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Etrasimod, a novel selective sphingosine-1-phosphate receptor modulator, was recently approved by the U.S. Food and Drug Administration and the European Medicinal Agency for the treatment of moderately to severely active ulcerative colitis in adults. In this research, the forced degradation study as an integral part of drug product and packaging development, which generates data on degradation mechanisms, is published. The development and validation of the stability-indicating method using a superior high-performance liquid chromatography technique coupled with a diode array detector and tandem mass spectrometer was performed to support the forced degradation study and monitor the formation of degradation products. Etrasimod demonstrated good stability under elevated temperature and basic stress conditions, while acidic hydrolysis, oxidative, and photolytic degradation produced eight degradation products. The knowledge of degradation products will be useful in the long-term stability study for establishing the acceptance criteria of etrasimod as a drug substance and dosage form during quality control and stability assessment. The eco-friendliness of the developed forced degradation procedure was evaluated using various greenness appraisal tools. The green metric tools showed that the forced degradation procedure obeys eco-friendly conditions.

Anemija zbog manjka željeza ili sideropenična anemija najčešći je oblik anemije u populaciji. Sideropenična anemija može nastati uslijed gastrointestinalnih bolesti, ginekoloških i drugih kroničnih krvarenja, može biti dio kliničke slike nefroloških i drugih bolesti i stanja, može doprinositi srčanom zatajenju u kardioloških bolesnika te pogoršavati ishode operativnih zahvata. Zbog navedenoga potreban je timski rad u liječenju sideropenične anemije, važno je otkriti i liječiti uzrok koji je doveo do gubitka željeza te liječiti anemiju nadoknadom željeza. Cilj je ovog rada prikazati pregled literature i klinička iskustva različitih nehematoloških specijalističkih usmjerenja u liječenju sideropenične anemije parenteralnim pripravcima željeza u različitim tercijarnim centrima u Hrvatskoj. U radu su opisani pristupi i postupnici u zbrinjavanju sideropenije i sideropenične anemije parenteralnim željezom iz aspekta gastroenterologa, ginekologa, nefrologa, kardiologa te anesteziologa, sa specifičnostima pojedinih bolesti i pristupa njihovom liječenju. U zaključku, novi visokodozni pripravci parenteralnog željeza unaprijedili su mogućnosti liječenja sideropenične anemije i primjenjuju se sve više u dnevnim bolnicama i odjelima različitih struka u Hrvatskoj, a ne samo u hematološkim dnevnim bolnicama ili odjelima.

Background/Objectives: The phyla Firmicutes and Bacteroidetes are the main constituents of the gut microbiota. An imbalance in the gut microbiota is a sign of dysbiosis, and the Firmicutes-to-Bacteroidetes ratio has been proposed to be a marker of it, especially in the context of obesity. Since Croatia is the country with one of the highest obesity rates in Europe, a pilot observational study was conducted. The aim of the study was to investigate the validity of this potential biomarker in a methodological study using sample processing, DNA sequence analysis and characterization of recruited participants, including various health factors. Methods: A study involving Croatian population was conducted. Participants age, body weight, gender, health history and lifestyle factors were recorded. Gut microbiota composition was analyzed using 16S rRNA sequencing. The F/B ratio was calculated and evaluated in the context of health factors. Statistical analysis was performed to detect the possible association of F/B ratio and excess body weight (kg) and possible impact of certain lifestyle factors. Results: No association between the F/B ratio and excess body weight (kg) was found. Excess body weight was significantly associated with higher age, male gender, and history of appendectomy. No significant health predictors of the F/B ratio were found, but weight gain was positively associated with a higher average F/B ratio. Conclusions: Although this study could not confirm the predictive value of the F/B ratio or any other phyla-related biomarker for excess body weight in the study population, it demonstrated interesting insights into the obesity-associated gut microbiota.

