Veterinary medicine - Repository of PHD, master's thesis
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Tissue engineering and future directions in regenerative medicine for knee cartilage repair: a comprehensive review
This review evaluates the current landscape and future directions of regenerative medicine for knee cartilage repair, with a particular focus on tissue engineering strategies. In this context, scaffold-based approaches have emerged as promising solutions for cartilage regeneration. Synthetic scaffolds, while offering superior mechanical properties, often lack the biological cues necessary for effective tissue integration. Natural scaffolds, though biocompatible and biodegradable, frequently suffer from inadequate mechanical strength. Hybrid scaffolds, combining elements of both synthetic and natural materials, present a balanced approach, enhancing both mechanical support and biological functionality. Advances in decellularized extracellular matrix scaffolds have shown potential in promoting cell infiltration and integration with native tissues. Additionally, bioprinting technologies have enabled the creation of complex, bioactive scaffolds that closely mimic the zonal organization of native cartilage, providing an optimal environment for cell growth and differentiation. The review also explores the potential of gene therapy and gene editing techniques, including CRISPR-Cas9, to enhance cartilage repair by targeting specific genetic pathways involved in tissue regeneration. The integration of these advanced therapies with tissue engineering approaches holds promise for developing personalized and durable treatments for knee cartilage injuries and osteoarthritis. In conclusion, this review underscores the importance of continued multidisciplinary collaboration to advance these innovative therapies from bench to bedside and improve outcomes for patients with knee cartilage damage
Cardiac arrest of cardiogenic origin
Srčani zastoj kardiogenog podrijetla, iznenadni prestanak srčane aktivnosti zbog srčanih uzroka,
predstavlja značajan javnozdravstveni izazov. Ovaj diplomski rad govori o ključnim
komponentama kardiogenog srčanog zastoja, s naglaskom na mehanizmima, epidemiologiji,
protokolima liječenja i preventivnim strategijama. Sustav srčane provodljivosti ključan je za
održavanje ritmičnih i koordiniranih kontrakcija. Diplomski rad daje kratki pregled fiziologije
provodnog sustava srca, te ulogu njegovih komponenti u normalnim i patološkim stanjima.
Patofiziološki mehanizmi koji najčešće dovode do srčanog zastoja kategorizirani su u
abnormalnu automatičnost, trigeriranu aktivnost i reentry mehanizme. Abnormalna
automatičnost uključuje spontanu depolarizaciju kardiomiocita, trigerirana aktivnost povezana je
s naknadnim depolarizacijama, a reentry mehanizmi, najčešći uzrok aritmija, uključuju kruženje
akcijskog potencijala. Prevalencija i ishodi srčanog zastoja variraju ovisno o mjestu
(izvanbolnički u odnosu na bolnički) i karakteristikama pacijenta. Glavni kardiogeni uzroci
srčanog zastoja uključuju koronarnu arterijsku bolest i kardiomiopatije. Naslijeđene kanalopatije,
poput sindroma dugog QT a, sindroma kratkog QT a i Brugada sindroma, također igraju
značajnu ulogu. Ova stanja mogu predisponirati pojedince za maligne aritmije, što zahtijeva
sveobuhvatne dijagnostičke i terapijske strategije. Učinkovita reanimacija ključna je za
preživljavanje nakon srčanog zastoja. Bitno je naglasiti važnost lanca preživljavanja, koji
uključuje rano prepoznavanje i obaviještavanje hitnih službi, ranu kardiopulmonalnu reanimaciju
(CPR), brzu defibrilaciju, napredne tehnike reanimacije i post reanimacijsku skrb. Protokoli
osnovnog održavanja života (BLS) fokusiraju se na visokokvalitetne kompresije prsnog koša i
ventilaciju, dok protokoli naprednog održavanja života (ALS) dodatno uključuju postavljanje
naprednog dišnog puta, defibrilaciju, intravenske lijekove i srčani monitoring. Pravovremena
defibrilacija u slučajevima ventrikularne fibrilacije ili ventrikularnoj tahikardiji bez pulsa
posebno je istaknuta. Post reanimacijska skrb ima za cilj stabilizirati pacijenta, spriječiti daljnje
nepoželjne srčane ishode i optimizirati neurološke ishode. To uključuje ventilacijsku i
cirkulatornu potporu, ciljano upravljanje temperaturom radi smanjenja neuroloških oštećenja i
kontinuirano praćenje komplikacija poput ponovnih aritmija ili disfunkcije miokarda. Naglašava
se i važnost multidisciplinarnog pristupa u postreanimacijskoj skrbi kako bi se poboljšalo
preživljavanje i funkcionalni oporavak. Identifikacija osoba u riziku od iznenadne srčane smrti
ključna je za učinkovitu prevenciju. Dipomski rad raspravlja o stratifikaciji rizika u raznim
populacijama, uključujući one s ishemijskom kardiomiopatijom, dilatacijskom
kardiomiopatijom, hipertrofičnom kardiomiopatijom i primarnim elektrofiziološkim
