Veterinary medicine - Repository of PHD, master's thesis

Veterinary medicine - Repository of PHD, master's thesis
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    Protection and safety of nurses/technicians in the Republic of Croatia during a stabbing incident

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    Ubodnim incidentom smatra se ozljeda kože uzrokovana iglom ili oštrim predmetom. Prema procjeni Svjetske zdravstvene organizacije godišnje mu je u svijetu profesionalno izloženo preko dva milijuna zdravstvenih radnika. Prema procjeni Američkog centra za kontrolu i prevenciju bolesti primjenom standardnih mjera zaštite moguće je prevenirati 86 % ubodnih incidenata. Kako bi se smanjio rizik od infekcije nastale prilikom ubodnog incidenta, u svakodnevnom radu treba se držati općih mjera zaštite te nakon incidentne situacije provoditi specifične mjere. U našoj zemlji prema Pravilniku o načinu provođenja mjera zaštite radi sprečavanja i nastanka ozljede oštrim predmetima, svaka medicinska sestra/tehničar mora biti upoznata s mogućnošću nastanka ubodnog incidenta za vrijeme rukovanja oštrim predmetima u radu. Nastane li ubodni incident, poslodavac je obavezan odmah poduzeti mjere u skladu s posebnim propisima o uvjetima i načinu provođenja preventivnih i kontrolnih mjera za sprečavanje bolničkih infekcija te osigurati pružanje zdravstvene skrbi ozlijeđenim radnicima. Koraci koje je potrebno poduzeti kod postekspozicijske profilakse sastoje se od: postupka s mjestom ekspozicije (ispiranje kontaminiranog dijela vodom i sapunom), prijave profesionalne ekspozicije, evaluacije ekspozicije, evaluacije izvornog bolesnika te postekspozicijski postupci koji se hitno započinju u slučaju zaraze HIV-om ili HBV-om. Iako su djelatnici dužni prijaviti svaki ubodni incident bolničkom povjerenstvu ustanove u kojoj rade, procjenjuje se da godišnje u Hrvatskoj ostane neprijavljeno 32.000 incidenata. Broj prijavljenih slučajeva godišnje ne pokazuje trend smanjenja, stoga je potrebno dosljedno primjenjivati dostupne mjere zaštite koje su trenutno dostupne te kontinuirano podizati svijest među zdravstvenim djelatnicima o riziku u radu s oštrim predmetima.A needlestick incident is defined as an injury of the skin caused by a needle or sharp object. According to the World Health Organization's estimates, over two million healthcare workers worldwide are professionally exposed to needlestick incidents annually. The Centres for Disease Control and Prevention suggest that implementing standard protective measures could prevent 86% of needlestick incidents. To reduce the risk of infection adherence to general protective measures in daily work and the implementation of specific measures following an incident are crucial. In our country, in accordance with the Regulation on the Implementation of Measures for the Prevention of Injuries Caused by Sharp Objects (Official Gazette 39/2020), every nurse must be familiar with the possibility of needlestick incidents while handling sharp objects at work. In the case of a needlestick incident, employers are obligated to promptly take actions in accordance with specific regulations on the conditions and methods of implementing preventive and control measures to combat hospital infections, ensuring healthcare provision for injured workers. Post-exposure prophylaxis involves several steps: the procedure at the exposure site (rinsing the contaminated area with water and soap), reporting professional exposure, evaluating the exposure, evaluating the source patient, and implementing post-exposure procedures that urgently commence in case of HIV or HBV infection. Despite the obligation for employees to report each needlestick incident to the hospital commission of the institution, an estimated 32,000 incidents in Croatia go unreported annually. The yearly reported cases do not exhibit a decreasing trend, emphasizing the need for consistent provision of available protective measures and continuous awareness-raising among healthcare professionals regarding the risks associated with working with sharp objects

    A case report of cStage IIIB squamous cell lung carcinoma completely resected after downstaging with neoadjuvant therapy