Background: Childhood obesity is a global public health concern. Development of effective public health interventions represents the only viable option for decreasing the prevalence of childhood obesity. The objective of this study was to assess the effectiveness of a school-based “PETICA—Play for Health” obesity prevention program in urban and rural areas in Croatia. Methods: This before-and-after study included 28 elementary schools in Croatia focused on pupils (n = 753, 2nd grade) and their guardians (n = 753) during the school year 2022/2023. “PETICA” multicomponent lessons and workshops (10) were implemented in the school curriculum and home settings (parents) as part of the intervention. Knowledge and lifestyle habit changes were evaluated via the questionnaire on knowledge and habits regarding nutrition and physical activity pre-/post-education. The Wilcoxon test for paired samples, Student’s t-test (dependent and independent samples), multiple Mann Whitney U tests (p < 0.05), Spearman’s correlation, and heatmaps were used. Results: The analysis showed a significant increase in acquired knowledge among pupils (both settings) and habits in the rural setting (increase in sports activities participation, breakfast, and vegetables consumption (p < 0.001, p = 0.003, p = 0.004)), decrease of sweets and salty snacks intake (p = 0.027, p = 0.011), and also, the link between parents’ and children’s physical activity levels (p = 0.028 vs. p = 0.022), emphasizing the importance of parents as healthy lifestyle role-models. Conclusion: The study shows that “PETICA” is an efficient school-based educational model that contributes to positive changes in children’s knowledge and lifestyle habits that are a prerequisite for childhood obesity prevention.

Pravilna prehrana iznimno je važna u prevenciji šećerne bolesti i regulaciji glikemije. Šećerna bolest ubraja se u kategoriju bolesti koje se uspješno mogu prevenirati, dobro liječiti te im se može spriječiti ili odgoditi razvoj kroničnih komplikacija. Edukacija o pravilnoj prehrani treba biti individualno prilagođena, pri čemu treba obratiti pozornost na dob bolesnika, način života, socioekonomski status, tjelesnu aktivnost i komplikacije vezane uz šećernu bolest. Kod šećerne bolesti promjena životnih navika, što uključuje pravilnu prehranu, redovitu tjelesnu aktivnost i regulaciju tjelesne mase, može uvelike pridonijeti regulaciji glikemije, a u tipu 2 u nekim slučajevima može dovesti i do njene remisije. Smjernice su rezultat suradnje zdravstvenih stručnjaka koji sudjeluju u liječenju i edukaciji osoba koje boluju od šećerne bolesti. Utemeljene su na dokazima, prema metodologiji GRADE (engl. grading of recommendations, assessment, development and evaluation) koja uz snagu dokaza opisuje i razinu preporuke. Temeljni zaključci ovih smjernica odnose se na procjenu nutritivnih potreba te primjenu medicinske nutritivne terapije, individualno prilagođene osobama sa šećernom bolešću kao i onima koji imaju i neke od vezanih komorbiditeta.

Hypophosphatemia as a side effect of parenteral iron administration has been well described in the recent literature. However clear protocols or recommendations for prevention, timely recognition and treatment are not available. Different data on risk factors in patients with inflammatory bowel disease (IBD) according to the published papers further complicate the understanding of hypophosphatemia and long-term complications, and thus the necessary steps in an adequate approach to prevention and treatment. By presenting a series of clinical cases of four IBD patients, we want to show the heterogeneity of the clinical presentation of hypophosphatemia, the influence of nutritional, inflammatory and other factors and also possible treatment modalities. Furthermore, we want to point out which group of IBD patients is at additional risk of developing hypophoshatemia, with the aim of timely diagnosis and treatment initiation.

Objectives Faecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. The aim of this study was to establish the value of faecal calprotectin concentration as a predictor of remission in ulcerative colitis and its correlation with laboratory, endoscopic and clinical findings.Methods The single centre study included 126 adult patients with established diagnosis of ulcerative colitis consecutively visiting our Day clinic from March 2017 to March 2019. We measured serum biomarkers- CRP, haemoglobin, leukocytes and platelets. Faecal calprotectin was determined from stool, and endoscopy was performed with calculation of MAYO endoscopic subscore system (MES 0–1: remission, and MES 2–3: active disease). Clinical assessment was done by using Mayo score for ulcerative colitis (clinical Mayo score 5: active disease).The statistical analysis was performed using an univariate and multivariate model of disease remission prediction using logistic regression.Results According to univariate analysis the increase of faecal calprotectin concentration by 10 ug/g is associated with an 8% decrease in probability of disease remission (OR 0.9921, p