poremećajima. Alati poput elektrokardiograma (EKG), ehokardiografije i genetskog testiranja
koriste se za procjenu čimbenika rizika. Preventivne strategije obuhvaćaju promjene životnog
stila, farmakološke pristupe i implantabilne uređaje poput ICD a. Primarna prevencija fokusira
se na smanjenje učestalosti srčanih zastoja u visokorizičnim populacijama, dok sekundarna
prevencija ima za cilj spriječiti ponavljanje u osoba koje su već doživjele srčani zastoj. Ovaj
diplomski rad daje sveobuhvatan pregled kardiogenog srčanog zastoja, pokriva jući njegove
temeljne mehanizme i uzroke, trenutne protokole liječenja i preventivne mjere. Razumijevanje
ovih komponenti ključno je za poboljšanje stopa preživljavanja i ishoda kod osoba pogođenih
ovim po život opasnim stanjem.Cardiogenic cardiac arrest, the sudden cessation of heart activity due to cardiac causes,
represents a significant public health challenge. This thesis discusses the key components of
cardiogenic cardiac arrest, with emphasis on the mechanisms, epidemiology, treatment protocols,
and preventive strategies. The heart's conduction system is crucial for maintaining rhythmic and
coordinated contractions. The thesis provides a brief overview of the physiology of the cardiac
conduction system and the role of its components in normal and pathological conditions.
Pathophysiological mechanisms that most commonly lead to cardiac arrest are categorized into
abnormal automaticity, triggered activity, and reentry mechanisms. Abnormal automaticity
involves spontaneous depolarization of cardiomyocytes, triggered activity is associated with
afterdepolarizations, and reentry mechanisms, the most common cause of arrhythmias, involve
the looping of action potential. The prevalence and outcomes of cardiac arrest vary depending on
the setting (out of hospital versus in hospital) and patient characteristics. Major cardiogenic
causes of cardiac arrest include coronary artery disease and cardiomyopathies. Inherited
channelopathies, such as long QT syndrome, short QT syndrome, and Brugada syndrome, also
play a significant role. These conditions can predispose individuals to malignant arrhythmias,
requiring comprehensive diagnostic and therapeutic strategies. Effective resuscitation is crucial
for survival following cardiac arrest. It is essential to emphasize the importance of the chain of
survival, which includes early recognition and notification of emergency services, early
cardiopulmonary resuscitation (CPR), rapid defibrillation, advanced resuscitation techniques,
and post-resuscitation care. Basic Life Support (BLS) protocols focus on high-quality chest
compressions and ventilation, while Advanced Life Support (ALS) protocols additionally
include advanced airway management, defibrillation, intravenous medications, and cardiac
monitoring. Timely defibrillation in cases of ventricular fibrillation or pulseless ventricular
tachycardia is particularly highlighted. Post-resuscitation care aims to stabilize the patient,
prevent further adverse cardiac outcomes, and optimize neurological outcomes. This includes
ventilatory and circulatory support, targeted temperature management to reduce neurological
damage, and continuous monitoring for complications such as recurrent arrhythmias or
myocardial dysfunction. The importance of a multidisciplinary approach in post-resuscitation
care is also emphasized to improve survival and functional recovery. Identifying individuals at
risk of sudden cardiac death is crucial for effective prevention. The thesis discusses risk
stratification in various populations, including those with ischemic cardiomyopathy, dilated
cardiomyopathy, hypertrophic cardiomyopathy, and primary electrophysiological disorders.
Tools such as electrocardiograms (ECG), echocardiography, and genetic testing are used to
assess risk factors. Preventive strategies encompass lifestyle modifications, pharmacological
approaches, and implantable devices like ICDs. Primary prevention focuses on reducing the
incidence of cardiac arrests in high-risk populations, while secondary prevention aims to prevent
recurrence in individuals who have already experienced a cardiac arrest. This thesis provides a
comprehensive overview of cardiogenic cardiac arrest, covering its underlying mechanisms and
causes, current treatment protocols, and preventive measures. Understanding these components
is crucial for improving survival rates and outcomes in individuals affected by this life-threatening condition
Systemic inflammatory response in the perioperative period
Operativni postupak vodi do složenog odgovora nativnog i adaptivnog imunosnog
sustava. Kirurški stresni odgovor na sistemskoj razini uzrokuje imunosupresiju, dok lokalno
nastaje upala potaknuta izlučivanjem alarmina. Pretjerano otpuštanje alarmina može dovesti do
nereguliranog postoperativnog upalnog odgovora s povećanim rizikom za razvoj infekcija,
sindroma sistemskog upalnog odgovora i sepse.
