potencijal umjetne inteligencije (AI) u području kliničke farmakologije, s naglaskom na mogućnosti, izazove i etičke implikacije njezine integracije. AI tehnologije, uključujući strojno učenje (ML), duboko učenje (DL) i strojnu obradu jezika (NLP), značajno mijenjaju način otkrivanja lijekova, optimizacije kliničkih ispitivanja te personalizacije terapije. Prikazani su primjeri uspješne primjene AI u identifikaciji novih terapijskih ciljeva, prenamjeni indikacije lijekova, dizajnu nanonosača i optimizaciji kliničkih protokola. Također se razmatraju izazovi poput ograničene mogućnosti generalizacije rezultata, netransparentnih algoritama, rizika od algoritamske pristranosti te problema privatnosti podataka. Autori upozoravaju na etičke prijetnje, uključujući mogućnost zlouporabe AI za razvoj biološkog oružja, i naglašavaju potrebu za čvrstim regulatornim okvirom i edukacijom
zdravstvenih djelatnika o odgovornoj primjeni AI. Zaključno, AI ima potencijal značajno unaprijediti kliničku farmakologiju, no za njezinu sigurnu i učinkovitu integraciju potrebni su multidisciplinarna suradnja, transparentnost i kontinuirana evaluacija njezine primjene u kliničkoj praksi.The transformative potential of artificial intelligence (AI) in the field of clinical pharmacology is explored, with a focus on its opportunities, challenges, and ethical implications. AI technologies, including machine learning (ML), deep learning (DL), and natural language processing (NLP), are significantly reshaping drug discovery, clinical trial optimization, and personalized therapy. Examples of successful AI applications are presented, such as the identification of novel therapeutic targets, drug repurposing, nanocarrier design, and the optimization of clinical protocols. The discussion also addresses challenges such as limited generalizability of results, algorithmic opacity, risks of algorithmic bias, and data privacy concerns. The authors highlight ethical threats, including the potential misuse of AI in the development of biological weapons, and emphasize the need for a robust regulatory framework and the education of healthcare professionals on the responsible use of AI. In conclusion, while
AI holds significant promise for advancing clinical pharmacology, its safe and effective integration requires multidisciplinary collaboration, transparency, and continuous evaluation of its application in clinical practice
The influence of meteorological conditions on the rupture of membranes in term pregnancies
No full textPrijevremeno prsnuće plodovih ovoja (RVP) označava pucanje vodenjaka najmanje 2 sata prije početka trudova. Preterminski RVP (PRVP) javlja se prije 37. tjedna trudnoće. RVP može uzrokovati komplikacije poput infekcija i abrupcije posteljice. Uzroci uključuju mehaničko opterećenje, infekcije, upalu, oksidativni stres i genetske faktore. Dijagnosticira se kliničkim pregledom i biokemijski, a u terminu liječi indukcijom porođaja. Meteorološki čimbenici, poput promjene tlaka i temperature, potencijalno mogu utjecati na početak porođaja i pucanje ovoja. Provedeno je retrospektivno istraživanje u Klinici za ženske bolesti i porode KBC-a Zagreb tijekom 2024. godine. Analizirano je 2913 porođaja, s usporedbom trudnica s i bez RVP-a, uz detaljnu analizu porođaja u terminu. Meteorološke podatke ustupio je Državni hidrometeorološki zavod za postaju Maksimir. Razina statističke značajnosti postavljena je na α=0,05. Od 2913 porođaja, 2582 (88,6 %) je bilo terminskih, a 331 (11,4 %) prijevremenih. RVP je zabilježen u 389 trudnica (13,4 %), češće u prijevremenim (28,4 %) nego u terminskim porođajima (11,4 %) (p < 0,001). Trudnice s RVP-om imale su manje trudnoća (1,98 vs. 2,36) i porođaja (1,65 vs. 1,99), kraću trudnoću (274,1 vs. 276,8 dana)(p < 0,001) te manju novorođenačku masu (3374 g vs. 3474 g; p = 0,002). Nije bilo razlika u duljini novorođenčadi ni u zbroju po Apgarovoj. Kod RVP-a zabilježen je niži tlak (1000,75 vs. 1001,82 hPa; p = 0,035) i viša temperatura zraka (14,88 °C vs. 13,54 °C; p = 0,014), no ROC analiza nije potvrdila dovoljnu osjetljivost ni specifičnost za predikciju RVP-a. Učestalost RVP-a nije se značajno razlikovala između dana s tlakom ispod (12,1 %) i iznad prosjeka (10,5 %) (p = 0,189). Uočena