Veterinary medicine - Repository of PHD, master's thesis
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Contemporary pharmacotherapy of Alzheimer's disease
No full textAlzheimerova bolest (AB) je kronična, progresivna neurodegenerativna bolest te najčešći uzrok demencije (60-70 %). Bolest karakterizira polagan tijek s konstantnim padom kognitivnih funkcija u vidu pažnje, jezika, socijalne spoznaje i prosudbe, psihomotorne brzine i drugih. Osim navedenih, s progresijom bolesti nastupaju i brojni drugi simptomi poput depresije, apatije, halucinacija, razdražljivosti, agresije i konfuzije koji znatno narušavaju obiteljsko, socijalno i profesionalno funkcioniranje oboljelih. U posljednjim desetljećima demencija poprima epidemijske razmjere te se predviđa kako će do 2050. godine u svijetu biti oboljelo 132 milijuna ljudi. Nekoliko je hipoteza o mogućem uzroku nastanka AB-a poput kolinergičke hipoteze, hipoteze amiloidne kaskade, tau hipoteze i brojnih drugih na kojima se zasnivaju mehanizmi djelovanja danas dostupnih lijekova. Današnja suvremena terapija Alzheimerove bolesti zasniva se na simptomatskom olakšavanju tegoba i produljenju kvalitete života u smislu očuvanja kognitivnih sposobnosti. Lijekovi koji se primjenjuju pripadaju skupini inhibitora acetilkolinesteraze i NMDA-antagonistima, a to su: takrin, donepezil, rivastigmin, galantamin i memantin. Temelj njihove primjene zasniva se na patohistološki dokazanoj disfunkciji kolinergičkog sustava neurotransmisije i glutamatne ekstrasinaptičke transmisije putem NMDA receptora. Uz njih, dostupni su i brojni drugi lijekovi koji, personalizirano prema potrebama pacijenta, olakšavaju popratne simptome i komorbiditete u demenciji. To su antidepresivi, anksiolitici, hipnotici, antipsihotici i drugi. Važna novost u liječenju AB-a posljednjih godina je pojava lijekova koji modificiraju tijek bolesti a koji su nakon dva desetljeća prvi novoodobreni lijekovi za AB zasad prisutni na američkom tržištu. Njihov temeljni mehanizam djelovanja zasniva se na otapanju amiloidnih plakova, patološkog supstrata u AB-u koji dovodi do gubitka sinapsi i neurotoksičnosti. Za sad su široj javnosti poznati adukanumab, lekanemab i donanemab, a u fazi kliničkih ispitivanja i procedure odobrenja nalaze se i brojni drugi. Unatoč rezervi struke zbog zabrinjavajućih nuspojava i zasad nejasnih ishoda, pojava novih terapijskih opcija budi nadu u skori pronalazak etiološke terapije koja će uspješno interferirati s patofiziologijom same bolesti i značajno mijenjati tijek ove progresivne i, zasad, terminalne bolesti.Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder and the most common cause of dementia (60-70%). The disease is characterized by a gradual decline in cognitive functions such as attention span, language, social cognition and judgment, psychomotor speed, and others. In addition to these symptoms, as the disease progresses, numerous other symptoms such as depression, apathy, hallucinations, irritability, aggression, and confusion occur, significantly impairing the familial, social, and professional functioning of patients. In recent decades, dementia has reached epidemic proportions, and it is projected that by 2050, there will be 132 million people affected worldwide. There are several hypotheses about the possible causes of AD, including the cholinergic hypothesis, the amyloid cascade hypothesis, the tau hypothesis, and others, which form the basis for the mechanisms of action of currently available drugs. Modern therapy for Alzheimer's disease is based on symptomatic relief and prolongation of quality of life by preserving cognitive abilities. The drugs used belong to the group of acetylcholinesterase inhibitors and NMDA antagonists: tacrine, donepezil, rivastigmine, galantamine, and memantine. Their application is based on histopathologically proven dysfunction of the cholinergic neurotransmission system and glutamate extrasynaptic transmission via NMDA receptors. In addition to these drugs, there are numerous others available that, personalized to the patient's needs, alleviate accompanying symptoms and comorbidities in dementia, such as