Na upalni odgovor mogu djelovati brojni čimbenici, ponajprije kirurški i anesteziološki
postupci. Trajanje operacije, manipulacija i oštećenje tkiva izravno su proporcionalni jačini
kirurškog stresnog odgovora zbog čega se savjetuje primjena minimalno invazivne kirurgije
kada je to moguće. Anestetici i anesteziološke tehnike uključeni su u kompleksnu interakciju s
perioperativnim imunosnim odgovorom. Imunosupresivan utjecaj inhalacijskih anestetika u
slučajevima pretjeranog upalnog odgovora ili ishemijsko-reperfuzijske ozljede može biti
poželjan. Međutim kod već imunokompromitiranih i onkoloških pacijenata treba tražiti načine
ublažavanja njihovog učinka na imunosni odgovor primjenom regionalne anestezije ili
propofola. Međutim, preporuka je brojnih autora provedba dodatnih istraživanja kako bi se
dosadašnja saznanja povezala s kliničkim implikacijama.
Učinci pojedinih anestetika i adjuvantnih lijekova kao i učinci pojedinih tehnika na imunološki
sustav u perioperativnom razdoblju trebali bi biti uključeni u anesteziološki postupak donošenja
odluka. Cilj je ovog rada ponuditi trenutna saznanja o imunomodulacijskom djelovanju
kirurškog i anesteziološkog postupka te kako ih modificirati u korist boljeg postoperativnog
ishoda.The operative procedure leads to a complex response from the innate and adaptive
immune systems. The surgical stress response at the systemic level causes immunosuppression,
while locally, inflammation is triggered by the release of alarmins. Excessive release of
alarmins can lead to a dysregulated postoperative inflammatory response, increasing the risk of
developing infections, systemic inflammatory response syndrome, and sepsis.
Numerous factors can influence the inflammatory response, primarily surgical and anesthetic
procedures. The duration of surgery, tissue manipulation, and tissue damage are directly
proportional to the intensity of the surgical stress response, which is why minimally invasive
surgery is advised whenever possible. Anesthetics and anesthetic techniques are involved in the
complex interaction with the perioperative immune response. The immunosuppressive effect of
inhalational anesthetics in cases of excessive inflammatory response or ischemia-reperfusion
injury can be desirable. However, in immunocompromised and oncological patients, it is
necessary to seek ways to mitigate their impact on the immune response through the use of
regional anesthesia or propofol. Nonetheless, many authors recommend further research to
connect current knowledge with clinical implications.
The effects of specific anesthetics and adjuvant drugs, as well as the effects of certain techniques
on the immune system in the perioperative period, should be included in the anesthetic decisionmaking process. This paper aims to provide a review of current knowledge on the
immunomodulatory effects of surgical and anesthetic procedures and how to modify them to
achieve better postoperative outcomes
Stem cells in aesthetic and regenerative surgery
Primjena matičnih stanica u estetskoj i regenerativnoj kirurgiji s vremenom je postala sve više prihvatljivija i popularnija. Matične stanice imaju sposobnost samoobnove, no pokazuju i potencijal diferencijacije u različite tipove drugih stanica. Matične stanice se koriste u raznim grana medicine, te je njihova primjena raznolika. Omogućuju razumijevanje patogeneze mnogih bolesti, koriste se u ispitivanju lijekova, te kao terapija kod degenerativnih, kroničnih i upalnih bolesti. Također nadomještaju dijelove tkiva i organa koji su oštećeni ili omogućuju potpunu regeneraciju istih. U estetskoj i regenerativnoj kirurgiji najviše se upotrebljavaju matične stanice podrijetlom iz masnog tkiva jer su dostupne, jednostavne za izolaciju, te imaju velik potencijal diferencijacije u masne stanice. Lipotransfer je procedura kojom se prikuplja masno tkivo s mjesta gdje je estetski nepoželjno, te se nakon prikupljanja obrađuje i transferira na željeno mjesto. Lipotransfer se može provoditi s matičnim stanicama i bez matičnih stanica. Prednost korištenja matičnih stanica zajedno s lipotransferom je ta što matične stanice pridonose dugotrajnosti transferirane masti. Njihova funkcija je proadipogena i proangiogena. U estetskoj kirurgiji matične stanice se najviše koriste u svrhu povećanja dojki. Povećanje dojki se provodi lipotransferom s matičnim stanicama ili kao hibridna operacija. Također koriste se u rekonstrukciji dojke nakon mastektomije i radioterapije. Danas se lipotransfer s matičnim stanicama