je statistička povezanost nižeg tlaka i više temperature zraka s RVP-om, ali bez kliničke prediktivne vrijednosti.Preterm rupture of membranes (PROM) is the rupture of fetal membranes at least 2 hours before the onset of labor. Preterm PROM (PPROM) occurs before 37 weeks of gestation. PROM can cause complications like infections and placental abruption, and is linked to factors such as mechanical stress, infection, inflammation, oxidative stress, and genetics. Diagnosis is made through clinical examination and biochemical tests, and managed by labor induction at term. Meteorological factors, particularly air pressure and temperature, may influence the onset of labor and membrane rupture. A retrospective study was conducted in 2024 at the University Hospital Centre Zagreb, analyzing 2,913 deliveries to compare women with and without PROM, with a detailed analysis of term births. The Croatian Meteorological and Hydrological Service provided meteorological data for the Maksimir station. The statistical significance was set at α = 0.05. Of 2,913 deliveries, 2,582 (88.6 %) were term and 331 (11.4 %) preterm. PROM occurred in 389 women (13.4 %), more frequently in preterm (28.4 %) than in term deliveries (11.4 %) (p < 0.001). Women with PROM had fewer pregnancies (1.98 vs. 2.36) and deliveries (1.65 vs. 1.99), shorter gestation (274.1 vs. 276.8 days) (p < 0.001), and lower birth weight (3374 g vs. 3474 g; p = 0.002). There were no differences in neonatal length or Apgar scores. PROM cases were associated with lower air pressure (1000.75 vs. 1001.82 hPa; p = 0.035) and higher temperature (14.88 °C vs. 13.54 °C; p = 0.014), but ROC analysis did not show sufficient sensitivity or specificity to predict PROM. PROM rates did not differ significantly between days with below- (12.1%) and above-average air pressure (10.5%) (p = 0.189). A statistically significant association was observed between lower air pressure and higher temperature with PROM, but without clinical predictive value
Monoclonal gammopathies of clinical significance
No full textMonoklonske gamapatije predstavljaju skupinu poremećaja obilježenu proliferacijom klonskih plazma stanica koje luče M-protein. Prisutnost M-proteina u serumu bez kriterija za druge plazmastanične proliferativne bolesti označava monoklonsku gamapatiju neodređenog značenja (MGUS). Ranije se nazivala i „benigna monoklonska gamapatija“, no to je pogrešan naziv, jer MGUS može progredirati u plazmastaničnu proliferativnu bolest poput multiplog mijeloma. Osim toga pokazalo se da M-protein uzrokuje ciljana oštećenja organa bez razvoja maligne bolesti, uključujući nefropatije, neuropatije i dermatopatije. Monoklonska gamapatija bubrežnog značenja (MGRS) je pojam koji je Međunarodna skupina za istraživanje bubrega i monoklonske gamapatije uvela 2012. godine te predstavlja bubrežna oštećenja povezana s M-proteinom. Bubrežne lezije mogu biti posljedica taloženja monoklonskih proteina, imunoloških mehanizama te vaskularnih lezija. Klinička prezentacija MGRS-a je vrlo široka i ovisi o tome koji je dio nefrona zahvaćen. Može biti glomerulopatija, tubulopatija ili vaskularna zahvaćenost s heterogenom kliničkom prezentacijom. Dijagnostika MGRS-a uključuje hematološku obradu, poput elektroforeze proteina u serumu i urinu, analizu slobodnih lakih lanaca, biopsiju koštane srži, a za točnu klasifikaciju i histopatološku analizu bubrežne lezije je potrebna biopsija bubrega te izgled naslaga na elektronskoj mikroskopiji. Monoklonska gamapatija od kožnog značenja predstavlja stanja u kojima zbog M-proteina dolazi do kožnih manifestacija, najčešće zbog taloženja monoklonskih imunoglobulina i djelovanja citokina. Klinička prezentacija je široka i ovisi o bolesti koja je povezana s M-proteinom. Neuropatija je češće perifernog oblika te je progresivna bolest. Terapija monoklonskih gamapatija sa sistemskih manifestacijama se temelji na eliminaciji klona koji luči toksični M-protein. Rano prepoznavanje monoklonskih gamapatija sa sistemskim manifestacijama je vrlo bitno kako bi se liječenje započelo što ranije i kako bi se spriječile ireverzibilne promjene organa i smanjio morbiditet pacijenata.Monoclonal gammopathies represent a group of disorders characterized by the