Eosinophilic esophagitis is a chronic, Th2-mediated disease characterized by the presence of predominantly eosinophilic inflammation in the esophagus. The disease is mediated by an immune or antigenic pathophysiological background, and the definition of the disease requires the presence of clinical symptoms and histological elements of the disease. Over the past ten years, there has been an increase in the incidence and prevalence of EoE, where the prevalence of EoE varies, and in the general population is 0.2–4 / 1000 in asymptomatic patients, while in symptomatic patients it is 5–6%. The prevalence in the general population is considered to be 43 to 52/100000. Pathophysiologically, it is a polygenic disease in which certain cytokines (IL-4, IL-5, IL-13, IL-14 and TGF-β) play a key role by activating eotaxin-3 in the esophageal mucosa. Eotaxin-3 strongly attracts eosinophils into the esophageal mucosa, and thus activated eosinophils lead to the attraction of other inflammatory cells, the release of mediators and the onset of disease. The histological criterion for the diagnosis of EoE is the presence of more than 15 eosinophils present in the visual field of esophageal mucosal biopsies. Clinically, the disease can manifest itself by a spectrum of symptoms, from acute food impaction, dysphagia, epigastric pain and heartburn, and nonspecific symptoms such as incontinence or vomiting also occur in these patients. The basis of treatment of these patients is based on drug therapy, dietary recommendations and endoscopic dilatation. Thea im of these clinical recommendations is to present the pathway of diagnosis and therapy of eosinophilic esophagitis.

Abstract Several biologic treatments are available in addition to intravenous also in subcutaneous form for treatment of chronic diseases. Benefits of the subcutaneous application of drugs include self-administration by the patient, shorter time of application process with less infusion related adverse events and consequently lower healthcare costs. With appropriate education and support patients are able to administer their treatments at home. This leads to improvement of quality of life, reduction of time needed to travel to the healthcare institution and consequently also reduces costs also for the patient. Over one million residents in the USA and 2.5 million in Europe are estimated to have inflammatory bowel disease (IBD), with substantial costs for health care. These estimates do not factor in the ‘real’ price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients. The Virtual Community Meeting, which offered an exchange of experience and opinions from healthcare professionals who are active in treating IBD, and patients with this chronic disease, revealed in-depth arguments and answers to some essential questions: which patients prefer subcutaneous over intravenous dosing; which patients continue to favour intravenous infusions; what are the limitations regarding both applications; what is the patient’s role in therapeutical decision-making and how does IBD affect the patient’s work, finances and quality of life? The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from the health-economic, scientific, and personal perspectives. The meeting offered strong confirmation that most of the patients and healthcare professionals prefer subcutaneous over intravenous drug administration but emphasise the management of risks associated with treatment compliance. Patient education provided by the IBD team in this regard is mandatory. Quality of life of patients is poorer during active disease, but the findings that it can improve over time, including as a result of home- or self-administration of biologics, may be encouraging for individuals with this chronic disease.

The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD (Crohn’s disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing. Mucosa was sampled at six positions, from terminal ileum to rectum. We demonstrate that mucosal microbiota is spatially homogeneous, cannot be differentiated based on the local inflammation status and yet provides bacterial footprints superior to fecal in discriminating disease phenotypes. IBD groups showed decreased bacterial diversity in mucosa at all taxonomic levels compared to IBS. In CD and UC, Dialister was significantly increased, and expansion of Haemophilus and Propionibacterium characterized UC. Compared to healthy individuals, fecal microbiota of IBD and IBS patients had increased abundance of Proteobacteria, Enterobacteriaceae, in particular. Shift toward reduction of Adlercreutzia and butyrate-producing taxa was found in feces of IBD patients. Microbiota alterations detected in newly diagnosed treatment-naïve adult patients indicate that the microbiota changes are set and detectable at the disease onset and likely have a discerning role in IBD pathophysiology. Our results justify further investigation of the taxa discriminating between disease groups, such as H. parainfluenzae, R. gnavus, Turicibacteriaceae, Dialister, and Adlercreutzia as potential biomarkers of the disease.