često koristi u svrhu pomlađivanja, povećanja usana, te u korekciji deformacija čeljusti. U regenerativnoj kirurgiji matične stanice koriste se u liječenju ožiljaka i fibroze. Matične stanice imaju široki terapijski potencijal u estetskoj i regenerativnoj kirurgiji. Daljnja istraživanja mogla bi doprinijeti boljem razumijevanju njihove primjene i razvoju novih terapijskih strategija.The use of stem cells in cosmetic and regenerative surgery has become more acceptable and popular over time. Stem cells have the ability to self-renew, but they also show the potential to differentiate into different types of other cells. Stem cells are used in a variety of medical fields, and their application is diverse. They enable the understanding of the pathogenesis of many diseases, are used in drug testing and as therapy for degenerative, chronic, and inflammatory diseases. They also replace damaged parts of tissues and organs or allow for their complete regeneration. In aesthetic and regenerative surgery, stem cells derived from adipose tissue are mostly used because they are available, easy to isolate, and have a great potential for differentiation into fat cells. Lipotransfer is a procedure by which fat tissue is collected from a place where it is aesthetically undesirable, and after it is collected, it is processed and transferred to the desired place. Lipotransfer can be performed with or without stem cells. The advantage of using stem cells together with lipotransfer is that the stem cells contribute to the longevity of the transferred fat. Their function is proadipogenic and proangiogenic. The most common use of stem cells in aesthetic surgery is for breast augmentation. Breast augmentation is done either through stem cell lipotransfer or hybrid surgery. They are also used in breast reconstruction after mastectomy and radiation therapy. Today, stem cell lipotranfer is often used to correct wrinkles, restore volume in the cheekbones and cheeks, reduce dark circles, improve skin tone, elasticity and quality, enlarge lips, and correct jaw deformities. In regenerative surgery, stem cells are used in the treatment of scars and fibrosis. Stem cells have a wide therapeutic potential in aesthetic and regenerative surgery. Further research could contribute to a better understanding of their applications and the development of new therapeutic strategies
Principles of asthma treatment and treatment complications
Astma je kronična upalna bolest dišnih puteva karakterizirana simptomima poput piskanja, zaduhe, stezanja u prsima i kašlja. Globalan je javnozdravstveni problem čija etiologija još uvijek nije do kraja razjašnjena. Dijagnoza astme postavlja se na temelju detaljno uzete anamneze i dokaza hiperreaktivnosti. Liječenje astme temelji se na kombinaciji farmakoloških i nefarmakoloških metoda. Farmakološke metode uključuju različite skupine lijekova kao što su inhalacijski kortikosteroidi (ICS), beta-agonisti, muskarinski antagonisti, antagonisti leukotrienskih receptora, metilksantini, stabilizatori mastocita i biološka terapija. Svaka od ovih skupina ima specifičan mehanizam djelovanja i koristi se ovisno o težini i specifičnostima astme kod pojedinih pacijenata. Stupnjevit pristup liječenju astme preporučuje prilagodbu terapije ovisno o težini i kontroli bolesti. Blaga i umjerena astma mogu se liječiti kombinacijom ICS i dugodjelujućih beta-agonista (LABA). Teška astma zahtjeva visoke doze lijekova ili dodatne terapije kako bi se postigla adekvatna kontrola. Nefarmakološko liječenje uključuje strategije poput izbjegavanja okidača astme, redovite tjelesne aktivnosti i kontrole tjelesne težine. Edukacija pacijenata o pravilnoj uporabi inhalera, prepoznavanju simptoma i upravljanju okidačima ključna je za dugoročni uspjeh terapije. Liječenje astme sa sobom nosi i određene komplikacije. Tako ICS mogu dovesti do razvoja oralne kandidijaze, disfonije i kašlja, dok beta-agonisti dovode do tahikardije i tremora. Najviše neželjenih učinaka imaju oralni kortikosteroidi čija dugotrajna upotreba nepovoljno djeluje na kožu, oči, imunološki, muskuloskeletalni i kardiovaskularni sustav.Asthma is a chronic inflammatory disease of the airways characterized by symptoms such as wheezing, shortness of breath, chest tightness and coughing. It is a global public health issue with an etiology that remains incompletely understood. The diagnosis of asthma is based on a detailed medical history and evidence of hyperreactivity. The treatment of asthma is based on a combination of