Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is ...considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 − 0.402 × age + 4.560 × 10−3 × age2 − 2.621 × 10−5 × age2 × MBP + 3.176 × 10−3 × age × MBP − 1.832 × 10−2 × MBP. MBP= (DBP) + 0.4(SBP − DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118–8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.
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.
Ulcerative colitis (UC) is a multifactorial disease of unknown precise etiology and immunopathogenesis. Peripheral blood granulocytes and monocytes/macrophages are the major sources of cytokines, ...which regulate inflammation. Leukocytapheresis (LCAP) is a method where blood is processed by apheresis system that removes lymphocytes and plasma before being returned to the body. We report the first case in Croatia where we used LCAP in the treatment of a patient with severe steroid-dependent UC. After 12 LCAP procedures, good clinical response was obtained and there were no significant adverse side effects noticed. The patient remained in clinical remission over two years in which he underwent regular follow ups at outpatient clinic. Over a 10-year follow-up period after LCAP, the patient had only occasional clinical symptoms of disease activity. The clinical course was complicated with the development of metastatic colorectal carcinoma, which points to the importance of regular disease monitoring rather than the increased risk of malignant disease after LCAP. Patients with UC are a demanding group of patients that warrant the search for novel treatment strategies other than conventional pharmacological therapies. Although LCAP is still not a common treatment modality in our daily practice, data from recent studies suggest it to be an effective and safe procedure in the management of active UC patients.
Abstract
Background and Aims
Endoscopy and the use of faecal calprotectin faecal CP are among the least-favoured methods for assessing disease activity by inflammatory bowel disease IBD patients; the ...handling/processing of faecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin enzyme-linked immunosorbent assay ELISA, CPa9-HNE, with the aim of quantifying neutrophil activity and neutrophil extracellular trap NET-osis and proposing a non-invasive method for monitoring disease activity in IBD patients.
Methods
In vitro cleavage was performed by mixing calprotectin S100A9/S100A8 with human neutrophil elastase HNE, and a novel HNE-derived calprotectin neo-epitope CPa9-HNE was identified by mass spectrometry for ELISA development. The CPa9-HNE ELISA was quantified in supernatants from ex vivo activated neutrophils and serum samples from patients with ulcerative colitis UC, n = 43, Crohn’s disease CD, n = 93, and healthy subjects HS, n = 23. For comparison, faecal CP and MRP8/14 biomarkers were also measured.
Results
CPa9-HNE was specific for activated neutrophils ex vivo. Serum CPa9-HNE levels were 4-fold higher in CD p <0.0001 and UC p <0.0001 patients than in HS. CPa9-HNE correlated well with the Simple Endoscopic Score SES-CD score r = 0.61, p <0.0001, MES r = 0.46, p = 0.0141, and the full Mayo score r = 0.52, p = 0.0013. CPa9-HNE was able to differentiate between CD and UC patients in endoscopic remission and moderate/severe disease activity (CD: area under the curve AUC = 0.82 p = 0.0003, UC: AUC = 0.87 p = 0.0004). The performance of CPa9-HNE was equipotent or slightly better than that of faecal CP.
Conclusions
Serum CPa9-HNE levels were highly associated with CD and UC patients. CPa9-HNE correlated with the SES-CD score and the full Mayo score, indicating a strong association with disease activity.
Introduction: The pandemic of obesity is strongly related to increase of chronic kidney disease (CKD) prevalence. The currently recommended CKD epidemiology collaboration (CKD EPI) equation has ...several serious limitations, particularly in obese subjects who have high body surface area (BSA). The aim of our study was to analyze differences in the prevalence of CKD between CKD EPI and de-indexed equations where individual BSA was used. Methods: In a total of 2,058 subjects (random sample from a general rural population, 29.65% obese), BSA was estimated using DuBois and DuBois and Moesteller equations and included into the de-indexed equations (CKD DBi, CKD Mi). CKD was classified according to the KDIGO guidelines, and glomerular hyperfiltration (GHF) was defined as 95th percentile, according to the gender and age decade. Results: In obese subjects, prevalence of CKD was significantly higher with CKD EPI than with CKD DBi and CKD Mi equations (9.5%, 6.1%, 5.3%, respectively; p < 0.001), while prevalence of GHF was significantly lower (3.8%, 12.3%, 12.8%, respectively; p < 0.001). Opposite results were observed in subjects with a body mass index <25 kg/m 2 for CKD (5%, 7.1%, 7.2%; p = 0.07) and GHF prevalence (6.1%, 1%, 0.6%; p < 0.001). Discussion/Conclusions: The prevalence of CKD is overestimated, and the prevalence of GHF is underestimated in obese subjects using the CKD EPI equation, i.e., the CKD EPI equation is unreliable in one-third of the population. De-indexed equations should be recommended instead of the CKD EPI equation in epidemiological studies until direct measurement of the glomerular filtration rate becomes more available.