antidepressants, anxiolytics, hypnotics, antipsychotics, and others. An important novelty in the treatment of AD in recent years is the emergence of disease- modifying drugs that are the first newly approved drugs for AD in two decades, currently available on the American market. Their primary mechanism of action is based on dissolving amyloid plaques, the pathological substrate in AD that leads to synapse loss and neurotoxicity. So far, known drugs include aducanumab, lecanemab, and donanemab, with numerous others in clinical trials and approval processes. Despite professional reservations due to concerning side effects and currently unclear outcomes, the emergence of new therapeutic options raises hope for the imminent discovery of an etiological therapy that will successfully interfere with the pathophysiology of the disease and significantly change the course of this progressive and currently terminal diseas
The role of cardiac biomarkers and echocardiography in risk assessment of patients with venous thromboembolic disease
No full textU ovom radu prikazana je uloga srčanih biomarkera i ehokardiografije u procjeni rizika kod bolesnika s venskom tromboembolijskom bolešću. Rad se temelji na analizi duboke venske tromboze, plućne embolije, tromboze jetrenih vena te bolesti cerebralnih vena pružajući pregled liječenja i profilakse venske tromboembolijske bolesti. Srčani biomarkeri, poput moždanog natriuretskog peptida i srčanih troponina pružaju važne informacije o ozljedi miokarda i disfunkciji desne klijetke što su česte komplikacije kod bolesnika s venskom tromboembolijskom bolešću. Uključivanje srčanih biomarkera u modele stratifikacije rizika može pomoći u razlikovanju pacijenata s niskim, srednjim i visokim rizikom te usmjeriti odluke o liječenju poboljšavajući ishode.
Ehokardiografija, kao ključna slikovna metoda u procjeni srčane funkcije kod venske tromboembolijske bolesti, bitna je u identifikaciji težine plućne embolije. Ova neinvazivna tehnika omogućuje vizualizaciju srca i procjenu funkcije desne klijetke te tlačnog opterećenja. Identifikacija povećanja desne klijetke i hipokinezije ehokardiografijom može ukazati na povećani rizik u plućnoj emboliji. Prisutnost disfunkcije desne klijetke na ehokardiografiji povezana je s većim rizikom od kratkotrajne smrtnosti što može utjecati na odabir terapije.
U zaključku, integracija srčanih biomarkera i ehokardiografije ključna je u procjeni rizika kod bolesnika s venskom tromboembolijskom bolešću. Ovi dijagnostički alati pružaju važne uvide u srčanu funkciju, hemodinamski status i prognozu pomažući kliničarima u stratifikaciji pacijenata prema njihovu riziku i optimiziranju terapijskog pristupa s ciljem poboljšanja ishoda.This paper investigates the importance of cardiac biomarkers and echocardiography in risk assessment in patients with venous thromboembolic disease. The paper is based on the analysis of deep vein thrombosis, pulmonary embolism, hepatic vein thrombosis and cerebral vein disease, providing an overview of the treatment and prophylaxis of venous thromboembolic disease. Cardiac biomarkers, such as brain natriuretic peptide and cardiac troponins, provide important information about myocardial injury, and right ventricular dysfunction, which are common complications in patients with venous thromboembolic disease. Incorporating cardiac biomarkers into risk stratification models can help differentiate low-, intermediate-, and high-risk patients and guide treatment decisions, in order to improve outcomes.
Echocardiography, as a key imaging method in assessing cardiac function in venous thromboembolic disease, plays an important role in identifying the severity of pulmonary embolism. This non-invasive technique enables visualization of the heart and assessment of right ventricular function and pressure overload. Identification of right ventricular enlargement and/or hypokinesia by echocardiography may indicate an increased risk in pulmonary embolism. The presence of right ventricular dysfunction on echocardiography is associated with a higher risk of short-term mortality, which may influence the choice of therapy.
