Klinički Bolnički Centar Rijeka

Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians.

Cytomegaloviruses (CMVs) represent prototypic viruses of the beta-subgroup of herpesviruses. Murine cytomegalovirus (MCMV) infects mice as its natural host. Among viruses, CMVs have evolved the most extensive genetic repertoire to subvert MHC class I functions. To date three MCMV proteins have been identified which affect MHC I complexes. They are encoded by members of large virus-specific gene families located at either flanking region of the 235 kb MCMV genome. The MHC I subversive genes belong to the early class of genes and code for type I transmembrane glycoproteins. The m152-encoded 37/40 kDa glycoprotein interacts with MHC I transiently and retains class I complexes in the endoplasmic reticulum (ER) Golgi intermediate compartment on its journey to the endolysosome. In contrast, the m06-encoded glycoprotein of 48 kDa complexes tightly with ternary MHC class I molecules in the FR. Due to sorting signals in its cytoplasmic tail, gp48 redirects MHC I to endolysosomal compartments for proteolytic destruction. Likewise, the 34 kDa glycoprotein encoded by m04 binds tightly to MHC class I complexes in the ER but the gp34/MHC I complex reaches the plasma membrane. The CD8+ T-cell-dependent attenuation of a m152 deletion mutant virus proves for the first time that inhibition of antigen presentation is indeed essential for the biological fitness of CMVs in vivo.

Lung cancer is one of the most common malignant diseases and is amongst the leading causes of death. Cell-mediated immune response and cytokines could play an important role in antitumour immunity. The aim of the study was to evaluate the cytokines', tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6, releasing capacity in patients with lung carcinoma and benign lung disease. A group of 41 patients were tested for the production of TNF-alpha, IL-1beta and IL-6 in bronchoalveolar lavage (BAL) and blood. The levels of cytokines in the lung cancer patients were: (1) in BAL - IL-6, 173 +/- 85 pg/ml; TNF-alpha, 170 +/- 116 pg/ml; and IL-1beta, 473 +/- 440 pg/ml; (2) in the blood - IL-6, 197 +/- 53 pg/ml; TNF-alpha, 311 +/- 202 pg/ml; and IL-1beta, 915 +/- 239 pg/ml. Alveolar macrophages of the patients with a lung cancer secreted significantly more cytokines, IL-6 (P = 0.0004) and IL-1beta (P = 0.0047), than alveolar macrophages of the patients with a nonmalignant lung cancer. However, significantly lower levels of cytokine production by the BAL cells were found in patients with small cell lung cancer. This production decreased further in phase IV of nonsmall cell lung cancer.

Akutna limfoblastična leukemija najčešća je maligna bolest u djece. Primjena terapije prilagođene skupinama rizika rezultirala je izlječenjem u otprilike 80 % bolesnika, čime spada u jednu od najuspješnijih priča u povijesti onkologije. Poboljšanom sustavnom i intratekalnom terapijom danas je u većine djece moguće izostaviti profilaktičko zračenje središnjeg živčanog sustava. Kontinuirani napredak farmakogenomike dat će u bliskoj budućnosti nov uvid u pedijatrijsku leukemogenezu i izbor optimalne terapije. Kroz to vrijeme potrebno je imati na umu kasne učinke terapije u značajnog dijela preživjelih, te intenzivirati preventivne mjere i njihovo rano otkrivanje.

INTRODUCTION: Cobas 6000 (Roche, Germany) is biochemistry analyzer for spectrophotometric, immunoturbidimetric and ion-selective determination of biochemical analytes. Hereby we present analytical validation with emphasis on method performance judgment for routine operation. MATERIALS AND METHODS: Validation was made for 30 analytes (metabolites, enzymes, trace elements, specific proteins and electrolytes). Research included determination of within-run (N = 20) and between-run imprecision (N = 30), inaccuracy (N = 30) and method comparison with routine analyzer (Beckman Coulter AU640) (N = 50). For validation of complete analytical process we calculated total error (TE). Results were judged according to quality specification criteria given by European Working Group. RESULTS: Within-run imprecision CVs were all below 5% except for cholesterol, triglycerides, IgA and IgM. Between-run CVs for all analytes were below 10%. Analytes that did not meet the required specifications for imprecision were: total protein, albumin, calcium, sodium, chloride, immunoglobulins and HDL cholesterol. Analytes that did not fulfill requirements for inaccuracy were: total protein, calcium, sodium and chloride. Analytes that deviated from quality specifications for total error were: total protein, albumin, calcium, sodium, chloride and IgM. Passing-Bablok regression analysis provided linear equation and 95% confidence interval for intercept and slope. Complete accordance with routine analyzer Beckman Coulter AU640 showed small number of analytes. Other analytes showed small proportional and/or small constant difference and therefore need to be adjusted for routine operation. CONCLUSIONS: Regarding low CV values, tested analyzer has satisfactory accuracy and precision and is extremely stable. Except for analytes that are coherent on both analyzers, some analytes require adjustments of slope and intercept for complete accordance.