proliferation of clonal plasma cells that secrete M-protein. The presence of M-protein in the serum without fulfilling the criteria for other plasma cell proliferative diseases is defined as monoclonal gammopathy of undetermined significance (MGUS). It was previously referred to as "benign monoclonal gammopathy," but this term is misleading because MGUS can progress to a plasma cell proliferative disease such as multiple myeloma, in addition, it has been shown that M-protein can cause targeted organ damage without malignant transformation. These organ damages include nephropathies, neuropathies, and dermatopathies. Monoclonal gammopathy of renal significance (MGRS) is a term introduced by the International Kidney and Monoclonal Gammopathy Research Group in 2012 and refers to kidney damage caused by M-protein. Renal lesions may result from the deposition of monoclonal proteins, immune-mediated mechanisms, or vascular injury. The clinical presentation of MGRS is broad and depends on which part of the nephron is affected. It may manifest as glomerulopathy, tubulopathy, or vascular involvement, each with heterogeneous clinical features. The diagnosis of MGRS involves hematological workup, including serum and urine protein electrophoresis, free light chain analysis, and bone marrow biopsy. For accurate classification and histopathological assessment of renal lesions, a kidney biopsy and evaluation of deposit morphology via electron microscopy are required. Monoclonal gammopathy of cutaneous significance refers to conditions in which M-protein leads to cutaneous manifestations, most commonly due to the deposition of monoclonal immunoglobulins and cytokine activity. The clinical presentation is variable and depends on the associated M-protein–related disease. Neuropathy associated with monoclonal gammopathies is more commonly peripheral and is typically a progressive condition. The treatment of monoclonal gammopathies with systemic manifestations is based on the elimination of the clonal population that secretes the pathogenic M-protein. Early recognition of monoclonal gammopathies with systemic involvement is crucial to enable timely initiation of therapy, prevent irreversible organ damage, and reduce patient morbidity
Treatment of patients with ovarian cancer after neoadjuvant chemotherapy
No full textZbog nedostatka dovoljno pouzdanih probirnih metoda i učestalog postavljanja dijagnoze u kasnom stadiju, karcinom jajnika predstavlja veliki dijagnostički izazov. Simptomi bolesti često su nespecifični – bolesnice često pripisuju simptome stresu, promjenama u prehrani ili poremećajima peristaltike, što u većini slučajeva rezultira postavljanjem dijagnoze u uznapredovalom stadiju bolesti, najčešće stadiju III ili IV.
Povijesno gledano, primarna citoredukcija (PDS, engl. primary debulking surgery) je bio temelj liječenja karcinoma jajnika, s ciljem maksimalnog smanjenja tumorske mase prije početka kemoterapije. Citoredukcija ima osim terapijske i dijagnostičku vrijednost jer omogućuje procjenu opsega proširenosti bolesti i mogućnosti potpune resekcije. Optimalna citoredukcija, definirana kao rezidualna bolest karcinoma jajnika jednaka ili manja od 1 cm, je najvažniji prognostički čimbenik. Manji rezidualni tumori ili kompletna citoredukcija povezani su s duljim preživljenjem i boljim terapijskim ishodom.
Sve više studija danas zagovara primjenu neoadjuvantne kemoterapije (NACT, engl. Neoadjuvant chemotherapy) kao terapijsku opciju kod bolesnica koje zbog lošeg općeg stanja, opsežne tumorske mase ili komorbiditeta nevezanih uz bolest nisu kandidati za primarni kirurški zahvat. Uvođenje NACT u takvih bolesnica je poboljšalo stopu optimalne citoredukcije i smanjilo učestalost postoperativnih komplikacija te ujedno poboljšao prognozu i preživljenje. Odluka između PDS i NACT mora biti individualizirana, uzimajući u obzir biologiju tumora, funkcionalni status i komorbiditete bolesnice i mogućnost optimalne resekcije.Because of a lack of effective screening methods and diagnosis often in advanced stages, ovarian cancer is a diagnostic challenge. Symptoms are often unspecific –usually written off to stress, dietary changes or digestive disturbances. That results in diagnosis in stages III or IV.