In conclusion, the integration of cardiac biomarkers and echocardiography is essential in risk assessment in patients with venous thromboembolic disease. These diagnostic tools provide important insights into cardiac function, hemodynamic status, and prognosis, helping clinicians stratify patients according to their risk and optimize the therapeutic approach to improve outcomes
The influence of modern daily living activities on determining the optimal position for elbow arthrodesis
No full textArtrodeza lakta je kirurški zahvat kojemu je cilj operativno ukočenje humeroulnarnog zgloba. Prvenstveno je indicirana kod bolesnika s bolnim laktom kod kojih ne postoji način liječenja koji bi očuvao pokretljivost u laktu. Lakat je zglob koji pozicionira šaku u prostoru pa gubitak mobilnosti može predstavljati značajan funkcionalni deficit za pojedinca. Cilj ovog istraživanja bio je utvrditi optimalan stupanj fleksije za artrodezu lakta te usporediti naše rezultate s rezultatima prijašnjih istraživanja. Istraživanje je provedeno na Klinici za ortopediju Kliničkog bolničkog centra Zagreb i Medicinskog fakulteta Sveučilišta u Zagrebu. Ispitivala se mogućnost izvođenja aktivnosti svakodnevnog života, aktivnosti potrebnih za provođenje osobne njege i higijene te suvremenih svakodnevnih aktivnosti. Izvođenje aktivnosti je procijenjeno pomoću bodovne ljestvice koja je modificirana prema Tangu i sur. Aktivnosti su ispitivane nakon imobilizacije lakta zglobnom ortozom najprije u 30° pa zatim i u 50°, 70°, 90°, 110° i na kraju 120° . U istraživanju je sudjelovalo 30 ispitanika (12 žena i 18 muškaraca) prosječne dobi od 24 (raspon, 19 – 26) godina. Rezultati pokazuju da je najbolji rezultat za sve tri skupine aktivnosti dobiven u 90° fleksije (79,70 ± 4,11), a zatim u 110° (76,17 ± 4,01) te 70° (75,43 ± 6,64) fleksije. Osim toga, najveći postotak ispitanika uspio je izvesti sve zadane aktivnosti kada im je lakat bio fiksiran u 90° fleksije. Rezultati također ukazuju na to da je kut fleksije od 90° najpovoljniji za izvođenje suvremenih svakodnevnih aktivnosti. Prema dostupnoj literaturi, ovo je prvo istraživanje u kojem su te aktivnosti ispitivane koristeći suvremene naprave u svrhu utvrđivanja optimalnog položaja za artrodezu lakta. Ipak, zbog nemogućnosti izvođenja svih aktivnosti u jednom položaju lakta, savjetuje se konačnu odluku o kutu artrodeze lakta donijeti u dogovoru s bolesnicima, uzimajući u obzir njihove potrebe i navike.Elbow arthrodesis is the surgical fusion of the humeroulnar joint. It is primarily indicated for patients with a painful elbow where no other treatment options are available to preserve elbow mobility. The elbow determins the position of the hand in space, so loss of elbow mobility can result with significant functional impairment. The aim of this study was to determine the optimal angle of elbow flexion which can be sufficient for performing activities of daily living. The research was conducted at the Department of Orthopedics in the Clinical Hospital Center of Zagreb and the Zagreb School of Medicine. The performance of activities of daily living, activities of personal care and hygiene and modern activities of daily living was evaluated. A modified scoring system described by Tang et al. was used to evaluate the activities. The performance evaluation was conducted first without a brace and then with an elbow brace locked in 30°, 50°, 70°, 90°, 110° and 120° of flexion. The study included 30 examinees (12 female and 18 male) with a mean age of 24 (range, 19 to 26) years. The best result were achived at 90° of elbow flexion (79,70 ± 4,11) for all three activity groups, followed by 110° (76,17 ± 4,01) and 70° (75,43 ± 6,64) of flexion. Most of the examinees were able to perform all of the activities in 90° of elbow immobilisation. The 90° flexion angle was also favorable for modern daily activities performing. This is, to our knowledge, the first study that evaluated these activities using modern devices to determine the optimal angle for elbow arthrodesis. Nevertheless, patient consultation about the preferable angle is still advised, since there is no fusion angle allowing performance of all daily activities
Role of gene KRAS in the diagnosis and treatment of colorectal cancer
No full textUloga KRAS gena u dijagnostici i terapiji kolorektalnog karcinoma
Zrinka Madunić