AIM: To examine the role of perceived stressfulness of trauma exposure and economic, social, occupational, educational, and familial adaptation after trauma in posttraumatic stress disorder (PTSD) and depression in displaced war survivors. METHODS: A cross-sectional survey was conducted between March 2000 and July 2002 with a sample of 173 internally displaced persons or refugees and 167 matched controls in Croatia. Clinical measures included Structured Clinical Interview for DSM-IV and Clinician-Administered PTSD Scale. RESULTS: Displaced war survivors reported the exposure to a mean±standard deviation of 13.1±8.3 war stressors, including combat, torture, serious injury, death of close persons, and loss of property. Compared to controls, they reported higher rates of marked to severe impact of war on family (16.2% vs 51.6%), social (7.2% vs 43.5%), economic (12.6% vs 55.4%), occupational (1.8% vs 15.9%), and educational (2.4% vs 8.8%) adaptation. In two logistic regression analyses, the strongest predictor of PTSD and depression was high level of perceived distress during trauma exposure. PTSD but not depression was associated with economic, social, occupational, educational, and familial adaptation after trauma. CONCLUSION: Displaced survivors who experienced multiple war events perceived greater negative impact of war on their life domains compared to individuals who lived in a war setting but had no trauma exposure. The most important determinant of psychological outcomes was perceived stressfulness of war stressors. Although post-trauma adaptation in different life spheres had an impact, its effect was not robust and consistent across disorders. These findings suggest that it would be effective to use a trauma-focused approach in rehabilitation of war survivors.

BACKGROUND: Paediatric cardiac services are poorly developed or totally absent in underdeveloped countries. Institutions, foundations and interested individuals in those nations in which sophisticated paediatric cardiac surgery is practised have the ability to alleviate this problem by sponsoring paediatric cardio-surgical missions to provide care, and train local caregivers in developing, transitional, and third world countries. The ultimate benefit of such a programme is to improve the surgical abilities of the host institution. The purpose of this report is to present the impact of our programme over a period of 14 years. METHODS: We specifically reviewed our database of patients from our missions, our team lists, surgical results, and the number and type of personnel trained in the institutions that we have assisted. In order for the institution to be entered into the study, the foundation had to provide at least 2 months of training. In addition, the institution had to respond to a simple questionnaire concerning the number and types of surgery performed at their facility before and after intervention by the foundation. RESULTS: We made 140 trips to 27 institutions in 19 countries, with 12 of the visited institutions qualifying for inclusion. Of these, 9 institutions reported an increase in the number and complexity of cases currently being performed in their facility since the team intervened. This goal had not been accomplished in 3 institutions. The reasons for failure included the economic situation of the country, hospital and national politics, personality conflicts, and continued lack of hardware and disposables. CONCLUSIONS: Paediatric cardiac service assistance can improve local services. A significant commitment is required by all parties involved.

An updated and evidence-based checklist of Mediterranean Sea fishes is provided. Each of the fish species in the Mediterranean Sea listed here was either listed in the last published checklist of the Mediterranean fishes or in other articles, reports or new records, and the checklist is critically assessed. Out of the assessed 791 species previously reported from the Mediterranean, the presence of 759 species is confirmed while 32 species are excluded from the new checklist, by lacking evidence of presence or representing obvious taxonomic confusions. The net increase in known Mediterranean fish species richness since the last checklist is 11%. The non-native Mediterranean species now represent 22.1% (168 species) of the known Mediterranean fish diversity. The evidence-based protocol applied here provides a reliable checklist of marine fishes, for which each of the included species has indeed been recorded at least once within the discussed geographic area in the Mediterranean Sea.

