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E. Hendrix, C. Spooren, D. Grommen, Z. Mujagic, M. Pierik, D. Jonkers

Inflammatory bowel disease (IBD) is associated with malnutrition, which can further impair disease course and quality of life. Therefore, guidelines advocate screening of patients in clinical practice. The prevalence of malnutrition in IBD-cohorts however, varies widely, mainly due to differences in parameters used. The primary aim of the present study was to assess the prevalence of malnutrition using single and a combined set of parameters (Global Leadership Initiative on Malnutrition (GLIM) criteria). Secondary aims were i) to evaluate the accuracy of screening recommendations given in current IBD guidelines and ii) to explore which patients have an increased risk of malnutrition. Malnutrition was defined by the GLIM criteria, based on the combination of a phenotypic (i.e. non-volitional weight loss, low body mass index (BMI), or reduced muscle mass) and an etiologic criterium (i.e. reduced food intake or assimilation, and disease burden or inflammation). Malnutrition was also determined using single parameters for impaired body composition, muscle strength or caloric intake (Table 1), and the combination of low BMI and unintentional weight loss as advised in current IBD guidelines. To screen for malnutrition, the Short Nutritional Assessment Questionnaire (SNAQ) and Malnutrition Universal Screening Tool (MUST) were completed. Independent risk factors (i.e. clinical and demographic factors) for malnutrition were analyzed by multivariable logistic regression. Of the 200 included patients (139 CD, 61 UC), 41 (20.5%) fulfilled the GLIM criteria, 95 (47.5%) had at least one parameter for malnutrition impaired (Figure 1). The fat free mass index was most often affected. When unintentional weight loss and/or low BMI was used as screening marker for nutritional status in line with current IBD guidelines, 29 (14.5%) patients would have been identified (Figure 2). Screening for malnutrition using the SNAQ and MUST detected 44 (22.0%) and 23 (12.9%) patients with a positive score. Only female sex was associated with malnutrition when at least one parameter was impaired (OR 2.47, 95% CI 1.35–4.51). Malnutrition prevalence among IBD outpatients according to the GLIM criteria was found to be 20.5%. Almost half of the IBD outpatients had malnutrition as defined by various single parameters and irrespective of disease characteristics. Screening instruments and/or markers according to current IBD guidelines, did not identify a substantial part of the patients. Therefore, screening for malnutrition is recommended for all IBD outpatients by multiple parameters, with special attention for assessing fat free mass and reduced intake.

A. Rezazadeh Ardabili, L. Janssen, M. Romberg-Camps, D. Keszthelyi, D. Jonkers, A. V. van Bodegraven, M. Pierik, Z. Mujagic

Chronic abdominal pain is highly prevalent in IBD patients in remission. The aetiology is incompletely understood, although persistent histologic inflammation, post-inflammatory visceral hypersensitivity, and altered gut-brain interaction are believed to contribute. Data on the characteristics of IBD patients suffering from chronic abdominal pain are sparse, yet essential for the identification of treatment targets. We investigated clinical, lifestyle and psychosocial factors associated with chronic abdominal pain in a real-world cohort of IBD patients in remission. A prospective multicentre study was performed enrolling consecutive IBD patients, between Jan 1, 2020 and Jul 1, 2021, using myIBDcoach, an established remote monitoring platform for IBD. Patient reported outcome measures on disease activity, lifestyle and psychosocial factors (i.e. depressive symptoms, anxiety, stress, and life events) were assessed in three-monthly intervals. Chronic abdominal pain in IBD in remission (IBDremissionPain+) was defined as an abdominal pain score ≥3 (1–10 numeric rating scale (NRS)) at ≥1/3 of all assessments combined with faecal calprotectin <150 μg/g in 90 days around periodic assessments. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for IBDremissionPain+ compared to patients in remission without chronic abdominal pain (IBDremissionPain-). In total, 559 patients were followed prospectively, of which 429 (76.7%) were in biochemical remission. Of these, 198 (46.2%) fulfilled the criteria for chronic abdominal pain. IBDremissionPain+ patients were characterized by female sex, higher BMI, and shorter disease duration compared to IBDremissionPain- (Table 1). IBDremissionPain+ patients reported significantly higher levels of stress, fatigue, depressive and anxiety symptoms, and occurrence of life events (Table 2). On multivariable logistic regression, female sex (aOR 2.58), shorter disease duration (<10years, aOR 2.31), higher BMI (aOR 1.06), higher levels of stress (aOR 1.19), fatigue (aOR 4.73), and life events (aOR 1.65) were all significantly associated with chronic abdominal pain (Table 3). The univariable association between pain and anxiety and depressive symptoms was modulated by stress in the multivariable analysis. In this real-world population of IBD patients in remission, 46.2% experience chronic abdominal pain, characterized by female sex, shorter disease duration, higher BMI, fatigue and psychosocial factors. The gut-brain interaction in this population is represented by higher levels of depressive and anxiety symptoms, but the relation to abdominal pain is potentially modulated through increased levels of perceived stress.