pharmacological and non-pharmacological methods. Pharmacological methods include various classes of drugs, such as inhaled corticosteroids (ICS), beta-agonists, muscarinic antagonists, leukotriene receptor antagonists, methylxanthines, mast cell stabilizers and biological therapies. Each of these classes has a specific mechanism of action and is used depending on the severity and specific characteristics of asthma in individual patients. A stepwise approach to asthma treatment recommends adjusting therapy based on disease severity and control. Mild and moderate asthma can be treated with a combination of ICS and long-acting beta-agonists (LABA). Severe asthma requires high doses of medication or additional therapies to achieve adequate control. Non-pharmacological treatment includes strategies such as avoiding asthma triggers, regular physical activity and weight management. Patient education on the proper use of inhalers, recognizing symptoms and managing triggers is crucial for the long-term success of therapy. The treatment of asthma also carries certain complications. For example, ICS can lead to the development of oral candidiasis, dysphonia and coughing, while beta-agonists can cause tachycardia and tremors. Oral corticosteroids have the most adverse effects, with long-term use negatively impacting the skin, eyes, immune, musculoskeletal and cardiovascular system
Personalized treatment of cardiovascular diseases with the help of pharmacogene analysis
Kardiovaskularne bolesti su globalno vodeći uzrok smrti. One se liječe primjenom brojnih lijekova iz raznih skupina. S obzirom na postojanje razlika među pojedincima u odgovorima na lijekove, u terapiji ovih bolesti je potreban precizan i učinkovit pristup. Farmakogenomika, koja proučava utjecaj genskih varijacija na odgovore bolesnika na lijek, donosi značajan napredak u personalizaciji terapije. U ovom preglednom radu analiziraju se važni farmakogeni koji utječu na farmakodinamiku i farmakokinetiku lijekova s djelovanjem na kardiovaskularni sustav. To uključuje pregled polimorfizama membranskih prijenosnika i enzima zaduženih za biotransformaciju lijekova. Primjeri enzima čiji se geni analiziraju su CYP2C9, CYP2C19 i CYP2D6. Njihovi aleli se mogu fenotipski razlikovati s obzirom na razinu enzimske aktivnosti, prema čemu se osobe konačno svrstavaju između sporog i vrlo brzog metabolizatora. Membranski prijenosnici također mogu imati promijenjenu transportnu funkciju zbog varijacija u genima, od kojih su SLCO1B1 i ABCG2 važni kod primjene statina. Zbog ovih razlika pacijenti mogu biti izloženi višim ili manjim količinama lijekova nego što je potrebno i posljedično imati neželjene nuspojave ili smanjen terapijski učinak. Društva kao što su CPIC i DPWG stoga daju kliničarima preporuke o odabiru terapije i doziranju ovisno o genotipu/fenotipu pacijenta.Cardiovascular diseases are the leading cause of death globally. They are treated with numerous drugs from various classes. Given the differences among individuals in drug responses, a precise and effective approach is needed in the therapy of these diseases. Pharmacogenomics studies genetic variations that influence drug responses, advancing personalized therapy. This review paper analyzes important pharmacogenes that affect the pharmacodynamics and pharmacokinetics of drugs acting on the cardiovascular system. It includes a review of polymorphisms of membrane transporters and enzymes responsible for drug biotransformation. Examples of enzymes whose genes are analyzed include CYP2C9, CYP2C19, and CYP2D6. Their alleles can differ phenotypically regarding the level of enzymatic activity, categorizing individuals as slow to ultra-rapid metabolizers. Membrane transporters can also have altered transport functions due to gene variations, with SLCO1B1 and ABCG2 being important in the use of statins. Due to these differences, patients may be exposed to higher or lower amounts of drugs than necessary, resulting in unwanted side effects or reduced therapeutic efficacy. Groups such as CPIC and DPWG provide clinicians with recommendations on therapy selection and dosing based on the patient's genotype/phenotype
Slabo diferencirani, inzularni, karcinom štitnjače
