Veterinary medicine - Repository of PHD, master's thesis
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Immunotherapy in lung cancer treatment
Karcinom pluća je drugi po učestalosti sijela karcinoma kod muškaraca, te treći kod
žena u Republici Hrvatskoj, dok u nekim zemljama zauzima i visoko prvo mjesto. U
većini slučajeva otkriva se u poodmaklim stadijima bolesti kada su terapijske
mogućnosti ograničene. Uz daljne tehnološko napredovanje konvencionalnih
dijagnostičkih metoda, nužno je identificirati biomarkere koji bi potencijalno imali ulogu u
ranoj dijagnostici, te predikciji razvoja i progresije karcinoma. Tradicionalni pristupi
liječenju, uključujući kirurgiju, kemoterapiju i radioterapiju, i dalje imaju važnu ulogu,
međutim sami po sebi ne daju zadovoljavajuće rezultate u liječenju karcinoma pluća.
Imunoterapija je inovativna terapijska opcija tumora koja je i dalje u svojim začecima, a
za cilj ima potaknuti (ili ponovno potaknuti) stanični imunološki odgovor. Nedavni
tehnički napreci pridonijeli su boljem razumijevanju imunogenosti karcinoma pluća, a od
tada su se razvile različite vrste imunoterapija poput terapijskog cjepiva,
imunomodulatora, adoptivne stanične terapije te monoklonskih protutijela. Blokatori
imunoloških kontrolnih točaka trenutno imaju najveću ulogu u terapiji karcinoma pluća,
međutim, daljnja istraživanja nastoje riješiti izazove koje sa sobom donose nova
saznanja u polju imunoterapije, te omogućiti i ostale vrste imunoterapije dostupnima
široj skupini pacijenata.Lung cancer is the second most common cancer site among men and the third among
women in the Republic of Croatia, while in some countries it even ranks first. In most
cases, it is diagnosed at advanced stages of the disease when treatment options are
limited. Along with the continued technological advancement of conventional diagnostic
methods, it is essential to identify biomarkers that could potentially play a role in early
diagnosis and in predicting the development and progression of cancer. Traditional
treatment approaches, including surgery, chemotherapy, and radiotherapy, still play an
important role; however, on their own, they do not yield satisfactory results in the
treatment of lung cancer. Immunotherapy is an innovative cancer treatment option that
is still in its infancy, aiming to stimulate (or re-stimulate) the cellular immune response.
Recent technical advances have contributed to a better understanding of the
immunogenicity of lung cancer, leading to the development of various types of
immunotherapy such as therapeutic vaccines, immunomodulators, adoptive cell
therapy, and monoclonal antibodies. Immune check point inhibitors currently play the
most significant role in lung cancer therapy; however, ongoing research aims to address
the challenges brought by new insights in the field of immunotherapy and to make other
types of immunotherapy accessible to a broader group of patients
Effectiveness of Treating Patients with Atherosclerotic Disease Using PCSK9 Inhibitors in Real-World Settings
Ateroskleroza je kronična bolest arterijske stijenke i vodeći uzrok smrtnosti u zapadnim zemljama. Temelj prevencije i liječenja KV bolesti predstavlja snižavanje razine LDL kolesterola u plazmi. U bolesnika kod kojih se unatoč primjeni statina i ezetimiba ne postižu ciljne vrijednosti LDL-a, kliničke smjernice preporučaju primjenu PCSK9 inhibitora.
