Correlation of ex vivo cytokine secretion profiles with scoring indices in ulcerative colitis.

BACKGROUND: In ulcerative colitis, the complexity of mucosal cytokine secretion profiles and how they correlate with endoscopic and clinical scores is still unclear. METHODS: In this study, we collected fresh biopsies from UC patients to investigate which cytokines are produced in ex vivo culture conditions, a platform increasingly used for testing of novel drugs. Then, we correlated cytokine production with several scoring indices commonly used to assess the severity of the disease. RESULTS: Increased levels of IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNFα and IFNÉ£ were produced by biopsies of UC patients compared to non-IBD controls. Our results show a better correlation of cytokine levels with Mayo Endoscopic Subscore (MES) and Mayo score, than the more complex Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Out of 10 measured cytokines, eight correlated with MES, six with Mayo score and only three with UCEIS, due to the partial increase in cytokine secretion observed in donors with UCEIS = 7-8. When we analysed individual subscores within the UCEIS, Vascular Network subscore showed a correlation similar to MES (7/10 cytokines), while Bleeding as well as Erosions and Ulcers subscores correlated with only 3/10 cytokines, similarly to the total UCEIS. CONCLUSIONS: Our findings suggest that choosing biopsies from donors with MES = 2-3 and UCEIS = 2-6 from areas with no bleeding and no superficial and/or deep ulcers could enable a deeper insight into the cytokine profile of the inflamed tissue and represent a better tool for studying potential therapeutic targets and evaluation of novel therapies.

Immunosenescence, Inflammaging and Resilience: An Evolutionary Perspective of Adaptation in the Light of COVID-19 Pandemic.

The evolution of immunology enabled the study of role of innate and adaptive immunity in systems biology network of immunosenescence and inflammaging. Due to global reduction in birth rates and reduced mortality, in year 2025 there will be about 1.2 billion of people over age of sixty, worldwide. The notion that the real age is not chronological, but the biological one led to the concept of "bioage", defining the biologic reactivity and resilience, including the immune competence of an individual. A competent immune network, systemic and mucosal is intrinsic to resilience and homeostasis of the human holobiont as the unit of evolution. In elderly, the immunosenescence could be associated with higher levels of proinflammatory mediators (such as IL-6), frialty and mortality. Proi-inflammatory state in elderly is denoted as inflammaging, characterized with low-grade (sterile) inflammation, as a physiologic response to life-long antigenic stimuli. When under control, inflammaging could be regarded as an efficient defense mechanism, oposed and regulated by anti-inflammatory pathways and molecules. Immunosensecence. The emerging concepts of "individual immunobiography" and "trained immunity" speak in favour that the immunological experience during the life would shape the ability of each individual to respond to various stimuli, strongly influencing the elements of innate and adaptive immunity, including macrophages and innate lymphoid cells. Older age is one of the main risk factors for the severe clinical picture and adverse outcome of COVID-19 infection, due to immunosenscence and chronic low-grade inflammation (inflammaging), both characterizing the immune reactioin in elderly. The senescent immune system, along with the advanced process of inflammaging is prone to react with uncontrolled activation of innate immune response that leads to cytokine release syndrome, tissue damage and adverse outcome of infection. Further research is aimed to nutritional and pharmacologic (immunomodulatory) interventions to influence the process of bioaging and immunosenscence, and to modulate the reaction of elderly to infection, including the COVID-19.

[Croatian guidelines for gastric cancer prevention by eradication of Helicobacter pylori infection]. / Hrvatski postupnik za prevenciju zelucanog raka eradikacijom infekcije Helicobacterom pylori.