R. Loveikyte, M. Boer, C. N. van der Meulen, R. W. T. ter Steege, G. Tack, J. Kuyvenhoven, B. Jharap, M. K. Vu et al.

Iron deficiency (ID) and anaemia in Inflammatory Bowel Disease (IBD) are associated with reduced quality of life, worse disease outcomes, and an increase in healthcare costs. In the European guidelines, anaemia is listed as one of the treatment goals. The data on the prevalence of anaemia and ID are inconsistent. Therefore, we evaluated the prevalence of ID, anaemia, and potential risk factors in a large Dutch outpatient population. Between January and November 2021, consecutive adult outpatients with IBD, who did not have significant comorbidities associated with anaemia, were included in this study across 16 general, teaching, and academic hospitals within the Netherlands. Besides demographic and clinical data, relevant biochemical parameters such as haemoglobin (Hb), Mean Corpuscular Volume (MCV), iron indices, and inflammatory markers (e.g., C-reactive protein (CRP) and faecal calprotectin (FCP)) were extracted from medical records. Active IBD was defined by either CRP >5mg/L or FCP >150mg/g. ID was defined by ferritin <100µg/L in case of inflammation and <30µg/L in quiescent IBD, or transferrin saturation <20%. The Dutch national reference range was used to define anaemia: Hb <7.5mmol/L or <8.5mmol/L for females and males, respectively. The data were analysed by stratifying patients into Crohn’s Disease (CD) and Ulcerative Colitis (UC) groups, with the latter also including patients with IBD-unclassified (IBDU). In total, 2197 patients (1271 CD, 849 UC, and 77 IBDU) were included in the study. The overall prevalence of anaemia, iron-deficiency anaemia (IDA), and ID was: 18.0%, 12.2%, and 43.4%, respectively. The prevalence of all three conditions did not differ between the CD and UC groups (P>0.05). Severe anaemia (Hb<6.2 mmol/L) was observed only in 28 patients. ID was more frequently observed in biochemically active IBD compared with quiescent IBD (70.8% versus 23.9%; P<0.001). Female gender, younger age, low MCV, and a twofold increase in biochemical inflammation were associated with ID development in multivariable analysis: Log2FCP [OR 1.39; 95% CI: 1.29–1.50; P<0.001] and Log2platelets [OR 1.85; 95% CI: 1.16–2.95; P<0.01]. In multivariable analysis, low ferritin and MCV, inflammation, older age, and male gender were associated with a higher risk of anaemia; however, disease location or behaviour did not affect the risk of developing anaemia or ID. One in five ambulatory IBD patients presents with anaemia that is primarily caused by ID. Inflammation increases the risk of ID and anaemia regardless of IBD type or disease location. High ID prevalence suggests the need for screening and treatment optimisation.

S. Condés, M. del Río, D. Forrester, Admir Avdagić, K. Bielak, A. Bončina, M. Bošeľa, T. Hilmers et al.

This paper demonstrates the application of business intelligence in decision-making in digital advertising through a case study. Data used for analysis was collected during a test phase of an advertising platform. The study analyzes multiple types of traffic, related to countries, browsers, household incomes, and days of a week. Beside tabular reports, the paper presents how to visualize those results using Python libraries to make them more visually appealing. Furthermore, logistic regression was used to build models to detect relationships between the number of impressions and clicks. Finally, the authors propose multiple combinations of data that could be used to create different reports that lead to smarter decision-making and cost-effectiveness.

M. Santini, Sara Haberle, S. Židovec-Lepej, V. Savić, Marija Kusulja, N. Papić, K. Višković, Ivana Župetić et al.

West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.

Teodora Pejović, S. Kovačević, P. Brkić, J. Nešović-Ostojić

Tissue ischemia means insufficient blood flow to a certain area of the body. Interruption of the arterial blood supply leads to an imbalance between metabolic supply and demand and the development of tissue hypoxia. Tissue hypoxia induces metabolic changes that result in inflammation, increased production of reactive oxygen species, and cell death. If adequate blood flow is established in the ischemic tissue, there will be an increase in cellular damage, which is referred to as ischemic-reperfusion injury. Ischemia and ischemia-reperfusion injury are at the root of numerous diseases widely present in modern society, such as myocardial infarction, cerebral insult, acute kidney injury. For now, there is no way to directly affect cellular hypoxia, but the clinical treatment of hypoxic conditions is aimed at modulating global hypoxemia and increasing the amount of oxygen dissolved in the blood. Hyperbaric oxygenation (HBO) is a treatment during which the patient breathes 100% oxygen under a pressure of at least 1.4 atmospheres. Although the use of hyperbaric therapy was recorded as early as the 17th century, today this treatment is approved for a few indications.

Teodora Pejović, S. Kovačević, J. Nešović-Ostojić

Cadmium (Cd) is an extremely toxic metal that is widespread in nature. Due to its favorable properties, it was widely used in the industry for the production of alkaline batteries, accumulators, pigments, and colored alloys. However, it has been shown that exposure to low concentrations of cadmium leads to damage to many organs and organ systems, and the use of this metal in industry is reduced, and it is replaced by other, less harmful materials. Today, fossil fuel combustion and cigarette consumption are important sources of cadmium exposure. Numerous studies have examined the toxic effects of cadmium and they highlight the kidneys, liver, gonads as the organs that suffer the most damage. The kidneys, as the main place of cadmium storage in the body, are mostly exposed to its toxic effects. In the proximal tubular cells of the kidney, exposure to cadmium disrupts transport processes. Although ionized cadmium (Cd 2+) is thought to be largely responsible for the damage that occurs, the role of the cadmium and metallothionein complex (Cd-MT) cannot be ignored. Peritubular exposure to ionized cadmium indirectly leads to a decrease in the activity of the Na + /L-alanine cotransporter and a decrease in the rate of slow repolarization of the luminal membrane, while the Cd-MT complex leads to both direct and indirect inhibition of this transporter. Also, the Cd-MT complex inhibits Na + /Glucosa cotransporter activity. Exposure to cadmium also leads to a decrease in the endocytic uptake of low molecular weight proteins, which is accompanied by microalbuminuria.

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