Low back pain is defined as pain and discomfort, localised below the costal margin and above the inferior gluteal folds, with or without leg pain. It is one of the most commonest cause of seeking physician office visits, secound cause of sick leave, and because of high direct and indirect costs it has great medical, social and economic impact for individual, family and society. Non-specific low back pain is defined as low back pain not attributed to recognisable, known specific pathology and specific low back pain which has known pathomorfological cause. For most patients with low back pain a thorough history taking and clinical examination are suffitient. Extended diagnostic analysis are needed in the case of nerve root pain/radicular pain and serious spinal pathology, respectively after identification of red flags. Moreover, great attention has to be achieved at psychosocial factors or so called yellow flags which increase the risk of developing chronic low back pain and long term disability (including work loss associated with low back pain).

COVID-19 vaccines prevent severe forms of the disease, but do not warrant complete protection against breakthrough infections. This could be due to suboptimal mucosal immunity at the site of virus entry, given that all currently approved vaccines are administered via the intramuscular route. In this study, we assessed humoral and cellular immune responses in BALB/c mice after intranasal and intramuscular immunization with adenoviral vector ChAdOx1-S expressing full-length Spike protein of SARS-CoV-2. We showed that both routes of vaccination induced a potent IgG antibody response, as well as robust neutralizing capacity, but intranasal vaccination elicited a superior IgA antibody titer in the sera and in the respiratory mucosa. Bronchoalveolar lavage from intranasally immunized mice efficiently neutralized SARS-CoV-2, which has not been the case in intramuscularly immunized group. Moreover, substantially higher percentages of epitope-specific CD8 T cells exhibiting a tissue resident phenotype were found in the lungs of intranasally immunized animals. Finally, both intranasal and intramuscular vaccination with ChAdOx1-S efficiently protected the mice after the challenge with recombinant herpesvirus expressing the Spike protein. Our results demonstrate that intranasal application of adenoviral vector ChAdOx1-S induces superior mucosal immunity and therefore could be a promising strategy for putting the COVID-19 pandemic under control.

Journal Article Hormonal treatment of impetigo herpetiformis Get access M. GLIGORA, M. GLIGORA Department of Dermatology, Klinicka bolnica "Dr Z.Kucic", 51000 Rijeka, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar Z. KOLAVIO Z. KOLAVIO Department of Dermatology, Klinicka bolnica "Dr Z.Kucic", 51000 Rijeka, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue 2, 1 August 1982, Page 253, https://doi.org/10.1111/j.1365-2133.1982.tb00353.x Published: 01 August 1982

This review focuses first on conceptual chaos and different connotations in psychosomatic medicine, then on new perspectives on comorbidity and multimorbidity, especially from epigenetics perspective. Comorbidity is one of the greatest research and clinical challenges to contemporary psychiatry and psychosomatic medicine. Recently altered gene expression due to epigenetic regulation has been implicated in the development of multifarious mental disorders and somatic diseases. The potential relevance of epigenetics for better understanding and more successful treatment of comorbidity and multimorbidity is described.

Pancreatic β-cell death or dysfunction mediated by oxidative stress underlies the development and progression of diabetes mellitus. In the present study, we tested extracts from the edible mushroom Lactarius deterrimus and the chestnut Castanea sativa , as well as their mixture (MIX Ld / Cs ), for potential beneficial effects on streptozotocin (STZ)-induced pancreatic β-cell death. Analysis of chelating effects, reducing power and radical-scavenging assays revealed strong antioxidant effects of the C. sativa extract and MIX Ld / Cs , while the L. deterrimus extract displayed a weak to moderate effect. The antioxidative effect of the chestnut extract corresponds with the high content of phenolics and flavonoids identified by HPLC analysis. In contrast, the mushroom extract contains relatively small amounts of phenols and flavonoids. However, both extracts, and especially their combination MIX Ld / Cs , increased cell viability after the STZ treatment as a result of a significant reduction of DNA damage and improved redox status. The chestnut extract and MIX Ld / Cs significantly lowered the STZ-induced increases in superoxide dismutase and catalase activities, while the mushroom extract had no impact on the activities of these antioxidant enzymes. However, the L. deterrimus extract exhibited good NO-scavenging activity. Different mechanisms that underlie antioxidant effects of the mushroom and chestnut extracts were discussed. When combined as in the MIX Ld / Cs , the extracts exhibited diverse but synergistic actions that ultimately exerted beneficial and protective effects against STZ-induced pancreatic β-cell death.