Historically speaking, primary debulking surgery (PDS) was the foundation of ovarian cancer treatment, aiming for maximal tumor resection before chemotherapy. Cytoreduction has not only a therapeutic value, but also a diagnostic one, for it assesses the likelihood of achieving a complete resection. Optimal cytoreduction, defined as residual disease equal to or less than one centimeter, is the most important prognostic factor. A complete resection or smaller residual tumors are connected with prolonged survival and better outcome.
More and more studies advocate for neoadjuvant chemotherapy (NACT) as an alternative approach for patients with low performance status, large tumor masses and comorbidities that enable them to receive PDS. The emergence of NACT has enhanced the ability to achieve optimal cytoreduction and has reduced the rate of postoperative complications It has also improved overall survival and outcomes in those patients, which proves it´s noninferiority to PDS. The choice between the two approaches must be made on an individual level, taking tumor biology, patient´s performance status and comorbidities into account, while also assessing the possibility of optimal cytoreduction
Upper gastrointestinal tumor bleeding
No full textKrvareći tumori gornjeg dijela gastrointestinalnog sustava odnose se na krvarenje koje potječe iz neoplazimi smještenih u gornjem dijelu probavnog trakta, uključujući jednjak, želudac i dvanaesnik. Makar je rijeđe u usporedbi s peptičkom ulkusnom bolest, ezofagitisom, gastroduodenitisom, varikozitetima ili erozivnim gastritisom, tumorozno krvarenje nosi veći klinički značaj jer se često javlja u kasnim stadijima bolesti, uz visoke stope ponovnog krvarenja i hemostatsku nestabilnost pacijenata. Incidencija krvarenja iz tumora gornjeg GI čini oko 5% svih slučajeva gornjeg gastrointestinalnog krvarenja(UGIB). Dijagnoza se temelji na kliničkoj anamnezi, fizikalnom pregledu i laboratorijskim nalazima. Pacijenti se često javljaju s hematemezom (povraćanje svježe krvi), melenom (crna, katranasta stolica) ili hematokezijom ( svježa krv u stolici). Prognostički sustavi bodovanja kao što su Glasgow- Blatchford, Rockall i AIMS65 koriste se za stratifikaciju pacijenata na temelju težine krvarenja i pomažu kod donošenja terapijskih odluka. Ako je potrebno, početno zbrinjavanje započinje hemodinamskom stabilizacijom, nadoknadu tekućine intravenskim putem, transfuzije krvi prema potrebi i davanjem inhibitora protonske pumpe. Nakon toga pristupa se endoskopiji (EGD). Ona predstavlja zlatni standard u dijagnostici jer omogućava direktnu vizualizaciju krvareće lezije, hemostazu i uzimanje biopsije. Endoskopsko liječenje uključuje injekcijsku terapiju s epinefrinom, mehaničko zaustavljanje krvarenja pomoću klipsi i termalne metode. Kod difuznog tumorskog krvarenja primjenom hemostatskog prahova poput TC-325 (Hemospray), postiže se visoka stopa neposredne hemostaze. Računalna tomografija s angiografijom (CTA) i kateterska angiografija koriste se kod pacijenata s perzistentnim ili jakim krvarenjem kada je endoskopija neuspješna. CTA omogućuje brzo i neinvazivno otkrivanje aktivnog krvarenja, dok angiografija pruža mogućnost terapijske embolizacije. U slučajevima površinskih neoplazmi koristi se endoskopska mukozna resekcija (EMR) ili submukozna disekcija (ESD), uz povećan rizik od krvarenja koji se može umanjiti primjenom lokalnih hemostatskih sredstava. Kada endoskopski zahvati ne uspiju ili su tehnički neizvedivi, slijedi intervencijska radiologija s embolizacijom ili, rjeđe, kirurški zahvati. Liječenje zahtijeva multidisciplinarni pristup koji uključuje gastroenterologe, radiologe, kirurge i onkologe. Tumorsko krvarenje često je znak uznapredovale bolesti, pa je važno razmotriti i palijativne pristupe, poput radioterapije, s ciljem poboljšanja kvalitete života pacijenata.Bleeding tumors of the upper gastrointestinal (GI) tract refer to hemorrhage originating from neoplasms located in the upper part of the digestive tract, including the esophagus, stomach, and duodenum. Although less common compared to peptic ulcer disease, esophagitis, gastroduodenitis, varices, or erosive gastritis, tumor-related bleeding carries greater clinical significance because it often occurs in the later stages of the disease, with high rates of rebleeding and hemostatic instability