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    Background: The most effective method and length of time for administering adjuvant immunotherapy after surgery for non-small cell lung cancer (NSCLC) are still unknown. Various clinical trials have utilized diverse strategies for adjuvant treatment. In this case, we explore the potential benefits of neoadjuvant immunotherapy combined with chemotherapy in managing locally advanced lung squamous carcinoma, which often poses challenges for treatment. This multimodal approach aims to downstage tumors and optimize surgical outcomes. Case description: Following a diagnosis of stage IIIB lung cancer, the patient underwent three cycles of neoadjuvant therapy using sintilimab, Abraxane, and Lobaplatin, resulting in a significant 45% reduction in tumor size. Subsequently, a right lower lobe lobectomy and systematic lymphadenectomy were performed using a uniportal video-assisted thoracic surgery (VATS) approach. Postoperative analysis revealed negative lymph nodes, with only a 5-mm residual tumor in the tumor bed, downstaging the cancer to IA1. Remarkably, the patient experienced a smooth recovery without any postoperative complications. One cycle of adjuvant therapy was administered following the operation to further support the patient's recovery and minimize the risk of disease recurrence. This comprehensive treatment approach underscores the importance of neoadjuvant therapy in optimizing surgical outcomes and improving long-term prognosis for patients with locally advanced lung cancer. Conclusions: For patients with stage III locally advanced lung squamous carcinoma, the combination of Sintilimab and Platinum-based drugs can be used as a neoadjuvant therapy which can reduce the difficulty of the operation

    Equivalent: Acinetobacter Baumannii Pneumonia Associated with Mechanical Ventilation in COVID-19 Pandemic

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    Infekcije uzrokovane bakterijom Acinetobacter baumannii predstavljaju veliki javnozdravstveni problem. Acinetobacter baumannii kontaminira bolničko okruženje, kožu i sluznice pacijenata te se prenosi rukama osoblja uzrokujući oportunističke infekcije kao što su upale pluća povezane s mehaničkom ventilacijom, bakterijemije, infekcije rana te urinarne infekcije. Ventilatorom uzrokovana upala pluća druga je po učestalosti nozokomijalna infekcija u jedinicama intenzivnog liječenja. Vodeći čimbenik rizika za razvoj ventilatorom uzrokovane upale pluća jest invazivna mehanička ventilacija. U pacijenata s bolešću COVID-19, liječenje u jedinicama intenzivnog liječenja često je zahtijevalo intubaciju i uporabu mehaničke ventilacije izlažući ih riziku od razvoja ventilatorom uzrokovane upale pluća. S obzirom na brojna preklapanja u kliničkoj slici COVID upale pluća i upale pluća povezane s ventilatorom, teško je sa sigurnošću odrediti njezinu prevalenciju. Oštećenja pluća uzrokovana bolešću COVID-19, imunosupresivna terapija, često profilaktičko korištenje antibiotika i organizacijske teškoće – prenapučenost u jedinicama intenzivnog liječenja, manjak osoblja, potreba za zaštitom osoblja od virusa SARS-CoV-2 (engl. Severe acute respiratory syndrome coronavirus 2) infekcije i dr., pridonijeli su povećanoj pojavnosti ventilatorom izazvane upale pluća uzrokovane Acinetobacter baumannii u pacijenata oboljelih od COVID-a. Brojni mehanizmi otpornosti na antibiotike, uz posljedično sve veću prevalenciju višestruko otpornih sojeva Acinetobacter baumannii predstavljaju izazov u liječenju. U osjetljivih sojeva, monoterapija karbapenemima dovodi do pozitivnog ishoda. Liječenje karbapenem-otpornih Acinetobacter baumannii sojeva u kompliciranim infekcijama provodi se uglavnom kolistinom. Kolistin se može primjenjivati intravenski i inhalacijski te ga se preporučuje koristiti u kombinaciji s drugim djelotvornim antibioticima.Infections caused by Acinetobacter baumannii are a major public health issue. Acinetobacter baumannii contaminates the hospital environment, skin, and mucous membranes of patients and is transmitted by the hands of staff, causing opportunistic infections such as pneumonia associated with mechanical ventilation, bacteremia, wound infections, and urinary tract infections. Ventilator-associated pneumonia is the second most common nosocomial infection in the intensive care units. The leading risk factor for the development of ventilator-associated pneumonia is invasive mechanical ventilation. In the patients with COVID-19 disease, the treatment in intensive care units often required intubation and the use of mechanical ventilation, exposing them to the risk of developing ventilator-associated pneumonia. Given the numerous overlaps in the clinical picture of COVID-19 pneumonia and ventilator-associated pneumonia, it is difficult to determine its prevalence with certainty. Lung damage caused by COVID-19, immunosuppressive therapy, frequent prophylactic use of antibiotics, and organizational difficulties (overcrowding in intensive care units, staff shortages, the need to protect staff from severe acute respiratory syndrome coronavirus 2 infection, etc.) have contributed to the increased incidence of ventilatorassociated pneumonia in COVID-19 patients. Numerous mechanisms of antibiotic resistance and the increasing prevalence of multidrug-resistant strains such as carbapenemresistant Acinetobacter baumannii present a challenge in treatment. In susceptible strains, monotherapy with carbapenems leads to a positive outcome. The treatment of carbapenem-resistant Acinetobacter baumannii strains in complicated infections is carried out mainly with colistin. Colistin can be administered intravenously or by inhalation, and it’s use in combination with other effective antibiotics is recommended