Cilj ovog istraživanja bio je ispitati učinkovitost i sigurnost trojne antilipidne terapije koja uključuje maksimalnu podnošljivu dozu statina, ezetimib te jedan od triju dostupnih PCSK9 inhibitora (evolokumab, alirokumab, inklisiran) na vrijednosti LDL kolesterola u stvarnim kliničkim uvjetima u bolesnika s familijarnom hiperlipoproteinemijom i aterosklerozom, te u bolesnika s akutnim koronarnim sindromom, uz analizu čimbenika koji mogu utjecati na terapijski ishod. Retrospektivno su analizirani podaci iz bolničkog informacijskog sustava 106 bolesnika liječenih PCSK9 inhibitorima u KBC Sestre milosrdnice. Za ispitanike su prikupljeni: osnovni demografski podaci, indikacija za primjenu PCSK9 inhibitora, vrijednosti LDL kolesterola prije i nakon terapije, prethodna terapija, vrsta korištenog PCSK9 inhibitora, redovitost primjene terapije i razlozi neredovitog uzimanja lijeka. Zabilježeno je značajno sniženje LDL kolesterola, s početnog medijana od 3,4 mmol/L na 1,35 mmol/L nakon minimalno tri mjeseca liječenja (P < 0,001). Nije utvrđena razlika u učinkovitosti između muškaraca i žena. Redovita primjena terapije povezana je sa značajno nižim vrijednostima LDL-a. Najčešći razlozi neredovite primjene bili su: osobni razlozi (adherencija), administrativni problemi i nuspojave.
PCSK9 inhibitori, u kombinaciji sa statinom i ezetimibom, pokazuju visoku učinkovitost u snižavanju LDL kolesterola u uvjetima svakodnevne kliničke prakse. Uspjeh terapije uvelike ovisi o adherenciji, što ukazuje na važnost sustavne kontrole i potpore bolesnicima.Atherosclerosis is a chronic disease of the arterial wall and a leading cause of death in Western countries. The cornerstone of prevention and treatment of cardiovascular disease is the reduction of plasma LDL cholesterol levels. In patients who do not achieve LDL target values despite the use of statins and ezetimibe, clinical guidelines recommend the use of PCSK9 inhibitors.
This study aimed to examine the efficacy and safety of triple antilipid therapy that includes the maximum tolerated dose of a statin, ezetimibe, and one of the three available PCSK9 inhibitors (evolocumab, alirocumab, inclisiran) on LDL cholesterol levels in real-world clinical settings in patients with familial hyperlipoproteinemia and atherosclerosis, and in patients with acute coronary syndrome, with an analysis of factors that may influence therapeutic outcome. Data from the hospital information system of 106 patients treated with PCSK9 inhibitors at KBC Sestre Milosrdnice were retrospectively analyzed. The following data were collected for the subjects: basic demographic data, indication for PCSK9 inhibitor use, LDL cholesterol levels before and after therapy, previous therapy, type of PCSK9 inhibitor used, regularity of therapy, and reasons for irregular drug use. A significant reduction in LDL cholesterol was recorded, from an initial median of 3.4 mmol/L to 1.35 mmol/L after a minimum of three months of treatment (P < 0.001). No difference in efficacy was found between men and women. Regular use of therapy was associated with significantly lower LDL values. The most common reasons for non-regular use were: personal reasons (adherence), administrative problems, and side effects.
PCSK9 inhibitors, in combination with statins and ezetimibe, show high efficacy in lowering LDL cholesterol in everyday clinical practice. The success of therapy largely depends on adherence, which indicates the importance of systematic monitoring and support for patients
Ventilator-associated pneumonia
Pneumonija povezana s mehaničkom ventilacijom (VAP) je bolnička infektivna bolest pluća koja se razvija u bolesnika nakon najmanje 48 sati invazivne mehaničke ventilacije, obično u jedinicama intenzivne skrbi. VAP je jedna od najčešćih bolničkih infekcija, a incidencija i ishod znatno variraju ovisno o demografskim obilježjima bolesnika, lokalnoj epidemiologiji i razini kvalitete skrbi. Najveći rizik bilježe starije osobe s kroničnim bolestima, ali su i djeca, osobito nedonoščad, također podložna razvoju ove infekcije. VAP najčešće uzrokuju Gram-negativne bakterije poput Pseudomonas aeruginosa, Acinetobacter baumannii i Klebsiella pneumoniae, iako uzročnici mogu biti i Gram-pozitivne bakterije, virusi i gljive, osobito kod imunokompromitiranih bolesnika. Razvoj VAP-a je složen i uključuje narušavanje prirodnih obrambenih mehanizama dišnog sustava mehaničkom ventilacijom, kolonizaciju i stvaranje biofilma na endotrahealnim tubusima, ponavljajuću mikroaspiraciju te promjene plućnog mikrobioma. Važne čimbenike rizika predstavljaju trajanje ventilacije, sedacija, invazivni zahvati, malnutricija, pušenje i prekomjerna konzumacija alkohola. Nespecifična klinička slika često se preklapa s drugim stanjima, što otežava rano