Slabo diferencirani (inzularni) karcinom štitnjače predstavlja heterogenu skupinu karcinoma, s varijabilnim ponašanjem, kliničkim tijekom i ishodom bolesti. Javlja se u 2 – 15% slučajeva svih karcinoma štitnjače, obično u starijoj životnoj dobi i češće u žena. Zbog svoje heterogene građe, za dijagnostiku karcinoma su 2006. godine predloženi Torinski kriteriji koji obuhvaćaju prisutnost solidne, trabekularne ili inzularne građe, odsutnost klasičnih nuklearnih obilježja papilarnog karcinoma, prisutnost jedne od agresivnijih obilježja karcinoma (atipične jezgre, povećana mitotička aktivnost tumorskih stanica te tumorska nekroza). Tumor se prezentira kao naglo rastući, bezbolan čvor na vratu, a mogu se javiti i nespecifični simptomi lokalne invazije u obliku dispneje, disfagije i promuklosti. Širi se limfogeno u regionalne limfne čvorove vrata, kao i hematogeno u pluća i kosti. U dijagnostici tumora koristi se ultrazvuk uz pridruženu citološku punkciju, histološka analiza tumorskog tkiva, dok se slikovne metode koriste za procjenu proširenosti bolesti i terapijskog pristupa. Kao terapijske opcije ističu se kirurško liječenje u vidu totalne tiroidektomije s pridruženom disekcijom vratnih limfnih čvorova, radiojodna terapija, terapija vanjskim snopom zračenja, ali i ciljana terapija upotrebom inhibitora tirozin kinaze. Tumor ima lošu prognozu, s petogodišnjim preživljenjem u 50% slučajeva i sklonosti recidivima.Poorly differentiated thyroid cancer or insular cancer represents a heterogeneous group of cancers with variable behavior, clinical course and disease outcome. It occurs in 2 – 15% of all thyroid cancer cases, usually in older people and more often in females. Due to its heterogeneous structure, the Turin criteria were proposed in order to diagnose the cancer, which include the presence of either solid, trabecular or insular structure, the absence of nuclear features seen in papillary carcinoma and the presence of one or more aggressive features of cancer (atypical nuclei, increased mitotic activity of tumor cells, tumor necrosis). The tumor presents as a rapidly growing, painless neck nodule, and non-specific symptoms of local invasion, such as dyspnea, dysphagia and hoarseness may also occur. It spreads lymphogenously to the regional lymph nodes of the neck, as well as hematogenously to the lungs and bones. In the diagnosis of tumors, ultrasound with associated cytological aspiration is used along with hystological analysis of tumor tissue, while imaging methods are used to assess the extent of the disease and the therapeutic approach. Surgical treatment consisted of total thyroidectomy with associated cervical lymph node dissection is used as a first line of treatment, as well as radioiodine therapy, external beam therapy and targeted therapy using tyrosine kinase inhibitors. The tumor has a poor prognosis, with five-year survival in 50% of cases and a high tendency to relapse
Surgical approaches and techniques of nephrectomy
Nefrektomija, kirurški postupak uklanjanja bubrega, kirurški je zahvat koji se razvijao od prvih fizioloških eksperimenata na životinjama do današnjih rutinskih uroloških operacija koje se izvode zbog različitih indikacija, od kojih su najčešći maligni tumori bubrega, ponajprije karcinomi. Osim malignih oboljenja, u razloge potreba za uklanjanjem bubrega ubrajaju se infekcije bubrežnog tkiva, ozljede i sva oboljenja bubrežnog parenhima koja organizmu predstavljaju dodatno opterećenje, poglavito kardiovaskularno. Međutim, osim uklanjanja bubrega zbog patoloških procesa, za potrebe bubrežne transplantacije moguće je kirurški uklanjati i zdrave bubrege iz neoboljelih pojedinaca. Bubrezi se operativno mogu ukloniti u potpunosti, u obliku radikalne ili jednostavne nefrektomije, ili se uklanjaju samo djelomično, u obliku parcijalne nefrektomije, odnosno operacije koja štedi nefrone. Kirurški se bubregu za uklanjanje može pristupiti transperitonealno, kada se to postiže prednjim rezovima, odnosno laparoskopijom kroz troakare postavljene na prednjoj trbušnoj stijenci ili se pristupa retroperitonealno, bočnim rezovima ili retroperitoneoskopijom kroz troakare postavljene na stražnjoj i bočnoj stijenci. Osim tradicionalnih otvorenih operacija i minimalno invazivne laparoskopije i njenih modifikacija, nefrektomije se sve češće provode potpomognute robotskim sustavima, što je pogotovo korisno za izvođenje minimalno invazivnih parcijalnih nefrektomija. Kao jedan od najsuvremenijih pristupa i načina izvođenja nefrektomije spominje se transluminalna endoskopska nefrektomija kroz prirodne otvore. Svaki naveden pristup i tehnika praćeni su vlastitim prednostima i manama, ali prilikom odabira načina provođenja operacije velik doprinos imaju i iskustvo operatera te opremljenost ustanove.Nephrectomy, the surgical procedure