    Bacteriuria in Paediatric Oncology Patients: Clinical Features, Distribution and Antimicrobial Susceptibility of Bacterial Pathogens at University Hospital Centre Zagreb, Croatia over a 4-Year Period

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    Bacteriuria in paediatric oncology patients have not been well studied. This retrospective study analysed clinical features, distribution and antimicrobial susceptibility of bacterial pathogens cultured from urine in paediatric oncology patients over a 4-year period (2019–2022). A total of 143 episodes of bacteriuria were documented in 74 patients. Neutropenia was present in 17.5% (25/143), symptoms in 25.9% (37/143) and urinary catheter in 7.0% (10/143) episodes. Symptomatic bacteriuria episodes were statistically significantly more frequent in patients with neutropenia (p = 0.0232). The most common bacterial pathogens were Escherichia coli (n = 49; 32.2%), Klebsiella spp. (n = 34; 22.4%), Pseudomonas aeruginosa (n = 22; 14.5%) and Enterococcus spp. (n = 21; 13.8%). Extended-spectrum β-lactamases-producing (ESBL) Enterobacterales were found in 11 episodes (11/143; 7.7%) with the highest proportion among Klebsiella pneumoniae isolates (n = 7/34; 20.6%). No carbapenem-resistant Enterobacterales, multidrug-resistant P. aeruginosa or vancomycin-resistant Enterococcus spp. were found. The most important novelties are demonstrating P. aeruginosa as one of the prominent bacteriuria pathogens in this patient population, presence of ESBL isolates and carbapenem-resistant P. aeruginosa later during hospitalization highlights the need for appropriate antimicrobial treatment. However, because of the small number of symptomatic patients, further studies are needed to clarify the importance of including urine culture in the diagnostic process in patients with febrile neutropenia

    A Comparative Analysis of the SARC-F Questionnaire and the Malnutrition–Inflammation Score for Sarcopenia Risk Assessment and Negative Outcome Probability in Chronic Hemodialysis Patients