Kolorektalni karcinom (CRC) je heterogena bolest kako na staničnoj tako i na molekularnoj razini. Mutacije gena KRAS (engl. Kirsten rat sarcoma virus) prisutne su u otprilike 40% svih slučajeva CRC-a te često rezultiraju konstitutivnom aktivacijom istoimenog proteina. Takav, promijenjeni protein djeluje kao molekularni prekidač za neprekidno poticanje signalnih putova nizvodno, što potiče proliferaciju i preživljavanje stanica, a posljedično dovodi do tumorigeneze. Pacijenti čiji CRC sadrži stanice s mutiranim genom KRAS sveukupno imaju lošiju prognozu. Postoje različite laboratorijske metode za detekciju mutacija, s naglaskom na PCR analizu u stvarnom vremenu, Therascreen KRAS kit, StripAssay i SNaPshot. Zbog prisutnosti KRAS mutacija, skupina pacijenata s CRC-om zahtijeva preciznije terapije. KRAS protein je povijesno smatran nepristupačnim za ciljanu terapiju sve do razvoja inhibitora specifičnih za KRASG12C. Imunosupresivno okruženje KRAS mutiranog CRC-a objašnjava ograničenja imunoterapije, ali ističe i potencijalne terapijske pristupe poput adoptivnog prijenosa T limfocita usmjerenih na KRAS mutant ili cjepiva za neutralizaciju proteina KRAS. Ovi obećavajući inhibitori mogu pružiti nove strategije za liječenje KRAS-mutiranog CRC-a.Role of KRAS gene in the diagnosis and treatment of colorectal cancer
Zrinka Madunić
Colorectal cancer (CRC) is a heterogeneous disease at the cellular and molecular level. Kirsten rat sarcoma virus (KRAS) gene is a frequently mutated oncogene in CRC, with mutations present in approximately 40% of all CRC cases. Mutations result in constitutive activation of the KRAS protein, which acts as a molecular switch to continuously stimulate downstream signalling pathways, promoting cell proliferation and survival, leading to tumorigenesis. Patients whose CRC contains cells with mutated KRAS have a worse prognosis overall. There are various laboratory methods for mutation detection, emphasizing real-time PCR analysis, Therascreen KRAS kit, and other methods such as StripAssay and SNaPshot. Due to the presence of KRAS mutations, this group of CRC patients requires more precise therapies. The KRAS protein was historically considered inaccessible to targeted therapy until the development of KRASG12C-specific inhibitors. The immunosuppressive environment of KRAS mutated CRC explains the limitations of immunotherapy, but also highlights potential therapeutic approaches such as adoptive transfer of T lymphocytes targeting the KRAS mutant or vaccines to neutralize the KRAS protein. These promising inhibitors may provide new strategies for the treatment of KRAS-mutated CRC
Comparison of outcomes of spontaneously conceived twin pregnancies and twin pregnancies after in vitro fertilization
No full textU zadnjih par desetljeća medicinski pomognuta oplodnja (MPO), u koju spada i postupak izvantjelesne oplodnje (IVF), značajno se razvila. Zahvaljujući tome, uspjeli su se smanjiti rizici i nepoželjni ishodi postupaka MPO-a. S obzirom da su blizanačke trudnoće rizičnije od jednoplodnih, provedena su mnoga istraživanja u kojima su se razmatrali njihovi ishodi i rizici. Unatoč mnogim oprečnostima i razlikama u provedenim studijama koje su uspoređivale ishode spontano začetih blizanačkih trudnoća i blizanačkih trudnoća iz postupka IVF-a, sve studije pokazale su da postupak IVF-a dodatno povećava rizik od prijevremenog poroda, a time i broj hospitalizacija na novorođenačkom odjelu intenzivne njege. U današnje vrijeme blizanačka trudnoća iz postupka MPO-a može se izbjeći, a u tu svrhu Europsko društvo za humanu reprodukciju i embriologiju izdalo je nove preporuke za specijaliste humane reprodukcije. Navedene preporuke nastale su na temelju usporedbe mogućih koristi i rizika izbornog prijenosa jednog i dva embrija s obzirom na psihosocijalne, financijske i kliničke čimbenike pacijentica, te regulatornih okvira i politika naknada u europskim državama u kojima se izvodi MPO. Nakon uzimanja svih čimbenika u obzir, smjernice preporučuju izborni prijenos jednog umjesto više embrija, što smanjuje mogućnost za blizanačku trudnoću kao ishod MPO-a, a time i izbjegavanje komplikacija koje nose blizanačke trudnoće.Over the past few decades, assisted reproductive techniques (ART), including the process of in vitro fertilization (IVF), has significantly developed. Thanks to these advancements, the risks and undesirable outcomes of the procedure have been reduced. Twin pregnancy, being one of them, is inherently more risky than singleton pregnancy, and it has long been debated whether the process of in vitro fertilization makes it even riskier. Despite many contradictions and differences between studies comparing the outcomes of spontaneously conceived twin pregnancies and twin pregnancies from in vitro fertilization, all have shown that the