Gastric cancer is the fourth most common type of cancer and the second leading cause of cancer-related death in the world. Although gastric cancer has a multifactorial etiology, infection with Helicobacter pylori is highly associated with gastric carcinogenesis. Carcinogenesis is also influenced by some environmental factors and host genetic diversity, which engenders differential host inflammatory responses that can influence clinical outcome. Chronic gastritis induced by H. pylori is the strongest known risk factor for adenocarcinoma of the distal stomach, but the effects of bacterial eradication on carcinogenesis have remained unclear up to now. Although eradication of H. pylori infection appears to reduce the risk of gastric cancer, several recent controlled interventional trials by H. pylori eradication to prevent gastric cancer have yielded disappointing results. To clarify this problem in a high-risk population, the investigators conducted a prospective, randomized, double-blind, placebo-controlled, population-based studies. The results of previous studies highlight the importance of longer and careful follow-up after eradication therapy. It seems that eradication treatment is effective in preventing gastric cancer if it is given before preneoplastic conditions/lesions, gastric atrophy, metaplasia, and dysplasia, have had time to develop. Furthermore, the significant efficacy of treatment observed in younger patients suggests the need to eradicate H. pylori as early as possible. This consensus aimed to propose guidelines for the diagnosis, management and control of individuals with chronic gastritis, atrophy, intestinal metaplasia, or dysplasia.

[The role of anti-TNF therapy in ulcerative colitis]. / Mjesto anti-TNF terapije u lijecenju ulceroznog kolitisa.

Anti-TNF-alfa molecules are currently being used to treat ulcerative colitis regarding to the fact that TNF-alpha has an important role in the pathogenesis of IBD. Although these drugs improved the therapy of patients, immunogenicity limits their potential for clinical use. Infliximab and adalimumab are effective for induction and maintenance of remission in outpatients with moderate to severe steroid-refractory ulcerative colitis. Biologics can be a drug of choice for patients with refractory proctitis and refractory pouchitis. In hospitalized patients with steroid-resistant severe ulcerative colitis who are candidates for colectomy, infliximab may be second-line option. Adequate long-term maintenance therapy with anti-TNF is required after rescue therapy for a sustained benefit. Regarding to the known risk for side-effects of anti-TNF drugs especially in patients concomitantly treated with thiopurines it is urgent future research.

Claudins: Beyond Tight Junctions in Human IBD and Murine Models.

Claudins are transmembrane proteins constituting one of three tight junction protein families. In patients with inflammatory bowel disease (IBD), disease activity-dependent changes in expression of certain claudins have been noted, thus making certain claudin family members potential therapy targets. A study was undertaken with the aim of exploring expression of claudins in human disease and two different animal models of IBD: dextrane sulfate sodium-induced colitis and adoptive transfer model of colitis. The expression of sealing claudin-1, claudin-3, claudin-4, and claudin-8, and pore-forming claudin-2 in humans and rodents has been evaluated by immunohistochemistry and quantitative polymerase chain reaction. Claudins were expressed by epithelial and cells of mesodermal origin and were found to be situated at the membrane, within the cytoplasm, or within the nuclei. Claudin expression by human mononuclear cells isolated from lamina propria has been confirmed by Western blot and flow cytometry. The claudin expression pattern in uninflamed and inflamed colon varied between species and murine strains. In IBD and both animal models, diverse alterations in claudin expression by epithelial and inflammatory cells were recorded. Tissue mRNA levels for each studied claudin reflected changes within cell lineage and, at the same time, mirrored the ratio between various cell types. Based on the results of the study, it can be concluded that 1) claudins are not expressed exclusively by epithelial cells, but by certain types of cells of mesodermal origin as well; 2) changes in the claudin mRNA level should be interpreted in the context of overall tissue alterations; and 3) both IBD animal models that were analyzed can be used for investigating claudins as a therapy target, respecting their similarities and differences highlighted in this study.

Informed consent for gastrointestinal endoscopy: a view of endoscopists in Croatia.