Esophageal manometry is one of the main axes in diagnostic armamentarium that deals with esophageal motility disorders, next to endoscopic and radiological methods. Traditional, conventional manometry, has greatly been replaced by a modern technique, high resolution manometry which enables not only better spatiotemporal signal resolution and compatibility, but also shortens the time of the procedure which is extremely important for patients undergoing it. Two catheters are being used, solid state and water perfused. Both record pressures within the esophageal lumen and both esophageal sphincters. Contemporary technology has also enabled incorporation of impedance sensors into the catheter. Impedance is based on resistance changes to liquid or food boluses.These changes help in bolus transit evaluation, reducing the need for ionization procedures. Each examined bolus (liquid or solid) is evaluated according to Chicago classification criteria and parameters that are within these criteria. According to the third version of the Classification, functional esophageal disorders are divided into EGJ outflow obstruction disorders, major peristaltic and minor peristaltic disorders. Introduction of this methodology, but also the continuous update of Chicago classification, help in timely diagnosis and further treatment of all the more frequently diagnosed functional esophageal disorders

Refeeding syndrome (RFS) is a serious and potentially fatal complication that occurs in patients with severe malnutrition of various etiologies after repeated, uncontrolled introduction of a diet, especially carbohydrates. Complications of RFS develop due to rapid metabolic changes that occur during the switch from catabolism to anabolism, and cellular depletion of phosphorus, potassium, magnesium and micronutrients, and can affect one or more organ systems. Most of RFS complications associated with vitamin deficiency are related to thiamine deficiency. Due to its coenzyme role in the metabolism of carbohydrates and branched chain amino acids, thiamine is an important factor in maintaining the normal function primarily of cerebral energy metabolism. Understanding the basic biochemistry during starvation, and consequently the mechanisms and factors influencing metabolic changes during RFS, is important for timely identification of patients at risk and prevention of RFS and also many clinical complications it can cause regardless of nutritional support modality.

Inflammatory bowel diseases (IBD) usually affect women in their fertile years and, therefore, have implications for their fertility and pregnancy. The presence of IBD during pregnancy has been shown to adversely affect pregnancy outcomes, and increased rates of preterm delivery and of spontaneous abortion have been reported. An onset of acute severe colitis in pregnancy has rarely been seen. We present the case of a 42-year-old woman who conceived after 9 attempts of in vitro fertilization and whose pregnancy was the result of a donated oocyte. Shortly after conception, she was diagnosed with severe active ulcerative colitis, and biologic therapy was introduced in the 28th week of pregnancy. Although therapy for IBD in pregnancy is considered safe for most drugs, this was not very well known in 2015. We also consider our case exceptional because we now have a 5-year follow-up of our patient and her child after having begun biologic therapy during late pregnancy.

Inflammatory bowel disease (IBD) patients with vitamin D deficiency show an increased risk of hospital admission, surgery, and loss of response to biologic therapy while high vitamin D levels are identified as a protective factor. Our goal was to investigate the prevalence of untreated and undertreated vitamin D deficiency and factors associated with vitamin D deficiency. In this cross-sectional study, we measured serum vitamin D in a random sample of Caucasian IBD patients. Vitamin D deficiency was defined as

Hemangioma of the small intestine is a rare vascular malformation which mostly presents as occult gastrointestinal bleeding and iron-deficiency anemia. Patients are often asymptomatic except of fatigue due to anemia. Hemangiomas can arise anywhere in the luminal gastrointestinal tract, with jejunum as the most commonly involved site. They are very hard to recognize mostly due to their localization. Video capsule endoscopy and balloon-assisted enteroscopy have very much improved preoperative diagnostics and made major contribution to establishing the diagnosis – which was very difficult in the past and almost all cases were diagnosed during or after the operation. Surgical resection is still the conventional treatment modality, although with the improvement of endoscopic therapeutic interventions (endoscopic mucosal resection, argon-plasma coagulation) there are more therapeutic possibilities.