prepoznavanje bolesti. Dijagnoza se temeljeni na kliničkoj sumnji, slikovnoj dijagnozi novih ili progresivnih plućnih infiltrata i identifikaciji uzročnog mikroorganizma iz respiratornih uzoraka. Liječenje se započinje odmah primjenom empirijske antimikrobne terapije širokog spektra, koja se kasnije prilagođava prema mikrobiološkim nalazima i lokalnim obrascima rezistencije. Potporna terapija uključuje zaštitnu ventilaciju i mjere kontrole infekcije. Prevencija se temelji na mjerama poput podizanja uzglavlja, oralne higijene i smanjenja trajanja mehaničke ventilacije. Unatoč napretku u prevenciji i liječenju, VAP i dalje predstavlja velik izazov u intenzivnoj medicini. Daljnja istraživanja i multidisciplinarni pristup ključni su u smanjenju incidencije i poboljšanju ishoda liječenja.Ventilator-associated pneumonia (VAP) is a hospital-acquired lung infection that develops in patients after at least 48 hours of invasive mechanical ventilation, typically occurring in intensive care units. VAP is one of the most prevalent hospital infections, with incidence and outcomes varying greatly depending on patient demographics, local epidemiology, and quality of care. The highest risk is seen in older adults with chronic illnesses, but children, especially premature infants, are also vulnerable. VAP is most often caused by Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, though Gram-positive bacteria, viruses, and fungi can also be involved, particularly in immunocompromised patients. The development of VAP is complex and involves multiple mechanisms, including disruption of the body’s natural airway defenses by mechanical ventilation, bacterial colonization and biofilm formation on endotracheal tubes, recurrent microaspiration, and alterations in the lung microbiome. Notable risk factors include duration of ventilation, sedation, invasive procedures, malnutrition, and factors like smoking and alcohol abuse. The clinical presentation is often subtle and overlaps with other conditions, making early diagnosis challenging. Diagnosis is based on a combination of clinical suspicion, imaging methods to detect new or progressive lung infiltrates, and identification of the causative organism from respiratory samples. Treatment begins immediately with broad- spectrum antibiotics, which are later adjusted based on microbiology results and local resistance patterns. Supportive care includes protective ventilation and infection control. Prevention is based on measures such as head elevation, oral hygiene, and reduced ventilation duration. Despite advances in prevention and treatment, VAP remains a major challenge in intensive care medicine. Continued research and a multidisciplinary approach are key to reducing its incidence and improving patient outcomes
Impact of the 10-valent pneumococcal conjugate vaccine (PCV10) on pneumococcal carriage in healthy children and children with acute otitis media and pneumonia: emergence of serotypes 3, 6C and 19A in Croatia
Background: In 2019, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Croatian immunization programme, a first for this European PCV-naïve country. This study aimed to evaluate the impact of PCV10 on pneumococcal serotype distribution among asymptomatic children and children with pneumonia and/or acute otitis media.
Methods: Cross-sectional studies were conducted before and after the PCV10 introduction, with nasopharyngeal swabs collected from 1500 healthy children under 48 months of age. An additional 324 children under 18 years with pneumonia and/or acute otitis media, from whom Streptococcus pneumoniae was isolated, were also included. Isolates were identified by conventional methods, serotyped by Quellung reaction, and tested for antimicrobial susceptibility using disk diffusion and gradient test methods. We report prevalence, absolute risk (prevalence) difference (RD) and relative risk (prevalence) ratio (RR) differences between exposed and control children.
Results: Carriage prevalence among healthy children increased from 19.9% to 28.7%, primarily due to a rise in non-vaccine serotypes (NVT). Adjusted probabilities for serotypes 6C (RR 3.18; 95% CI, 1.43-7.06), 11A (RR 2.8; 95% CI, 1.22-6.39), 19A (RR 4.18; 95% CI, 1.18-14.9) and 23A (RR 3.93; 95% CI, 1.87-8.24) were significantly higher in healthy exposed children. Prevalences of these serotypes were also higher in exposed children with pneumonia/acute otitis media. In this cohort, serotype 3 increased (RR 4.6; 95% CI, 2.02-10.3), becoming the leading post-PCV10 isolate in the overall studied population. Serotypes 3 and 19A were almost entirely responsible for complicated pneumonia cases for which the probability increased by 21-fold. Antimicrobial susceptibility remained similar across periods.