in vitro fertilization process only further increases the risk of preterm birth, and consequently the number of hospitalizations in the neonatal intensive care unit. Nowadays, twin pregnancies from ART can be avoided, and for this purpose, the European Society of Human Reproduction and Embryology (ESHRE) has issued new recommendations for specialists in human reproduction. These recommendations compare all possible benefits and disadvantages of elective single embryo transfer (eSET) and double embryo transfer (DET) considering the psychosocial, financial, and clinical factors of the patients, as well as the policy and rights of the country in which the MAR is performed. The guideline's recommendation is, after taking all factors into account, a single elective embryo transfer (eSET) instead of multiple ones, which reduces the chance of twin pregnancy as an outcome of ART and avoids the complications associated with twin pregnancies
The impact of microinvasive surgical treatment of preinvasive and early invasive malignant lesion of the cervix on pregnancy outcomes
No full textEkscizija transformacijske zone cerviksa velikom petljom (LLETZ) i konizacija hladnim nožem (CKC) metode su ekscizijskog kirurškog liječenja preinvazivnih i invazivnih promjena vrata maternice. Obje metode su sigurne i učinkovite te objedinjuju dijagnostiku i terapiju u jednom aktu. Cilj ovog istraživačkog rada bio je istražiti utjecaj navedenih tehnika na ishode trudnoće. Istraživanje je analiziralo ishode trudnoće kod 84 ispitanice koje su povrgnute navedenim zahvatima prije trudnoće. Od toga, 73 (86.9%) su imale LLETZ, a 11 (13.1%) CKC. Paritet nije pokazao statistički značajnu razliku, ali klinički je važno da je veći postotak višerotki u CKC grupi. Najčešće dijagnosticirane lezije su bile CIN 3 (51.14%) i CIN 2 (28.41%). Postoji statistički značajna povezanost između vrste zahvata, pravovremenosti poroda i načinu dovršenja poroda. CKC skupina ima veći rizik za prijevremeni porod (OR=10.76) i carski rez (OR=10.96) u usporedbi s LLETZ (OR=1.03). Iako su rezultati statistički značajni, mali uzorak CKC skupine može utjecati na preciznost procjena. Potrebna su dodatna istraživanja s većim brojem ispitanica kako bi se potvrdila značajnost ovih rezultata. CKC nosi veći rizik od komplikacija u trudnoći i porodu u usporedbi s LLETZ zahvatom, stoga je ključno pažljivo praćenje i savjetovanje pacijentica kako bi se smanjili rizici i osigurali optimalni ishodi trudnoće.Large loop excision of the cervical transformation zone (LLETZ) and cold knife conization (CKC) are excisional surgical methods for treating preinvasive and invasive changes in the cervix. Both methods are safe and effective, combining diagnostics and therapy in a single procedure. This research aimed to investigate the impact of these techniques on pregnancy outcomes. The study analyzed pregnancy outcomes in 84 patients who underwent these procedures before pregnancy. Of these, 73 (86.9%) had LLETZ, and 11 (13.1%) had CKC. Parity did not show a statistically significant difference, but it is clinically important that there is a higher percentage of multiparas in the CKC group. The most commonly diagnosed lesions were CIN 3 (51.14%) and CIN 2 (28.41%). There is a statistically significant association between the type of procedure, the timing of delivery, and the mode of delivery. The CKC group has a higher risk for preterm delivery (OR=10.76) and cesarean section (OR=10.96) compared to LLETZ (OR=1.03). Although the results are statistically significant, the small sample size of the CKC group may affect the precision of the estimates. Further research with a larger number of patients is needed to confirm the significance of these results. CKC carries a higher risk of pregnancy and delivery complications compared to LLETZ, so careful monitoring and counseling of patients is crucial to reduce risks and ensure optimal pregnancy outcomes
Psychodynamics of love relationships