The Mediterranean diet (MD) and the Nordic diet (ND) share more similarities than differences. Both diets are based on typical local and seasonal foods, share similar nutritional recommendations based on plant-based dietary principles, and are both now orienting toward environmental protection and sustainability. The main difference between the two diets is the primary fat source. Olive oil is the synonym for MD while the ND uses more rapeseed/canola oil. While longitudinal epidemiological studies support adherence to MD as a way to prevent chronic diseases, ND still needs more such studies because the current results are discrepant. Notably, studies that assessed the association between both diets and lower risks of chronic diseases, disability, and mortality from specific and all causes, implied that ND could also have an advantageous effect as MD. Hopefully, there will be more longitudinal and large prospective studies in the future that will provide more evidence-based recommendations.

Purpose: Chronic inflammatory diseases are related with earlier onset of atherosclerosis. We hypothesized that inflammatory bowel disease patients with chronic, systemic inflammation have an increased arterial stiffness associated with the disease duration. Also, we wanted to compare arterial stiffness markers between inflammatory bowel disease and well-controlled hypertension patients. Materials and methods: A total of 89 inflammatory bowel disease patients (60 patients with Crohn’s disease and 29 patients with ulcerative colitis, age range 20–64 years) without history of arterial hypertension or diabetes were enrolled and age matched with a control group of patients (73 patients, age range 25–69 years, 41 (56.1%) males) with known history of well-controlled arterial hypertension. We have used a noninvasive device that simultaneously measures brachial blood pressure and estimates PWV and AIx in inflammatory bowel disease and hypertension groups of patients. Results: Patients with pathological PWV values were significantly older, had significantly longer duration of inflammatory bowel disease, higher values of serum cholesterol and HDL-cholesterol, and higher AIx (17.4% vs. 9.8%) (all p

Inflammatory bowel diseases are a group of chronic inflammatory conditions that affect gastrointestinal tract due to inapt and continuous immune activation in response to a myriad of predisposing factors (most notably genetics, environmental impact and gut microbiota composition). It has been shown that vitamin D status can also play a role in the disease pathogenesis, as its deficiency is commonly observed in two major forms of inflammatory bowel diseases – Crohn’s disease and ulcerative colitis. Mounting evidence supports the concept of intricate relationship between gut dysbiosis and vitamin D metabolism, while suboptimal levels of this vitamin have been linked to increased clinical disease relapse rates, inadequate response to drugs, as well as decreased quality of life in patients with Crohn’s disease and ulcerative colitis. Consequently, the pertinent question is whether increased vitamin D supplementation and (on a population level) food fortification may bring significant benefit to the affected individuals. In this short review we discuss the synthesis, functions, status and food sources of vitamin D, appraise biotechnological facets of vitamin D status analysis and food fortification, and concentrate on novel developments in the field that describe its influence on intestinal microbiota and inflammatory bowel disease.

Population aging is a global demographic trend showing continuous growth and among its consequences is a rise in malnutrition that is characteristic for the elderly. The objective of this study was to evaluate nutritional status of elderly home care patients immediately after hospital discharge and to determine factors that affect nutritional status using questionnaires based on validated tools (NRS-2002, DETERMINE checklist) and basic medical history data. The study involved 76 elderly individuals (51.3% of them older than 70) living in the City of Zagreb. The nutritional status assessment using the NRS-2002 tool showed that 57.6% of the subjects were at nutritional risk. The findings of the assessment by use of the DETERMINE tool were also unfavorable, indicating that 82.1% of persons older than 70 were categorized as being at a high nutritional risk, while 17.9% were at moderate risk. The DETERMINE checklist elements (illness; reduced intake of fruits, vegetables or dairy products; alcohol consumption; oral health problems; and weight loss) were linked to a higher NRS score. The mean number of hospital days in subjects at nutritional risk was 14.27 (the mean number in the Republic of Croatia is 8.56 days). Although the study involved a small number of subjects, the results showed a substantial presence of malnutrition among the elderly. A timely ­intervention by the healthcare system and training of healthcare personnel can be a step towards achieving a better nutritional status.