Conclusions: In the early post-vaccine period significant increase of PCV10 vaccine-related serotypes (6C, 19A) was observed. Continued monitoring is also essential due to concerning rise of serotype 3 in patients with mucosal infections and a higher risk for complicated pneumonia
Microbial agents isolated in spontaneous bacterial peritonitis at the University Hospital Center Sestre milosrdnice
Spontani bakterijski peritonitis (SBP) predstavlja jednu od najčešćih i najozbiljnijih infekcija u bolesnika s dekompenziranom cirozom jetre i ascitesom. Iako su dijagnostičke i terapijske mogućnosti značajno napredovale, SBP i dalje nosi visoku stopu smrtnosti. Cilj ovog rada bio je analizirati mikrobiološke uzročnike SBP-a u pacijenata liječenih u Kliničkom bolničkom centru Sestre milosrdnice, s posebnim naglaskom na učestalost i obrasce antimikrobne rezistencije, kako bi se temeljem dobivenih rezultata procijenila prikladnost sadašnje empirijske antibiotske terapije. U retrospektivno istraživanje uključeno je 19 bolesnika s dijagnozom ciroze jetre kod kojih je mikrobiološkom analizom izoliran uzročnik iz ascitesne tekućine, uz kliničku i laboratorijsku potvrdu SBP-a. Najčešći izolirani uzročnici bili su Escherichia coli (uključujući sojeve koji luče beta-laktamazu) te Streptococcus viridans. Analizom je utvrđena podjednaka učestalost Gram-negativnih i Gram-pozitivnih mikroorganizama, koja se suprotstavlja dosadadašnjem mišljenju o dominantnoj zastupljenosti Gram-negativnih bakterija. Također, uočena je značajna učestalost multirezistentnih organizama, posebice u infekcijama stečenim u bolničkom okruženju ili povezanim sa zdravstvenom skrbi. Empirijska antibiotska terapija najčešće je podrazumijevala primjenu ceftriaksona, cefalosporinskog antibiotika 3. generacije, u skladu s važećim nacionalnim i europskim smjernicama. Međutim, u gotovo polovini slučajeva terapija je bila korigirana zbog mikrobiološke potvrde rezistencije, najčešće uvođenjem meropenema ili kombinacije piperacilina/tazobaktama. Rezultati ukazuju na potrebu redefiniranja empirijskog terapijskog pristupa, osobito u populaciji s većim rizikom za infekcije multirezistentnim patogenima. Antibiotici poput piperacilina/tazobaktama i meropenema pokazali su bolju učinkovitost te bi mogli predstavljati primarnu terapijsku opciju u bolesnika s nozokomijalnim ili SBP-om povezanim s korištenjem zdravstvenog sustava. Pravovremeno započinjanje djelotvorne antibiotske terapije, uvođenje ciljane terapije temeljene na ranom mikrobiološkom testiranju, praćenje lokalnih obrazaca rezistencije i racionalna uporaba antibiotika ključni su za poboljšanje ishoda liječenja u ovoj visoko rizičnoj skupini bolesnika.Spontaneous bacterial peritonitis (SBP) is one of the most common and severe infections in patients with decompensated liver cirrhosis and ascites. Despite significant advances in diagnostic and therapeutic options, mortality rates related to SBP still remain high. This study aimed to analyze microbial pathogens causing SBP in patients treated at the University Hospital Centre Sestre milosrdnice, with a focus on the prevalence and patterns of antimicrobial resistance,to assess the efficacy and optimize current empirical antibiotic therapy. This retrospective study included 19 patients with liver cirrhosis in whom a microbial pathogen was cultured from ascitic fluid during hospitalization, with clinical and laboratory confirmation of spontaneous bacterial peritonitis (SBP). The most frequently isolated pathogens were Escherichia coli (including beta-lactamase producing strains) and Streptococcus viridans, with a similar proportion of Gram-negative and Gram-positive bacteria. This contrasts with previous assumptions of Gram-negative predominance. A significant proportion of multidrug-resistant organisms was also observed, especially in hospital-acquired or healthcare-associated infections. Empirical antibiotic therapy was most commonly initiated with ceftriaxone, a third-generation cephalosporin, following current national and European guidelines. However, in nearly half of the cases, therapy had to be adjusted due to confirmed resistance, most often with the introduction of meropenem or piperacillin/tazobactam. The findings highlight the need to redefine the empirical treatment approach, particularly in populations at a higher risk of infection with multidrug-resistant bacteria. Antibiotics such as piperacillin/tazobactam and meropenem showed better efficacy and may represent more appropriate first-line options in patients with nosocomial or healthcare-associated SBP. Timely antibiotic treatment, implementation of targeted therapy based on early microbiological testing, monitoring of local resistance patterns, and rational antibiotic use are crucial steps in improving treatment outcomes in this high-risk patient group