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    Background/Objectives: Protein–energy wasting (PEW) and sarcopenia are common in chronic hemodialysis (HD) patients, leading to numerous complications and increased mortality. This study aimed to compare the reliability of the SARC-F (Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls) and the Malnutrition–Inflammation Score (MIS) in assessing sarcopenia and predicting negative outcomes in HD patients. Methods: This cross-sectional study enrolled 109 HD patients. Nutritional assessments were performed, and blood samples were taken for routine blood laboratory investigations. The MIS was used as a scoring system to represent the severity of PEW, while the SARC-F was applied as an indicator of sarcopenia risk and general functional capacity. A multivariable logistic regression was conducted to analyze the association of several predictors with a negative cross-sectional outcome (death). Results: Patients with SARC-F scores ≥ 4 and MISs ≥ 6 were older, had significantly lower albumin and prealbumin levels, and more severe anemia. They were also more likely to report weight loss and poor appetite. A higher MIS was closely associated with unfavourable nutritional status according to the International Society of Renal Nutrition and Metabolism (ISRNM) criteria for PEW. However, in 71.25% of patients with satisfactory functional capacity (SARC-F scores 0–3), some form of PEW was still observed. After performing logistic regression modelling, only the MIS remained strongly associated with the probability of a negative outcome. Conclusions: The SARC-F alone often did not correspond to an increased sarcopenia risk or clear clinical and biochemical indicators of PEW in HD patients. When assessing nutritional risk in this group, it is recommended to use more detailed tools, such as the MIS, to ensure the accurate identification of those at the highest risk for negative outcomes

    Proteomic exploration of potential blood biomarkers in haemophilic arthropathy

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    Background and aims: The pathophysiology of haemophilic arthropathy (HA) is complex and largely undefined. Proteomic analyses provide insights into the intricate mechanisms of the HA.Our study aimed to identify differentially expressed proteins in relation to the severity of HA, explore their pathophysiological roles, and evaluate their potential as HA biomarkers. Methods: Our cross-sectional observational study encompassed 30 HA patients and 15 healthy subjects. Plasma samples were pooled into three groups of 15 samples from those with severe haemophilic arthropathy (sHA), mild haemophilic arthropathy (mHA) and healthy controls. Proteomic analysis was performed using liquid chromatography-mass spectrometry. The severity of HA was assessed using the World Federation of Haemophilia Physical Examination Score and ultrasonography following the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) guidelines. Results: A total of 788 proteins were identified, with 97% of the uniquely identified proteins being expressed in all analysed groups. We identified several up and downregulated proteins across the groups that were mainly related to inflammatory and immunity-modulating processes, as well as joint degeneration. We highlighted ten proteins relevant for the development of HA: cathepsin G, endoplasmic reticulum aminopeptidase 2, S100-A9, insulin-like growth factor I, apolipoprotein (a), osteopontin, pregnancy zone protein, cartilage oligomeric matrix protein, CD44, and cadherin-related family member 2. Conclusion: Our analysis identified several proteins that shed further light on the distinctive pathogenesis of HA and could serve for biomarker research. However, these results need to be validated on a larger patient group

    Sex-Related Differences in the Associations between Adiponectin and Serum Lipoproteins in Healthy Subjects and Patients with Metabolic Syndrome

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    The strong associations between the serum levels of adiponectin and the lipoprotein subclasses observed in healthy subjects are much weaker in patients with metabolic syndrome (MS). However, the impact of sex on these associations remained unexplored. Therefore, in the present study, we examined associations between adiponectin and the lipoprotein subclasses, analyzed by nuclear magnetic resonance spectroscopy, separately in healthy females and males, as well as in females and males with MS. We observed negative correlations between adiponectin and VLDL, IDL, and small-dense LDL in healthy males, but neither in healthy females nor in females or males with MS. Additionally, adiponectin was positively correlated with some HDL subclasses in healthy males and females with MS, but not in healthy females or males with MS. Adjusting for age and either body mass index, waist circumference, C-reactive protein, or interleukin-6 weakened the associations between adiponectin and VLDL and IDL but not small-dense LDL. The adjustment weakened the associations between adiponectin and HDL in healthy males but not in females with MS. Based on our results, we conclude that sex and the presence of MS are strong determinants of the associations between adiponectin and serum lipoproteins and that the complex regulatory network comprising adiponectin and other molecular players involved in the regulation of lipoprotein metabolism is primarily operative in healthy males and females with MS