Non-alcoholic fatty liver disease (NAFLD) is becoming a major health burden with increasing prevalence worldwide due to its close association with the epidemic of obesity. Currently there is no standardized pharmacological treatment, and the only proven effective therapeutic strategy is lifestyle modification, therefore it is important to determine the potential dietary targets for the prevention and treatment of NAFLD. We assessed nutritional status in 30 patients diagnosed with NAFLD using anthropometric parameters, hand grip strength, and lifestyle and dietetic parameters (physical activity, NRS2002 form and three-day food diary). The mean body mass index was 29.62±4.61 kg/m2, yielding 86.67% of obese or overweight patients. Physical activity results indicat-ed poorly active subjects. Excessive energy intake was recorded in 27.78% of patients. The mean in-take of macronutrients was as follows: 15.5% of proteins, 42.3% of carbohydrates and 42.2% of fat, with ­deficient micronutrient intake of calcium, magnesium, iron, zinc, and vitamins A, B1 and B2. The ­results showed that the quality of nutrition in study subjects was not accordant to current rec-ommendations and that they consumed a high proportion of fat, especially saturated fatty acids, along with low micronutrient intake. The results obtained might point to the importance of unbalanced diet as a contributing factor in NAFLD development.

BackgroundBody weight loss is an important feature of heart failure (HF) and tumors. It is related to both reduced survival and adverse reactions to therapy in both of these conditions. The mechanisms of body weight loss in patients with HF and tumors are considered to be similar. Yet, studies comparing those two populations are generally lacking. The aim of this study was to compare anthropometric and laboratory data, related to weight loss, between patients with chronic HF and patients with different tumors as well as control population.MethodsLaboratory and anthropometric data on 143 consecutive patients with chronic HF and malignant diseases as well as data for 20 controls were collected.ResultsPatients with HF had lower levels of C-reactive protein (CRP) and albumin compared to controls. Anthropometric measurements revealed lower body mass index (BMI), muscle strength, mid-arm circumference, and waist circumference in patients with HF compared to controls. Measurements of biceps, triceps, subscapular, and suprailiac skinfolds were also lower in HF group. Compared to solid tumor group, HF patients had lower levels of CRP and higher levels of hemoglobin. Solid tumor patients had lower values of BMI and subscapular skinfold thickness, as well as higher muscle strength compared to HF group. Finally, compared to patients with solid hematological tumors, HF group had lower levels of albumin, lower muscle strength, as well as lower mid-arm circumference.ConclusionWe found differences in anthropometric and laboratory features, related to weight loss, in patients with HF compared to control population that were expected. On the other hand, observed differences in HF group compared to patients with various tumors could imply different pathophysiological mechanisms of weight loss between those groups. Such data could serve as a cornerstone for studies with larger numbers of patients and deeper pathophysiological insight.

Abstract Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 and α4 chains of type IV collagen are expressed on the mucosal surface. We wanted to develop a biomarker reflecting early tissue injury, providing an opportunity for intervention. Two competitive enzyme-linked immunosorbent assays (ELISAs) quantifying human neutrophil elastase (HNE) degraded neo-epitopes of COL4A3 and COL4A4 were developed and investigated in two observational cohorts (n = 161, n = 100). A biomarker of MMP-mediated degradation of COL4A1 (C4M) was used for comparison. In Cohort 1, patients with mild endoscopic ulcerative colitis showed elevated levels of C4A3-HNE compared to those with severe disease. C4M had a strong positive correlation with disease activity. C4A3-HNE/C4M provided superior discrimination between mild and severe endoscopic disease and negatively correlated to disease activity. In Cohort 2, C4A4-HNE and C4A4-HNE/C4M showed similar trends. C4A3-HNE and C4A4-HNE possibly reflect early intestinal tissue injury. Combining the markers with a biomarker of another α-chain of the same collagen provides information on two distinct stages of mucosal damage. These biomarkers may be used to monitor disease flare-up in patients in remission, reducing the need for frequent endoscopic procedures.