Each Indicator of Socioeconomic Status (Education, Occupation, Income, and Household Size) Is Differently Associated with Children’s Diets: Results from a Cross-Sectional CroCOSI Study
Background: There has yet to be an agreement on which specific socioeconomic status (SES) indicator most effectively reflects disparities in children’s diets. However, children from lower SES backgrounds are particularly vulnerable, as research in other countries indicates that their diets contain fewer fruits and vegetables and more sweetened beverages. This paper aims to evaluate the associations between dietary habits and various SES indicators (education, occupation, income, and household size) among a representative sample of children in Croatia aged 7–10.
Methods: Parents of children were asked to complete a questionnaire that contained indicators of their children’s dietary habits and socioeconomic status (n = 5608). Associations between SES and children’s dietary habits were assessed using logistic regression models.
Results: The mother and father’s educational attainment were strongly positively associated with breakfast consumption. Children of parents with a lower educational level consumed sweetened beverages, sweet snacks, and fast food slightly more often than children in families with a higher educational background. The mother’s education was inversely associated with vegetable and cereal consumption, while the father’s education was inversely associated with fruit and bakery product consumption. Meanwhile, household income per unit had a significant influence on the consumption of soft drinks and bakery products. Household size had a significant influence solely on sweet snack consumption.
Conclusions: Each SES indicator showed an independent association with at least one particular dietary habit, except for the parent’s employment status
The role of ubiquitin C-terminal hydrolase (UCH-L1) and protein S100B in differentiating patients with epileptic and psychogenic non-epileptic seizures - Pilot study
Objective: Psychogenic non-epileptic seizures (PNES) are functional neurological disorders that are often misdiagnosed and treated as epileptic seizures (ES). Video-electroencephalography (v-EEG) is the gold standard for differentiating ES from PNES. However, blood biomarkers provide a faster and more accessible methodology, particularly for unwitnessed events. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and protein S100B are key biomarkers released following neuronal and glial damage. Previous experimental and clinical studies have shown increased postictal serum and cerebrospinal fluid (CSF) levels of UCH-L1 and S100B in patients with ES.
Methods: This prospective cohort pilot study compared postictal serum levels of UCH-L1 and S100B proteins in subjects with ES to those with PNES, aiming to identify specific biomarkers for distinguishing these conditions. To exclude confounding factors, the inclusion criteria required normal magnetic resonance (MR) findings of the brain. Strict timing of blood sampling and v-EEG monitoring were used for diagnosing PNES. The study included 32 subjects with epilepsy, 36 with PNES, and 30 healthy controls.
Results: A significant difference in postictal UCH-L1 levels was observed among the groups. Subjects with ES had significantly higher postictal UCH-L1 levels (pg/mL) compared to those with PNES (p = 0.049) and healthy controls (p = 0.029). No significant differences were found between PNES subjects and healthy controls (p = 0.756). Postictal protein S100B levels did not differ significantly between the groups (p = 0.515).