in patients. The incidence of bleeding from upper GI tumors accounts for about 5% of all cases of upper gastrointestinal bleeding. Diagnosis is based on clinical history, physical examination, and laboratory findings. Patients often present with hematemesis (vomiting fresh blood), melena (black, tarry stool), or hematochezia (fresh blood in the stool). Prognostic scoring systems such as the Glasgow-Blatchford, Rockall, and AIMS65 scores are used to stratify patients based on the severity of bleeding and assist in making therapeutic decisions. Initial management, when necessary, begins with hemodynamic stabilization, intravenous fluid replacement, blood transfusions as needed, and administration of proton pump inhibitors. This is followed by endoscopy (EGD), which represents the gold standard in diagnosis, as it allows for direct visualization of the bleeding lesion, hemostasis, and biopsy sampling. Endoscopic treatment includes injection therapy with epinephrine, mechanical hemostasis using clips, and thermal methods. In cases of diffuse tumor bleeding, the use of hemostatic powders such as TC-325 (Hemospray) achieves a high rate of immediate hemostasis. Computed tomography with angiography (CTA) and catheter angiography are used in patients with persistent or massive bleeding when endoscopy is unsuccessful. CTA provides a rapid and non-invasive method for detecting active bleeding, while angiography offers the possibility of therapeutic embolization. In cases of superficial neoplasms, endoscopic mucosal resection (EMR) or submucosal dissection (ESD) is used, with an increased risk of bleeding that can be mitigated by the application of local hemostatic agents. When endoscopic procedures fail or are technically unfeasible, interventional radiology with embolization is considered, or more rarely, surgical intervention. Treatment requires a multidisciplinary approach involving gastroenterologists, radiologists, surgeons, and oncologists. Tumor-related bleeding is often a sign of advanced disease, so it is also important to consider palliative approaches such as radiotherapy, with the aim of improving the patient's quality of life
Diagnostic and epidemiological landscape of anaerobic bacteria in Europe, 2020–2023 (ANAEuROBE)
No full textIntroduction: Despite being implicated in a wide spectrum of community- and healthcare-acquired infections, anaerobes have not yet been incorporated into systematic surveillance programs in Europe.
Methods: We conducted a multicentre retrospective observational study analysing all anaerobic strains isolated from blood cultures in 44 European Hospital Centres over a 4-y period (2020-2023). Diagnostic approach, epidemiology, and antimicrobial susceptibility according to EUCAST v. 15.0 were investigated.
Results: Our study included 14,527 anaerobes, most of which were Gram-positive (45%) or Gram-negative (40%) bacilli. MALDI-TOF coupled to mass spectrometry was the most widely used tool for species identification (98%). Antimicrobial susceptibility testing was performed in the vast majority of centres, using mostly gradient diffusion strip (77%) and disk diffusion (45%) methods according to EUCAST guidelines. The most prevalent species were Cutibacterium acnes (18.7%), Bacteroides fragilis (16.3%), Clostridium perfringens (5.3%), Bacteroides thetaiotaomicron (4.2%), Fusobacterium nucleatum (3.5%), and Parvimonas micra (3.4%). C. acnes showed high resistance to benzylpenicillin (18%), clindamycin (39%), and imipenem (19% and 13% by MIC methods and disk diffusion, respectively). B. fragilis showed high resistance to amoxicillin/clavulanate (24%), piperacillin/tazobactam (22% and 14% by MIC methods and disk diffusion, respectively), clindamycin (22% by both MIC methods and disk diffusion), meropenem (13%), and metronidazole (10%, only by disk diffusion). A similar resistance pattern was observed in B. thetaiotaomicron, Bacteroides ovatus, and Parabacteroides distasonis. C. perfringens showed high resistance to clindamycin (69% and 45% by MIC methods and disk diffusion, respectively), while benzylpenicillin and metronidazole maintained over 90% activity. F. nucleatum showed high resistance to benzylpenicillin (11%), while Fusobacterium necrophorum showed alarming rates of resistance to clindamycin (12%), meropenem (16%) and metronidazole (11%).