The aim of this report is to present a case of a patient with a recurrent nasal cavity amelanotic melanoma (AM), with emphasis on diagnosis and therapy options of this clinical entity. A 65-year-old female patient presented with pain in the right cheek region and nasal obstruction. In 2013, she was diagnosed with mucosal melanoma (MM) of the left nasal cavity. After endoscopic surgery and radiotherapy, the patient was followed by the oncology team. Five years after the initial diagnosis, rhinoscopy showed a tumorous formation in the right nasal cavity. The tumor mass was without black discoloration and was the same color as the surrounding nasal mucosa. Microscopic examination after biopsy of the tumor confirmed amelanotic MM. The patient underwent an additional endoscopic surgery. A complete standard diagnostic workup for MM found metastases in head and neck lymph nodes, on both sides. MMs of head and neck are uncommon malignancies. Unique biology of MM cells causes a high rate of recurrences. This report presents an example of recurrent AM of the nasal cavity, in treatment with checkpoint inhibitor (pembrolizumab), which could provide a good therapy option for patients with MM.

Umbilical cord blood (UCB) is a source of the rare but precious primitive hematopoietic stem cells (HSC) and progenitor cells that can reconstitute the hematopoietic system in patients with malignant and nonmalignant disorders treated with myeloablative therapy. UCB cells possess an enhanced capacity for progenitor cell proliferation and self-renewal in vitro. UCB is usually discarded, and it exists in almost limitless supply. The blood remaining in the delivered placenta is safely and easily collected and stored. The predominant collection procedure currently practiced involves a relatively simple venipuncture, followed by gravity drainage into a standard sterile anti-coagulant-filled blood bag, using a closed system, similar to the one utilized on whole blood collection. After aliquots have been removed for routine testing, the units are cryopreserved and stored in liquid nitrogen. UCB banks are being established throughout the world and UCB units are collected for allogeneic unrelated and related HSC transplantation. In unrelated cord blood banks donated UCB units are collected and stored for allogeneic use in patients who do not have an identified HLA matched relative. UCB banks report available units to national and international donor registries. The second model of UCB banking is referred to as family banking, where UCB is stored for the benefit of the donor or their family members. After more than one decade of clinical experience, it is currently accepted that UCB transplants, related and unrelated, are equivalent to or might compare favorably with bone marrow (BM) transplants, especially in children. Initial studies of long-term survival in children with both malignant and non-malignant hematologic disorders, who were transplanted with UCB from a sibling donor, demonstrated comparable or superior survival to children who received BM transplantation. One factor that limits the use of UCB transplantation in adult patients is the relatively limited number of HSC that may be harvested from umbilical cord, resulting in a slower time to engraftment and higher transplant related mortality, mainly due to the long aplasia period after transplantation and susceptibility to viral and fungal infections. Despite prolonged periods of aplasia, the apparent reduction in the incidence and severity of graft versus host disease (GVHD) may in turn underline comparable rates of survival in some series comparing UCB to adult-donor sources. The "naive" nature of UCB lymphocytes may explain the lower incidence and severity of GVHD encountered in UCB transplantation compared to the allogeneic BM transplant setting. UCB transplantation does not seem to be associated with increased rates of disease relapse. The available data suggest that nucleated cell dose in UK unit should be the primary criterion for donor selection. In 1991, the UCB transplantation program was established at the Zagreb University Hospital Center for related transplants, and until now 4 UCB transplantations have been performed successfully. In order to speed up the engraftment rate, several strategies such as multiple UCB transplants and ex vivo expansion of HSC have been assayed. The current strategies are focused on the development of much more efficient technologies for ex vivo production of progenitor cells, but whether expansion will speed engraftment and improve outcome after UCB remains to be determined. UCB is known to contain extremely immature stem cells. Consequently, such pluripotent or, perhaps, multipotent stem cells have been proposed as elements suitable for cellular therapy and regenerative medicine. Up to date there are no conclusive data regarding these possibilities but preliminary in vitro and animal studies in the field of tissue regeneration suggest some degree of plasticity and/or transdifferentiation. UCB cells are showing their unique qualities and potential, and consequently UCB banks might dramatically increase the scope of their clinical application.

Within the whole world container traffic, the largest share of containers is in the status of repositioning. Container repositioning results from the need for harmonization between the point of empty container accumulation and the point of demand, and waiting time for the availability of the first next transport of cargo. This status of containers on the container market is the consequence of imbalances in the worldwide trade distribution on most important shipping routes. The need for fast and effective reallocation of empty containers causes high costs and often represents an obstacle affecting the efficiency of port container terminals and inland carriers.In accordance with the above issue, this paper is mainly focused on the analysis of the data concerning global container capacities and the roots of container equipment imbalances, with the aim of determining the importance of empty container management and the need for empty container micro-logistic planning at the spread port area.