Significance: This study confirms the potential of postictal UCH-L1 levels as a biomarker for distinguishing ES from PNES. However, it also raises questions about the utility of protein S100B as a biomarker in epilepsy. Given the pilot nature of this study, UCH-L1 cannot yet be adopted for clinical use due to the small sample size, as statistical significance may have been driven by a subset of eight patients.
Plain language summary: This study evaluated two potential biomarkers, UCH-L1 and S100B, to differentiate ES from PNES in clinical practice. Our findings showed elevated postictal UCH-L1 levels in subjects with epilepsy compared to those with PNES, while no significant differences in S100B levels were observed among the groups
Cutaneous manifestations of lupus erythematosus
Eritemski lupus je kronična autoimuna bolest vezivnog tkiva koja može zahvatiti gotovo sve organske sustave, među kojima je koža drugi najčešće zahvaćeni organ. Iako kožne manifestacije mogu biti izolirane, bez zahvaćanja unutarnjih organa, javljaju se u čak 80% bolesnika sa sistemskim eritemskim lupusom a u četvrtine bolesnika kao prvi znak bolesti. Patogeneza kutanog eritemskog lupusa je kompleksna i multifaktorijalna. Uključuje genetsku predispoziciju, epigenetske promjene i vanjske čimbenike, pri čemu se najviše ističe ultraljubičasto zračenje. Ključnu ulogu ima prekomjerna ekspresija interferona I, koja pokreće samoamplificirajuću upalnu petlju između urođene i stanične imunosti. Prva široko prihvaćena klasifikacija CLE-a je Gilliamova klasifikacija iz 1981. godine, koja dijeli lezije na lupus- specifične i lupus-nespecifične. LE-specifične lezije karakterizira prisutnost histološkog nalaza tzv. interface dermatitisa, a obuhvaćaju akutni, subakutni i kronični oblik. S ciljem preciznijeg razlikovanja pojedinih podtipova, Düsseldorfska klasifikacija iz 2004. godine proširuje Gilliamovu podjelu uvođenjem intermitentnog kutanog eritemskog lupusa kao četvrtog oblika, koji uključuje eritemski lupus tumidus. Dijagnoza kutanog eritemskog lupusa temelji se na kliničkoj slici, patohistološkim značajkama, serološkom profilu te direktnoj imunoflorescenciji. Unatoč značajnom utjecaju na kvalitetu života, terapijske mogućnosti su ograničene, pri čemu je odobrenje dobila tek nekolicina lijekova, i to pretežno za diskoidni oblik. Terapijski pristup uključuje opće mjere (zaštita od UV zračenja, prestanak pušenja, primjena vitamina D), topikalnu (kortikosteroidi, kalcineurinski inhibitori) te sistemsku terapiju (antimalarici, retinoidi, imunosupresivi i biološki lijekovi). Napredci u razumijevanju patogeneze, osobito uloge interferona i signalnih puteva urođene imunosti, potaknuli su pojačan interes i otvorili put za razvoj novih terapijskih opcija.Lupus erythematosus is a chronic autoimmune connective tissue disease that can affect nearly all organ systems, with the skin being the second most frequently involved organ. Although cutaneous manifestations may occur in isolation, without internal organ involvement, they are also present in up to 80% of patients with systemic lupus erythematosus, and in one-quarter of cases they represent the first sign of the disease. The pathogenesis of cutaneous lupus erythematosus is complex and multifactorial. It involves genetic predisposition, epigenetic changes, and environmental factors, with ultraviolet radiation being the most prominent trigger. The key role is played by the overexpression of type I interferons, which initiates a self-amplifying inflammatory loop between cells of the innate and adaptive immune system. The first widely accepted classification of cutaneous lupus erythematosus was proposed by Gilliam in 1981. It divides lesions into lupus-specific and lupus-nonspecific types. Lupus-specific lesions are characterized by the presence of interface dermatitis on histological examination and include acute, subacute, and chronic forms. To more precisely distinguish between subtypes, the Düsseldorf classification introduced in 2004 expanded Gilliam’s system by adding a fourth form, intermittent cutaneous lupus erythematosus, which includes lupus erythematosus tumidus. The diagnosis of cutaneous lupus erythematosus is based