Conclusions: This study presented an up-to-date analysis of the diagnostics and epidemiology of anaerobic bacteria in Europe, providing insights for future comparative analyses and the development of antimicrobial diagnostic and management strategies, as well as the optimization of current antibiotic treatments
Pachydermodactily – the great imitator of arthritis: a case series
No full textPachydermodactily is a rare digital fibromatosis of unknown origin, mainly affecting adolescent boys. It presents as symmetrical, painless thickening of the soft tissues, usually around the proximal interphalangeal joints (PIP). Patients often experience delayed diagnoses, receive unnecessary treatments, or are misdiagnosed with chronic inflammatory arthritis. Although the exact cause remains unclear, pachydermodactyly may be associated with repetitive mechanical trauma, such as rubbing or interlacing the fingers, which can lead to secondary skin thickening. Treatment is often not required given its benign prognosis, although some patients ask for therapy due to the cosmetic impact of the condition. The aim of this study was to present the characteristics of seven patients diagnosed with pachydermodactily at pediatric rheumatology outpatient clinics in Zagreb. Additionally, we performed a comprehensive literature review of reported cases published from 1975 to 2024 using PubMed and Google Scholar. The primary symptom observed was swelling of the soft tissues around the PIP and metacarpophalangeal joints, with some patients presenting with hyperkeratotic plaques resembling knuckle pads. One patient experienced hand pain. Clinical examination and diagnostic workup were performed (laboratory tests specific for rheumatologic diseases, radiological tests such as joint ultrasound, x-ray or magnetic resonance imaging, or skin biopsy) to exclude other conditions with similar clinical features and etiologies, such as juvenile idiopathic arthritis. None of the patients met the criteria for juvenile idiopathic arthritis according to the classification criteria of the International League of Associations for Rheumatology. Increasing awareness of pachydermodactyly and achieving accurate diagnoses can reduce unnecessary diagnostic tests, treatments, and patient anxiety
Application and effects of gene modifications mediated by a lentviral vector in the mouse brain
No full textUnos genetskog materijala i genskih preinaka važan je pristup za proučavanje i liječenje genetskih i drugih bolesti. Lentivirusni vektori ističu se kao dominatan sustav dostave u ciljane stanične linije središnjeg živčanog sustava. Glavni cilj ovog istraživanja bio je utvrditi transdukciju neurona i astrocita za njih specifično dizajniranim lentivirusnim vektorom, procjeniti uzrokuje li dostavljen sustav shRNA utišavanje gena Spry2 te utvrditi učinak utišavanja gena Spry2 nakon izazivanja ishemijskog moždanog udara u mišjem modelu. Potvrđena je uspješna transdukcija stanica lentivirusnim vektorom te je analizom kolokalizacije pokazano da lentivirusni vektori s ovojnicom VSV-G transduciraju neurone dok Tet regulirani lentivirusni vektori sa specifičnim promotorom za astrocite i ovojnicom Mokola transduciraju astrocite. Procjenom aktivacije mikroglije i receptora TLR2 pokazano je da unos lentivirusnog vektora uzrokuje kratkotrajnu aktivaciju upalnog odgovora koja je ograničena na područje unosa. Analizom genske ekspresije potvrđeno je utišavanje gena Spry2 u injektiranim regijama mišjeg mozga. Međutim, njegova smanjena ekspresija nije pridonijela značajnom smanjenju volumena ishemijske lezije i funkcionalnom oporavku nakon ishemijskog moždanog udara. Ovo istraživanje potvrdilo je da su primjenjene strategije dizajna lentivirusnih vektora učinkovit sustav dostave koji omogućava ograničenu transdukciju stanica od interesa i uspješno utišavanje gena Spry2.The delivery of genetic material or gene modification is an important approach for the study and treatment of genetic and other diseases. Lentiviral vectors are a dominant delivery system to target cell lines of the central nervous system. The aim of this study was to determine the transduction of target cells with a specifically designed lentiviral vector for the neuron and astrocyte transduction, to assess whether the delivered shRNA system causes silencing of Spry2, and to examine the effect of Spry2 silencing after ischemic stroke induction in a mouse model. Successful cell transduction with the lentiviral vector was confirmed, and colocalization analysis confirmed that VSV-G pseudotyped lentiviral vectors transduce neurons, while Tet-regulated Mokola pseudotyped lentiviral vector with astrocyte-specific promoter transduce astrocytes. Furthermore, lentiviral vector causes a short-term activation of the inflammatory response, which was restricted near the area of injection site. Silencing of the Spry2 was confirmed in the injected regions of the mouse brain. However, downregulation of Spry2 did not reduced the volume of ischemic lesion and contribute to the functional recovery after ischemia. This study confirmed that the applied design strategies of lentiviral vector are an efficient delivery system that allows restricted transduction of cells of interest and successful Spry2 silencing