No full textOvaj pregledni rad bavi se problematikom ljubavnih odnosa iz perspektive psihodinamike. U prvom dijelu rada opisane su Freudove klasične teorije. Topografska koja dijeli psihički aparat na svjesno i nesvjesno te strukturna teorija koja mu pridodaje podjelu na id, ego i superego. Zatim prati dijete kroz ključne razvojne faze i značajne događaje. Za to vrijeme kontroverzni psihoseksualni razvoj djeteta pomiče granice shvaćanja seksualnosti. Teorija objektnih odnosa opisat će značaj ranih odnosa koji kroz unutrašnje reprezentacije postaju nazobilazna postaja u analizi kasnijih odnosa, dok je teorija privrženosti zanimajući se za odnos djeteta s majkom pokazala da postoji korelat s modelima privrženosti u ljubavnim odnosima odraslih. Tijekom odrastanja za vrijeme rane adolescencije čestim zaljubljivanjem mlada osoba uči razliku između idealizacije i stvarnosti. Ulaskom u ljubavni odnos nastupa iznimno važno nesvjesno odigravanje koje je izvor dinamike para. U nizu nesvjesnih odigravanja par se suočava s edipalnim parom iz više perspektiva. Tu su u podlozi želje za identifikacijom s parom, za njegovim uništenjem, pobjedom nad rivalom ili pronalazak željenog ideala. Par izgrađuje vlastiti superego kao svojevrsnu obranu od vanjskih i unutarnjih prijetnji. Ovisno o zrelosti superega bit će vidljiv spektar aktivacija superega od poželjnih do patoloških. Niz karakteristika razlikuje zreli, stabilni odnos od nezrelih. Između ostalog zreli odnos ima kvalitete kao što su temeljno povjerenje, poniznost i zahvalnost za drugu osobu i njezinu ljubav, kapacitet za oprost i druge karakteristike opisane u radu. Patologija ljubavnih odnosa vezana je za poremećaje ličnosti u kojima se često nalaze problemi s objektnim odnosima, krivnjom, empatijom, te je odnos u konačnici nestabilniji i manje zadovoljavajući.This review paper addresses the complexities of romantic relationships from a psychodynamic perspective. The first part of the paper describes Freud's classical theories: the topographical model, which divides the psychic apparatus into the conscious and the unconscious, and the structural theory, which adds the division into the id, ego, and superego. It then follows the child through key developmental stages and significant events, highlighting the controversial psychosexual development of the child, which challenges traditional understandings of sexuality. Object relations theory will explain the significance of internal events that form the foundation for future relationships, while attachment theory, focusing on the child's relationship with the mother, demonstrates a correlation with attachment patterns in adult romantic relationships. During early adolescence, frequent infatuations teach young individuals the distinction between idealization and reality. Entering a romantic relationship involves critically important unconscious enactments that drive the couple's dynamics. In a series of unconscious reenactments, the couple confronts the Oedipal pair from multiple perspectives, including desires for identification with the pair, its destruction, victory over a rival, or the pursuit of an ideal. The couple constructs its own superego as a defense against external and internal threats. Depending on the maturity of the superego, the spectrum of superego activations will range from desirable to pathological. Several characteristics distinguish a mature, stable relationship from immature ones. Among others, a mature relationship possesses qualities such as fundamental trust, humility, gratitude for the other person and their love, the capacity for forgiveness, and other traits described in the paper. The pathology of romantic relationships is linked to personality disorders, which often involve issues with object relations, guilt, empathy, and ultimately lead to more unstable and less satisfying relationships
Waldenström macroglobulinemia – between lymphoma and myeloma
No full textWaldenströmova makroglobulinemija je rijedak indolentni B-stanični limfom koji je karakteriziran prisutnošću monoklonalnog imunoglobulina M u serumu i klonalnom proliferacijom limfoplazmocitoidnih stanica u koštanoj srži. Najčešće pogađa stariju populaciju, posebno muškarce bijele rase, s prosječnom dobi dijagnoze između 63 i 73 godine. Patogeneza Waldenströmove makroglobulinemije uključuje genetske, imunološke i okolišne čimbenike, a ključnu ulogu igra somatska mutacija MYD88L265P, prisutna u većini slučajeva. Ova mutacija aktivira signalne putove koji promiču preživljavanje i proliferaciju tumorskih stanica. Kliničke manifestacije Waldenströmove makroglobulinemije mogu uključivati simptome uzrokovane infiltracijom koštane srži, poput anemije, trombocitopenije i neutropenije, kao i simptome povezane s visokom razinom imunoglobulina M, što može dovesti do hiperviskoznosti, periferne neuropatije i drugih komplikacija. Waldenströmova makroglobulinemija je klinički i patološki blisko povezana s drugim B-staničnim tumorima, posebno s multiplim mijelomom i drugim vrstama limfoma. S limfomima dijeli infiltraciju CD20+ limfocitnim stanicama u koštanoj srži i drugim organima poput limfnih čvorova, jetre i slezene, dok s multiplim mijelomom dijeli