on clinical presentation, histopathological features, serological findings, and direct immunofluorescence. Despite its significant impact on quality of life, therapeutic options remain limited, with only a few approved treatments, primarily for the discoid form. The therapeutic approach includes general measures (sun protection, smoking cessation, vitamin D supplementation), topical treatment (corticosteroids, calcineurin inhibitors), and systemic therapy (antimalarials, retinoids, immunosuppressants, and biologic agents). Advances in understanding the pathogenesis, particularly the role of interferons and innate immune signaling pathways, have stimulated increased interest and opened new avenues for the development of targeted therapies
Orbital compartment syndrome
Orbitalni „compartment“ sindrom (OCS) predstavlja rijetko, ali izrazito opasno hitno
oftalmološko stanje koje nastaje uslijed naglog porasta tlaka unutar zatvorenog
anatomskog prostora orbite. Orbita je zatvoren prostor okružen sa svih strana
koštanim strukturama, osim prednje granice orbite koja se sastoji od orbitalnog
septuma i tarzalnih pločica gornjeg i donjeg kapka. Povišeni tlak unutar orbite dovodi
do smanjene perfuzije, posljedične ishemije tkiva i potencijalno ireverzibilnog
oštećenja vidne funkcije. Najčešći uzrok OCS-a je intraorbitalno krvarenje, najčešće
nakon traume, no krvarenje može nastati postoperativno ili nakon peribulbarne ili
retrobulbarne aplikacije lijekova. Rjeđe etiologije uključuju orbitalni edem, emfizem,
apscese, celulitis te sve patološke procese koji dovode do povećanja volumena
unutar orbite. Dijagnoza se temelji primarno na kliničkoj slici. Tipični simptomi
uključuju naglu i intenzivnu bol u oku, proptozu, pad vidne oštrine, ograničenje
pokreta očne jabučice, relativni aferentni pupilarni defekt te povišeni intraokularni
tlak. Iako radiološka potvrda većinom nije nužna i može odgoditi hitno liječenje,
kompjutorizirana tomografija može biti korisna u slučaju dijagnostičke nesigurnosti ili
za potvrdu etiologije. U slučajevima jasne kliničke sumnje na OCS ili intraokularnog
tlaka većeg od 40 mmHg, indicira se hitna dekompresija orbite. Standardni i najčešće
korišteni zahvat je lateralna kantotomija i kantoliza, koji je brz i tehnički jednostavan
postupak kojim se presijeca lateralni kantalni ligament kako bi se smanjio
intraorbitalni tlak. Pacijenti kod kojih se orbitalna dekompresija provede unutar dva
sata od početka simptoma imaju znatno bolju prognozu u smislu očuvanja vida.Orbital compartment syndrome (OCS) represents a rare but extremely dangerous
ophthalmologic emergency that arises due to a sudden increase in pressure within
the closed anatomical space of the orbit. The orbit is a closed space surrounded on
all sides by bony structures, except for the anterior border of the orbit which consists
of the orbital septum and the tarsal plates of the upper and lower eyelids. Elevated
pressure within the orbit leads to reduced perfusion, consequent ischemia of the
tissue, and potentially irreversible damage to visual function. The most common
cause of OCS is intraorbital hemorrhage, most often after trauma, although
hemorrhage can occur postoperatively or after peribulbar or retrobulbar
administration of medications. Less common etiologies include orbital edema,
emphysema, abscesses, cellulitis, and all pathological processes that lead to an
increase in volume within the orbit. Diagnosis is primarily based on clinical
presentation. Typical symptoms include sudden and intense eye pain, proptosis,
decreased visual acuity, restricted eye movement, relative afferent pupillary defect,
and elevated intraocular pressure. Although radiologic confirmation is mostly not
necessary and may delay urgent treatment, computed tomography may be useful in
cases of diagnostic uncertainty or to confirm the etiology. In cases of clear clinical
suspicion of OCS or intraocular pressure greater than 40 mmHg, urgent orbital
decompression is indicated. The standard and most commonly used procedure is
lateral canthotomy and cantholysis, which is a quick and technically simple procedure
in which the lateral canthal ligament is incised to reduce intraorbital pressure.