BACKGROUND/AIM: There are many differences and deficiencies in the process of informed consent. The aim of this study was to get the view of gastrointestinal endoscopists in Croatia on obtaining patients' consent before endoscopic procedures. METHODS: During the 2004 annual meeting of the Croatian Society of Gastroenterology, endoscopists were asked to answer a questionnaire according to common clinical practice in affiliated institutions. It included questions on endoscopists' experience and education in medical ethics, as well as on the nature and quality of information given to patients and their opinion on proposed measures for improvement of the informed consent process. RESULTS: The questionnaire was distributed to 96 endoscopists attending the meeting and the response rate was 54% (52/96). In only 50% of institutions was the obtained consent written and potential complications of endoscopic procedures are occasionally given to the patient. In the minority of cases the patient is provided with information about alternative diagnostic tests and/or treatment options, and the information about mortality rate was almost never discussed. CONCLUSIONS: In Croatia, the process of informed consent for endoscopy needs improvement and should be regarded against the background of education in medical ethics, regional burden in endoscopic practice and appropriateness of by-laws and local guidelines.

[Obesity--a global public health problem]. / Pretilost--globalni javnozdravstveni problem.

Obesity and overweight, as a part of the metabolic syndrome, are well known risk factors for the development of diabetes, hypertension, coronary heart disease, hyperlipidemia, stroke, sleep apnea syndrome, osteoarthritis and certain forms of cancer. Cardiovascular disease remains the leading killer in industrialized countries, where it accounts for 40% of deaths. Obesity is defined either by increased waist circumference, waist to hip ratio, or body mass index. Obesity results from an interaction of genes and lifestyle. As people in both developed and developing countries eat more and more energy dense food, and have ever less physical activity, the number of overweight and obese people increases to epidemic proportions. Abdominal obesity plays a key role in the pathophysiology of metabolic disorders, is associated with insulin resistance, and predicts the development of type 2 diabetes and subsequent coronary artery disease. In the general population, obesity is associated with an increased mortality, but paradoxically, a positive correlation between body mass index and survival in congestive heart failure has been reported. In secondary prevention, obesity is underrecognized, underdiagnosed and undertreated in persons with cardiovascular diseases. Weight loss and prevention of weight gain have to be considered one of the most important strategies to reduce the incidence of cardiovascular disease. Increased physical activity and appropriate diet are the cornestones of treatment. Considering the high prevalence of overweight and obesity in Croatia, there is urgent necessity to improve the level of knowledge and skills in understanding obesity by health care services, and to implement appropriate professional strategy to achieve the desired lifestyle modifications.

[Erectile dysfunction and cardiovascular disease]. / Erektilna disfunkcija u kardiovaskularnih bolesnika.

Erectile dysfunction (ED) is a highly prevalent disorder worldwide. ED and cardiovascular disease (CVD) share many risk factors, the former often being the presenting symptom. The knowledge of the relationship between CVD and ED, the cardiovascular implications of phosphodiesterase type 5 inhibitors for the treatment of ED can help improve the quality of life of patients with both conditions. Cardiologists have a prominent role in treating ED.

[Specific characteristics of hypertension in postmenopausal women]. / Posebnosti arterijske hipertenzije zena u postmenopauzi.

Sex-specific differences in the incidence of cardiovascular diseases have long been known, and estrogens have been considered responsible for this dissimilarity. After the menopause, the consequences of hypertension in women change. Their risks of myocardial infarction and stroke rise, which has in part been ascribed to the loss of estrogen and onset of menopausal metabolic syndrome. Sex differences in the components of the renin-angiotensin system have been shown to exist, and may play a central role in the blood pressure control. Hypertensive menopausal women do not receive optimal treatment. They have poorer prognosis than men of the same age. Therefore, their antihypertensive management calls for special attention.

[The role of endoscopic ultrasound in digestive tract diseases in era of advanced techniques of computed tomography]. / Uloga endoskopskog ultrazvuka u bolestima probavnog sustava u eri naprednih tehnika kompjutorizirane tomografije.