infiltraciju koštane srži plazma stanicama i proizvodnju monoklonalnog imunoglobulina, u ovom slučaju IgM. Liječenje uključuje kemoimunoterapiju s rituksimabom, inhibitore Brutonove tirozin kinaze, inhibitore proteasoma i kod mlađih pacijenata s refraktornom ili recidivnom bolesti, autolognu transplantaciju matičnih stanica.Terapijski ciljevi su usmjereni na kontrolu simptoma, smanjenje rizika oštećenja organa i produljenje preživljavanja. Radi se o neizlječivoj bolesti, s medijanom preživljenja oko 10 godina.Waldenström macroglobulinemia is a rare indolent B-cell lymphoma characterized by monoclonal immunoglobulin M in the serum and clonal proliferation of lymphoplasmacytic cells in the bone marrow. It predominantly affects the older population, especially white males, with an average age at diagnosis between 63 and 73 years. The pathogenesis of Waldenström macroglobulinemia involves genetic, immunological, and environmental factors, with the somatic MYD88L265P mutation playing a crucial role in most cases. This mutation activates signaling pathways that promote the survival and proliferation of tumor cells. Clinical manifestations can include symptoms caused by bone marrow infiltration, such as anemia, thrombocytopenia, and neutropenia, and symptoms associated with high immunoglobulin M levels, which can lead to hyperviscosity, peripheral neuropathy, and other complications. Waldenström macroglobulinemia is clinically and pathologically closely related to other B-cell malignancies, particularly multiple myeloma and other types of lymphoma. It is characterized by the infiltration of CD20+ lymphocytic cells in the bone marrow and other organs such as lymph nodes, liver, and spleen like lymphomas. Additionally, the infiltration of bone marrow by plasma cells and the production of monoclonal immunoglobulin resembles multiple myeloma, particularly IgM myeloma. Treatment includes chemoimmunotherapy with rituximab, Bruton’s tyrosine kinase inhibitors, proteasome inhibitors, and autologous stem cell transplantation for younger patients with refractory or relapsed disease. The therapeutic goals aim to control symptoms, reduce the risk of organ damage, and prolong survival. It is an incurable disease, but the median survival rate is 10 years
Mechanical ventilation during general anaesthesia
No full textMehanička ventilacija je ključna medicinska intervencija koja se koristi kod pacijenata koji nisu u stanju održati dostatnu ventilaciju zbog akutnog respiratornog zatajenja, kroničnih respiratornih stanja, anestezije tijekom operacije ili teških trauma. Mehanička ventilacija je proces dostavljanja plinova u pluća i odvođenja plinova iz pluća pomoću uređaja koji se zove ventilator. U cilju održavanja primjerenih parcijalnih tlakova kisika (PaO2) i ugljikovog dioksida (PaCO2) u krvi, ventilator se može postaviti na različite načine, ovisno o potrebama pacijenta. Ovi načini rada variraju od potpuno kontrolirane ventilacije, gdje stroj preuzima cijeli proces disanja, do potpomognutih načina, gdje pacijent započinje udah, a ventilator ga podržava. Ključni parametri kao što su udisajni volumen (eng. tidal volume), respiratorna frekvencija (eng. respiratory frequency) i koncentracija kisika (eng. fraction of inspired oxygen) pažljivo se prilagođavaju kako bi se optimizirala respiratorna funkcija i prevenirale moguće komplikacije. Razumijevanje mehaničke ventilacije zahtijeva poznavanje respiratorne fiziologije, mehanike disanja i principa izmjene plinova. Uz to, zdravstveni djelatnici trebaju biti upoznati s postavkama i mogućnostima svakog ventilatora kojim rukuju, kako bi osigurali učinkovitu i sigurnu ventilaciju. Kako tehnologija napreduje, noviji ventilatori nude sofisticirane značajke koje poboljšavaju ishode liječenja, čineći mehaničku ventilaciju vitalnom komponentom moderne anesteziologije i intenzivne medicine.Mechanical ventilation is a crucial medical intervention used in patients who are unable to maintain adequate ventilation due to acute respiratory failure, chronic respiratory conditions, anesthesia during surgery, or severe trauma. Mechanical ventilation is the process of delivering gases to the lungs and removing gases from the lungs using a device called a ventilator. To maintain appropriate partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) in the blood, the ventilator can be set in various ways depending on the patient's needs. These modes of operation range from fully controlled ventilation, where the machine takes over the entire breathing process, to assisted modes, where the patient initiates a