    Bone marrow stromal cells enhance differentiation of acute myeloid leukemia induced by pyrimidine synthesis inhibitors

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    Acute myeloid leukemia (AML) is a heterogeneous group of hematological malignancies characterized by differentiation arrest, high relapse rates, and poor survival. The bone marrow (BM) microenvironment is recognized as a critical mediator of drug resistance and a primary site responsible for AML relapse. Our previous study reported that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) induces AML cell differentiation by inhibiting pyrimidine synthesis and activating Checkpoint kinase 1. Although the protective effect of BM stroma on leukemia cells in response to cytotoxic drugs is well-documented, its effect on AML differentiation remains less explored. In this study, we investigated the impact of stromal cell lines and primary mesenchymal stromal cells (MSCs) on AML cell line differentiation triggered by AICAr and brequinar, a known dihydroorotate dehydrogenase (DHODH) inhibitor. Our findings indicate that the mouse MS-5 stromal cell line, known for its cytoprotective effects, does not inhibit AML cell differentiation induced by pyrimidine synthesis inhibitors. Interestingly, AICAr caused morphological changes and growth arrest in MS-5 stromal cells via an AMP-activated protein kinase (AMPK)-dependent pathway. Human stromal cell lines HS-5 and HS-27, as well as primary MSCs isolated from patient bone marrow, were superior in promoting AML differentiation compared with mouse cells in response to AICAr and brequinar, with the inhibitors not significantly affecting the stromal cells themselves. In conclusion, our study highlights the supportive role of human BM MSCs in enhancing the differentiation effects of pyrimidine synthesis inhibitors on AML cells, suggesting that AML treatment strategies focusing on differentiation rather than cell killing may be successful in clinical settings. NEW & NOTEWORTHY This study is the first to demonstrate that human stromal cell lines and primary mesenchymal stromal cells from patients enhance the in vitro differentiation of acute myeloid leukemia (AML) cells induced by pyrimidine synthesis inhibitors, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr), and brequinar. Furthermore, this is the first report to show that AICAr affects mouse bone marrow stromal cells by activating AMP-activated protein kinase (AMPK) and that human stromal cells are superior to mouse cells for testing the effects of drugs on AML differentiation

    C4d Is an Independent Predictor of the Kidney Failure in Primary IgA Nephropathy

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    Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study was to investigate the prevalence and prognostic significance of C4d in our cohort of patients with primary IgA nephropathy (pIgAN). Methods: Patients with pIgAN were recruited from a hospital register of kidney biopsies of the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb. Additional immunohistochemistry staining for C4d was performed on paraffin-embedded kidney tissue, and patients were stratified into being C4d positive or C4d negative. The clinical and histologic features of patients were analyzed and compared regarding C4d positivity. The primary outcome was defined as kidney failure (KF), and predictor variables of KF and renal survival were analyzed. Results: Of a total of 95 patients with pIgAN included in the study, C4d was present in 43 (45.3%). C4d-positive patients had a higher value of systolic (p = 0.039) and diastolic (p = 0.006) blood pressure at diagnosis as well as higher 24 h proteinuria (p = 0.018), serum urate (p = 0.033), and lower eGFR (p < 0.001). C4d-positive patients had worse renal survival (p < 0.001), higher rates of disease progression to KF (p < 0.001), and higher proteinuria (p < 0.001) and lower eGFR (p < 0.001) at the last follow-up. Glomerular C4d was an independent predictor of disease progression to KF (HR = 5.87 [0.95 CI 1.06–32.44], p = 0.032). Conclusions: C4d is an independent predictor of disease progression in patients with pIgAN. C4d may be used as an additional marker of progressive disease course in IgAN. The therapeutic implications of C4d status in IgAN, particularly in terms of complement inhibitors application, are not yet known

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    Veterinary medicine - Repository of PHD, master's thesis is based in Croatia
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