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 <50 nmol/L and insuficiency as 50-75 nmol/L. Supplementation was defined as taking 800-2000 IU vitamin D daily. Untreated patients were defined as not taking supplementation and undertreated group as receiving supplementation but showing vitamin D deficiency or insuficiency despite treatment. Our study included 185 IBD patients, i.e. 126 (68.1%) with Crohn's disease (CD) and 59 (31.9%) with ulcerative colitis (UC). Overall, 108 (58.4%) patients had vitamin D deficiency and 60 (32.4%) patients vitamin D insuficiency. There were 16 (14.8%) and 11 (18.3%) treated patients in vitamin D deficiency and vitamin D insuficiency group, respectively. The rate of untreated patients was 81.7% (n=49) in vitamin D deficiency group and 85.2% (n=92) in vitamin D insuficiency group. Tumor necrosis factor alpha inhibitors were associated with higher serum vitamin D levels in CD and UC, and ileal involvement, ileal and ileocolonic resection with lower levels. In conclusion, not only is vitamin D deficiency common in IBD patients but the proportion of untreated and undertreated patients is considerably high. We suggest regular monitoring of vitamin D levels in IBD patients regardless of receiving vitamin D supplementation therapy. Key words: Inflammatory bowel diseases; Vitamin D deficiency; Crohn's disease; Colitis, ulcerative
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.
The aims of the study were to provide data on chronic kidney disease (CKD) prevalence in rural population and to analyze the association with cardiovascular risk factors and aging. A random sample of ...2193 farmers (1333 female (F) and 860 male (M), mean age 50.61±17.12) were enrolled. Questionnaire and clinical examination were conducted. Participants provided a spot urine and fasting blood sample. Estimated glomerular filtration rate (eGFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Subjects were classified according to the KDIGO guidelines. The overall prevalence of CKD (eGFR <60 mL/min/1.73 m
) was 8.83% (F
. M 9.9%
. 6.3%; p<0.001). Albuminuria (albumin-to-creatinine ratio >30 mg/g) was found in 8.45% (F
. M p>0.05). Sharp increase in CKD prevalence was found to begin after the sixth decade (29.44% in subjects older than 65 years; F
. M 30.9%
. 26.8%; p<0.01). The strongest predictor factors for CKD were age >65 years (OR 22.12), hypertension (OR 6.53), albuminuria (OR 5.71), fasting blood glucose >7 mmol/L (OR 5.49), diabetes (OR 3.07), abdominal obesity (OR 2.05) and non-smoking (OR 0.41). In multivariate analysis, age (OR 1.13), female gender (OR 0.60) and diabetes (OR 1.75) were the independent predictor factors for CKD. In conclusion, CKD prevalence is high in rural population, being higher in women than in men. In both genders, eGFR significantly decreased with aging. Aging is a significant independent predictor of CKD.
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.
The link between metabolic syndrome (MetS) and sarcopenia has not been extensively studied, but it is evident that they share several common features. Crucial mechanisms involved in ...sarcopenia-nonalcoholic fatty liver disease (NAFLD) interplay are based on effects of insulin resistance, chronic inflammation, oxidative stress, and crosstalk between organs by secretion of cytokines (hepatokines, adipokines, and myokines). Currently, published studies confirm the association of sarcopenia with the degree of NAFLD defined by liver histology. However, prospective studies that will give us information regarding the causal effect of NAFLD and sarcopenia are still needed. Furthermore, there is a need for a patient-friendly, noninvasive, low-cost method for detection of loss of skeletal muscle mass, strength, and physical performance in the context of NAFLD. Moreover, potential treatment strategies such as physical exercise and nutritional supplementation, that are usually a part of management of sarcopenia, should also be investigated in NAFLD patients, especially given the fact that for now, we do not have a good treatment option for NAFLD. Therefore, future investigations should combine studies on NAFLD and sarcopenia in terms of physical activity and nutritional interventions such as vitamin D supplementation. This review aims to report recent evidence concerning the links between sarcopenia and NAFLD and methods to assess sarcopenia.
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