for removing a kidney, has evolved from earliest physiological experiments on animals to today's routine urological operations performed for various indications, the most common being malignant kidney tumors, primarily carcinomas. In addition to malignant diseases, reasons for needing a kidney removal include infections of renal tissue, injuries and every disease of the renal parenchyma that poses an additional burden to the body, especially cardiovascular. However, apart from kidney removal due to pathological processes, healthy kidneys from non-diseased individuals can also be surgically removed for the purposes of kidney transplantation. Kidneys can be surgically removed completely, in the form of radical or simple nephrectomy, or only partially, in the form of partial nephrectomy, also known as nephron-sparing surgery. Surgical access to the kidney for removal can be achieved transperitoneally, through anterior incisions or laparoscopically via trocars placed on the anterior abdominal wall, or retroperitoneally, through flank incisions or retroperitoneoscopically via trocars placed on the posterior and lateral walls. In addition to traditional open surgery and minimally invasive laparoscopy and its modifications, nephrectomies are increasingly performed with the assistance of robotic systems, which is especially useful for performing minimally invasive partial nephrectomy. One of the most advanced contemporary approaches and methods for performing nephrectomy is transluminal endoscopic nephrectomy through natural orifices. Each of these approaches and techniques comes with its own advantages and disadvantages, but the experience of the performing surgeon, as well as the available equipment of the healthcare institution also play a significant role in the choice of surgical method
Endoscopic management of complications in acute pancreatitis
U lokalne komplikacije akutnog pankreatitisa ubrajaju se akutna peripankreatična tekuća kolekcija, pseudocista gušterače, akutna nekrotična kolekcija i kasna ozidana nekroza (WON). Pseudocista i kasna ozidana nekroza kronične su komplikacije i, ako su simptomatske, zahtijevaju intervenciju. Endoskopska transluminalna drenaža uključuje formiranje kanala između gastrointestinalnog sustava i lumena kolekcije endoskopskim putem te postavljanje potpornice (stenta). Metalni samoekspandirajući stentovi (engl. LAMS – lumen apposing metal stents) postaju sve rašireniji u kliničkoj praksi i u velikoj mjeri zamjenjuju plastične stentove. Endoskopska transluminalna nekrozektomija sljedeći je korak u endoskopskoj intervenciji ukoliko drenaža nije dostatna za rezoluciju kolekcije.
U ovoj retrospektivnoj studiji usporedili smo ishode liječenja pacijenata s kroničnim peripankreatičnim kolekcijama liječenih endoskopski ugradnjom LAMS-a na Zavodu za gastroenterologiju i hepatologiju Klinike za unutarnje bolesti KBC-a Sestre milosrdnice u periodu od studenoga 2016. do studenoga 2023. godine. U tom periodu liječena su 52 bolesnika, od čega 62% muških i 38% ženskih. Prosječna dob ispitanika bila je 57,7 ± 11,9 godina. U 49 (94%) slučajeva bilo je riječ o WON-ovima, dok su preostali bili pankreatične pseudociste (6%). Etiologija pankreatitisa većinski je bila bilijarna (87%). Tehnički uspjeh procedure bio je 100%, uz klinički uspjeh od 96%. Od 52 ispitanika uključena u analizu, samo je 6% imalo značajne komplikacije zahvata, uz dva smrtna slučaja. Bolesnici su imali značajan pad tjelesne mase, ali bez pada skeletne mišićne mase. Sarkopeniju je imalo 27% bolesnika i prije i nakon endoskopskog liječenja što je pokazalo da sarkopenija uistinu nastaje u ovoj bolesti, ali i da se može spriječiti njeno pogoršanje ili uopće razvoj adekvatnim liječenjem i nutritivnom intervencijom, posebice visokim dnevnim unosom proteina.Local complications of acute pancreatitis include acute peripancreatic liquid collection, pancreatic pseudocyst, acute necrotic collection, and walled-off necrosis (WON). Pseudocyst and walled-off necrosis are considered chronic complications and are treated invasively in case of being symptomatic. Endoscopic transluminal drainage involves the formation of a channel between the gastrointestinal system and the lumen of the collection and placement of a stent. Lumen-apposing metal stents (LAMS) are becoming more widespread in practice and are widely replacing plastic stents. Endoscopic transluminal necrosectomy is the next step in endoscopic intervention if drainage is not sufficient to resolve the collection.