Patients in whom orbital decompression is performed within two hours from the onset
of symptoms have a significantly better prognosis in terms of vision preservation
Perioperative volume replacement in a patient with chronic kidney disease
Kronična bubrežna bolest (KBB) je često neprepoznat klinički sindrom obilježen progresivnim i ireverzibilnim gubitkom bubrežne strukture i funkcije. Bubreg ima ključnu ulogu u održavanju homeostaze volumena, elektrolita i acidobazne ravnoteže. Obzirom da u bolesnika s KBB-om dolazi do poremećaja u regulaciji homeostaze i pacijenti imaju brojne komorbiditete, volumna nadoknada je posebno izazovna. Neadekvatan monitoring volumnog statusa te neadekvatni odabir vrste i količine tekućine može dovesti do volumnog preopterećenja, metaboličke acidoze, disbalansa elektrolita, akutne ozljede bubrega (AOB) i progresije osnovne bolesti. Idealna tekućina za volumnu nadoknadu ne postoji. Predmet stalne rasprave je izbor između kristaloidnih i koloidnih otopina. Kristaloidi su najčešće korištene tekućine, posebice 0,9%-tna otopina natrijevog klorida. Iako je njezin drugi naziv fiziološka otopina, brojna istraživanja povezuju njezinu opsežnu primjenu s razvojem hiperkloremične metaboličke acidoze, bubrežnom hipoperfuzijom i retencijom tekućine. S druge strane, balansirane kristaloidne otopine su svojim sastavom sličnije osmolarnosti plazme te su istraživanja uočila manju incidenciju perioperacijskih komplikacija nakon njihove primjene. Koloidi su djelotvorniji u ekspanziji intravaskularnog volumena, no povezani su s mnogim nuspojavama poput oštećenja bubrežne funkcije, koagulopatijama i reakcijama preosjetljivosti. Zbog toga primjena koloida u bolesnika s KBB-om treba biti ograničena na strogo indicirane situacije poput akutnih krvarenja. Ključ uspješne regulacije volumnog statusa ovih pacijenata je individualizirani pristup. Trenutno nema standardiziranih smjernica pa se strategije perioperacijske volumne nadoknade u bolesnika s KBB-om temelje na kliničkom iskustvu i istraživanjima. Međutim, većina istraživanja je provedena na pacijentima s normalnom bubrežnom funkcijom ili na kritično bolesnima u jedinici intenzivnog liječenja (JIL). Stoga je nužno provesti dodatna istraživanja kako bi se razvile jasno definirane smjernice za ovu skupinu pacijenata.Chronic kidney disease (CKD) is a frequently unrecognized clinical syndrome characterized by progressive and irreversible loss of renal structure and function. The kidneys play a key role in maintaining volume homeostasis, electrolyte balance, and acid-base equilibrium. In patients with CKD, disturbances in these regulatory mechanisms, combined with the presence of numerous comorbidities, make fluid replacement particularly challenging. Inadequate monitoring of fluid status and improper selection of the type and volume of fluid can lead to volume overload, metabolic acidosis, electrolyte imbalance, acute kidney injury, and progression of the underlying disease. There is no ideal fluid for volume replacement, and the choice between crystalloid and colloid solutions remains a topic of ongoing debate. Crystalloids are the most commonly used fluids, particularly 0.9% sodium chloride. Although often referred to as "normal saline," extensive use of this solution has been associated with hyperchloremic metabolic acidosis, renal hypoperfusion, and fluid retention. In contrast, balanced crystalloids, with a composition more closely resembling plasma osmolarity, have been associated with a lower incidence of perioperative complications. Colloids are more effective in expanding intravascular volume but are linked to numerous adverse effects, including impaired renal function, coagulopathies, and hypersensitivity reactions. Consequently, the use of colloids in CKD patients should be limited to strictly indicated situations, such as acute hemorrhage. The key to successful management of fluid status in these patients lies in an individualized approach. Currently, there are no standardized guidelines, and perioperative fluid replacement strategies for CKD patients rely on clinical experience and available research. However, most studies have been conducted on patients with normal renal function or critically ill patients in intensive care units. Therefore, further research is essential to develop well-defined guidelines for this patient population