BACKGROUND/AIMS: Human echinococcosis is endemic in some areas of the world, including Mediterranean countries. The liver is the most frequent seat of echinococcosis, involved in about 70% of cases. Because there is still no effective medical therapy, surgery remains the treatment of choice. METHODOLOGY: Twenty-seven patients operated on for liver hydatid disease between 1990 and 1995 were analyzed and compared with results obtained from a study undertaken at our clinic between 1960 and 1988. RESULTS: The diagnosis was established by typical case history, clinical features and laboratory tests, of which imaging methods proved most informative. Radical procedures (total pericystectomy and liver resection) seem to be too aggressive for treatment. Marsupialization and drainage were mostly abandoned, because of high morbidity rates. CONCLUSIONS: Among surgical procedures used at our clinic, evacuation of the cyst with partial excision of the pericyst and omentoplasty resulted in the lowest morbidity and, thereupon, the shortest post-operative hospital stay and the best clinical results.

EPIDEMIOLOGY: Aging is a natural process and a part of our lives, but nowadays there is an increase in the number of persons aged 65 and over. Today infectious diseases are still responsible for one-third of all deaths in the world. The elderly population is most vulnerable to serious infections and at greatest risk for death and complications. Among geriatric population pneumonia and influenza are the fourth most common cause of death. VACCINATION: One of the goals of preventive medicine is to reduce the rate of complications and mortality from infectious diseases by increasing immunization rates. Influenza and pneumococcal vaccines are indicated for persons aged 65 and over. Despite well-recognized benefit of such vaccination, less than 50% of eligible patients receive the vaccine each year. INFECTIONS: Older persons generally have increased susceptibility to infections because of multiple risk factors and they are the most vulnerable population to nosocomial and health-care associated infections. Older persons may manifest infectious diseases atypically, with acute confusion or delirium which can lead into delay in diagnosis and therapy. It is important to know that the older present with delayed or poor response to antimicrobial therapy and high rates of adverse reactions to drugs, including antibiotics. CONCLUSION: As elderly population is rapidly growing, majority of patients with serious or life-threatening infections are old. Geriatric issues have not typically been a focus of training in infectious diseases, but we must become aware of and knowledgeable about special and unique aspects of infections in this population.

Nadzor korištenja antimikrobnih lijekova (engl. antimicrobial stewardship) strategija je koja obuhvaća međusobno povezane postupke za poticanje njihovog odgovornog korištenja. Može ju primjeniti pojedinac ali je primjenjiva i na svjetskoj razini, u humanoj medicini, veterini i očuvanju okoliša. Pridržavanjem tih mjera osigurava se ispravna i odgovorna primjena antimikrobnih lijekova čiji je cilj produženje njihovog vijeka, usporavanje razvoja otpornosti (rezistencije) mikroorganizama, smanjenje morbiditeta od infekcija uzrokovanih višestrukootpornim (multiplorezistentnim) mikroorganizmima i smanjenje troškova. Različite međunarodne organizacije odredile su zadatke i dužnosti vezane uz odgovarajuću primjenu antimikrobnih lijekova.

Transplantation is a definitive treatment option for patients with end-stage liver disease, and for some patients with acute liver failure, hepatocellular carcinoma or end-stage renal disease. Long-term post-transplantation complications have become an important medical issue, and cardiovascular diseases (CVD) are now the leading cause of mortality in liver or kidney transplant recipients. The increased prevalence of metabolic syndrome (MS) likely plays a role in the high incidence of post-transplantation CVD. MS and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), are prevalent among the general population and in pre- and post-transplantation settings. MS components are associated with recurrent or de novo NAFLD in transplant recipients, potentially influencing post-transplantation survival. Moreover, recent data reveal an important association between NAFLD and risk of incident of chronic kidney disease (CKD). Therefore, NAFLD identification could represent an additional clinical feature for improving the stratification of liver and kidney transplant recipients with regards to risks of CVD, CKD and renal allograft dysfunction. All MS components are potentially modifiable; therefore, it is crucial that hepatologists, nephrologists and primary care physicians become more engaged in managing post-transplantation metabolic complications. The present review discusses the recent clinical evidence regarding the importance of MS and its components after liver and kidney transplantation, as well as the link between MS and NAFLD after liver and kidney transplantation.