In this study, we compared the treatment outcomes of patients with chronic peripancreatic collections treated endoscopically by implantation of LAMS at the Department of Gastroenterology and Hepatology, Department for Internal Diseases, University Hospital Center “Sestre Milosrdnice” in the period from November 2016 to November 2023. 52 patients were treated in that period, of which 62% were male and 38% were female. The average age of the subjects was 57.7 ± 11.9 years. In 49 (94%) cases, the collections were WONs, while the remaining were pancreatic pseudocysts (6%). The etiology of pancreatitis was mostly biliary (87%). The technical success of the procedure was 100% and the clinical success was 96%. Of the 52 patients included in the analysis, significant complications of the procedure were observed in only 6% of the patients along with two cases of death. Patients suffered from a significant decrease in body mass during treatment, but no decrease in skeletal muscle mass was observed. 27% of patients had sarcopenia both before and after the endoscopic treatment, which showed that sarcopenia indeed occurs in this condition, but also that it can be prevented from worsening or even developing by adequate treatment and nutritional intervention, especially by high protein intake
Clinical value of episignature analysis in neurodevelopmental disorders
Neurorazvojni poremećaji skupina su poremećaja s teškoćama u osobnom, socijalnom,
akademskom i/ili okupacijskom funkcioniranju, a za sve više njih se otkriva povezanost s
promjenama u epigenomu pojedinca koje potom utječu na fenotip. Općenito, epigenetički
mehanizmi omogućuju da se više različitih fenotipa ispolji kao produkt jednog genotipa. Promjena
u metilaciji DNA pa tako i aktivnosti gena, dovodi se u vezu s nastankom raka i mnogih drugih
bolesti. Epigenetički potpis uključuje, između ostalog, skup diferencijalno metiliranih citozina i
specifičan je za točno određenu stanicu. Specifičan je s obzirom na tkivo, dob te prisutnu
patologiju. Analiza obrasca metilacije DNA, odnosno epigenetičkog potpisa, može neizravno
ukazati na promjene u ekspresiji raznih gena i promjene u efikasnosti raznih enzima i ostalih
proteina uključenih u proces metilacije, te tako, bez sekvenciranja same patološke varijante, točno
ukazati na njenu prisutnost i efekt. Kod velikog broja rijetkih neurorazvojnih poremećaja
zamijećena je podliježuća patološka varijanta gena uključenih u proces metilacije DNA. Analiza
metilacije DNA kvantificira stupanj metilacije DNA, te točno određuje koji CpGovi su metilirani
ili nemetilirani. Dosadašnjim analizama epigenetički potpis je definiran za mnoge rijetke
neurorazvojne poremećaje. Uspoređivanje epigenetičkog potpisa nedijagnosticiranih pacijenata s
definiranim potpisima može pomoći postavljanju kliničke dijagnoze. Stoga se počeo koristiti u
klasifikaciji varijanti nejasnog značaja i inicijalnom postavljanu dijagnoze, a potencijalno i kao
metoda ranog probira, identifikacije mogućih meta za razvoj novih lijekova i korak ka
personaliziranoj medicini.Neurodevelopmental disorders are a group of disorders with difficulties in personal, social,
academic and/or occupational functioning, and for more and more of them, a connection with
changes in the epigenome of the individual is being discovered, which then affects the phenotype.
In general, epigenetic mechanisms allow multiple different phenotypes to manifest as a product of
a single genotype. Changes in methylation, and thus gene activity, are linked to the development
of cancer and many other diseases. The epigenetic signature includes a set of differentially
methylated cytosines specific to a particular cell. It is specific with respect to tissue, age, and the
presence of pathology. Analysis of DNA methylation levels, or the epigenetic signature, can
indirectly indicate changes in the expression of various genes and changes in the efficiency of
various enzymes and proteins involved in the methylation process, and in this way, without
sequencing the pathological variant itself, accurately indicate its presence and effect. In a large
number of rare neurodevelopmental disorders, an underlying pathological variant of genes
involved in the methylation process has been observed. Methylation analysis quantifies the degree
of methylation and precisely determines which CpGs are methylated or unmethylated. Previous
analyses have defined the epigenetic signature for many rare neurodevelopmental disorders.
Comparison of the epigenetic signature of undiagnosed patients with defined signatures can help
establish a clinical diagnosis. Thus, it has started to be used in the classification of variants of
uncertain significance (VUS) and initial diagnosis. Also, potentially, as a method for early
screening, identification of possible targets for the development of new drugs, and a step towards
personalized medicine