During the last 20 years endoscopic ultrasound (EUS) has been established as a highly accurate method in the diagnosis of digestive tract diseases. This method enables analysis of the lesions within the bowel wall, pancreas, and biliary system with utmost precision. Good results have also been achieved in evaluation of regional lymphadenopathy in staging of malignant diseases. Principal limitations of this method originate from its low accesibility and technical complexity which requires well trained sinologist and scientific evaluation of results in order to achieve adequate level of skill. Complications occur rarely with numbers comparable to other endoscopic procedures. With new software and hardware device introduced, computerized tomography (CT) (this refers in the first place to multidetector row CT) has been tremendously upgraded approaching the EUS in diagnostic accuracy in mentioned indications, and overcoming it in detection of distant metastases. Implementation of 3D reconstruction techniques allowed CT to enter the area of classic endoscopy, as in the case of virtual gastroscopy and/or colonoscopy. CT is a noninvasive method, very acceptable to majority of patients, and therefore popular and more prevalent compared to EUS. Although comparable in diagnostic accuracy in majority of indications, endosonography retains advance in evaluation of lesions within GI tract wall (including the early stages of carcinoma), detection of small biliary stones and small pancreatic tumors. Moreover, EUS is indespensable in therapeutic indications. Experiences with fine needle aspiration, punctions and drainage of cysts and abscesses, celiac plexus neurolysis and creation of digestive anastomosis confirm its place and value among the minimally invasive procedures which minimize the need for surgical intervention, patients' trauma and treatment costs.

Effect of educational programs on asthma control and quality of life in adult asthma patients.

This study investigated the effectiveness of different educational programs in obtaining better asthma control and asthma-related quality of life (QoL). In 60 adult patients with moderate persistent asthma we tested the benefit of individual verbal instructions (IVI), written information ("asthma booklet", B), and integrated asthma classes ("asthma school", AS). At the enrollment and at the end of the study, all participants completed the questionnaires regarding their asthma-related knowledge (ArK) and QoL. During the 12-week period all patients recorded their asthma symptoms, morning and evening peek expiratory flow rates (PEFR), and the use of rescue medication. AS and IVI groups showed a significantly greater improvement in QoL than the B group. AS group obtained the highest ArK but no difference in the level of improvement among the groups has been documented. The improved average asthma symptom score and decreased utilization of the rescue medication were documented in all groups without significant differences among them. We also found significant improvements in both morning and evening PEFR in IVI group as well as in the morning PEFR in AS group. We conclude that among tested educational interventions the AS caused the best improvement in QoL while IVI produced the best overall response in both parameters of the asthma control and QoL.

[Doxycycline induced esophageal ulcers: report of two cases and review of the literature]. / Vrijedovi jednjaka prouzroceni doksiciklinom: prikaz dvaju bolesnika i pregled literature.

Doxycycline-induced esophageal ulcers (DIEU) are rarely observed in endoscopy units. On the other hand doxycycline itself has been claimed as an offending drug in 1/4 out of about 1000 cases of drug induced esophageal ulcers reported in the literature so far. In this article we present two patients with typical history and endoscopic features of esophageal ulcers as an consequence of doxycycline therapy. The therapy consisted of doxycycline withdrawal along with treatment with proton pump inhibitors and sucralfate which had led to disappearance of chest discomfort within one week period. Fourteen days of the tratment beginning complete recovery of the mucosal defects has occurred in both patients. In conclusion, in case of chest pain and painful swallowing occurring in a person who takes doxycycline, DIEU has to be considered followed by the esophagoscopy which would confirm clinical suspicious with high specificity leading to correct diagnosis and treatment of this condition.

Sonography in diagnosis and follow-up of serosal eosinophilic gastroenteritis treated with corticosteroid.

An 18-year-old patient presented with abdominal pain, nausea, and low-grade fever. Sonography showed ascites in the region of the terminal ileum, and the presence of peritoneal nodules suggested peritoneal inflammation. Cytologic analysis of ascites revealed numerous eosinophils. Sonographic visualization of nodular peritoneal deposits associated with eosinophilic ascites permitted the diagnosis of the serosal form of eosinophilic gastroenteritis. The absence of mucosal and muscular involvement in the bowel wall was confirmed by endoscopy and CT. Two weeks of 20 mg/day oral prednisolone led to relief of the patient's symptoms, with normalization of laboratory parameters and sonographic findings.