breath, and the ventilator supports it. Key parameters such as tidal volume, respiratory frequency, and oxygen concentration are carefully adjusted to optimize respiratory function and prevent possible complications. Understanding mechanical ventilation requires knowledge of respiratory physiology, breathing mechanics, and the principles of gas exchange. Additionally, healthcare professionals need to be familiar with the settings and capabilities of each ventilator they handle to ensure effective and safe ventilation. As technology advances, newer ventilators offer sophisticated features that improve treatment outcomes, making mechanical ventilation a vital component of modern anesthesiology and intensive care medicine
Pancreatic and systemic effects of glucagon-like peptide-1 agonist therapy
No full textTerapijski pristup šećernoj bolesti tipa 2 sve češće uključuje terapiju temeljenu na inkretinskom sustavu, posebice analoge glukagonu sličnog peptida-1 (GLP-1). Ti pripravci oponašaju sekreciju endogeno proizvedenog inkretinskog hormona GLP-1, dovodeći do pojačane sekrecije inzulina i slabijeg lučenja glukagona, što je bitno za održavanje homeostaze glukoze. Pankreatični učinci analoga GLP-1 receptora očituju se pojačanim lučenjem inzulina iz β-stanica gušterače ovisnog o glukozi i inhibicijom lučenja glukagona iz α-stanica otočića gušterače. Proliferacija β-stanica, inhibicija apoptoze i pojačana sinteza inzulina još su neki od povoljnih učinaka na tkivo gušterače. Osim pankreatičnih učinaka, analozi GLP-1R pokazuju neke sustavne prednosti, osobito u protekciji kardiovaskularnog sustava i smanjenju tjelesne težine. Klinička istraživanja provedena u svrhu dokaza kardiovaskularne sigurnosti, pokazala su da analozi GLP-1 receptora smanjuju rizik od velikog štetnog kardiovaskularnog događaja, koji uključuje smrt kardiovaskularnog uzroka, infarkt miokarda ili moždani udar bez smrtnog ishoda. Kardioprotektivne učinke ostvaruje preko nekoliko mehanizama uključujući regulaciju glikemije, krvnog tlaka, razine lipida i tjelesne težine. Također, analozi GLP-1R pokazali su i renoprotektivna svojstva usporavajući progresiju dijabetičke nefropatije očuvanjem eGFR-a i smanjenjem albuminurije. Terapija analozima GLP-1 receptora utječe i na funkciju gastrointestinalnog sustava. Usporava pražnjenje želuca i motilitet crijeva te pruža osjećaj sitosti što sve zajedno rezultira smanjenim unosom hrane. Ta prednost iskorištava se za bolju kontrolu, odnosno redukciju tjelesne težine. Na kraju, noviji podaci pružaju informaciju o neuroprotektivnom djelovanju i ublažavanju kognitivnih poremećaja, pritom ostavljajući prostora za ostvarivanje terapijskog potencijala i na tom području.The therapeutic approach to type 2 diabetes mellitus increasingly includes therapy based on the incretin system, especially glucagon-like peptide-1 agonists. These agents mimic the secretion of the endogenously produced incretin hormone GLP-1, leading to increased insulin secretion and suppressed glucagon secretion, which is essential for maintaining glucose homeostasis. The pancreatic effects of GLP-1 receptor analogues are manifested by increased glucose-dependent insulin secretion from pancreatic β-cells and inhibition of glucagon secretion from α-cells of the pancreatic islets. β-cell proliferation, inhibition of apoptosis and enhanced insulin synthesis are some of the beneficial effects on pancreatic tissue. Beyond their pancreatic effects, GLP 1R analogues show some systemic benefits, especially in the protection of the cardiovascular system and weight loss. Clinical studies conducted to prove cardiovascular safety have shown that GLP-1 receptor analogues reduce the risk of a major adverse cardiovascular event, which includes cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. It exerts cardioprotective effects through several mechanisms, including the regulation of glycemia, blood pressure, lipid levels and body weight. Also, GLP-1R analogues have shown renal protection by slowing the progression of diabetic nephropathy by preserving eGFR and reducing albuminuria. Therapy with GLP-1 receptor analogues also affects the function of the gastrointestinal system. It slows down gastric emptying and intestinal motility and provides a feeling of satiety, which all together results in reduced food intake. This advantage is used for better body weight management. Finally, recent data provide information on neuroprotective effects and alleviation of cognitive disorders, while leaving room for the realization of therapeutic potential in this area as well