Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease.

BACKGROUND: Population of patients with inflammatory bowel disease (IBD) is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia, and many others. AIM: To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases. An additional aim was to determine possible associations between GDF-15 and multiple clinical, anthropometric and laboratory parameters in patients with IBD. METHODS: This cross-sectional study included 90 adult patients diagnosed with IBD, encompassing both Crohn's disease (CD) and ulcerative colitis (UC), and 67 healthy age- and sex-matched controls. All patients underwent an extensive workup, including colonoscopy with subsequent histopathological analysis. Disease activity was assessed by two independent gastroenterology consultants specialized in IBD, employing well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined following an overnight fasting, using electrochemiluminescence immunoassay. RESULTS: In patients with IBD, serum GDF-15 concentrations were significantly higher in comparison to the healthy controls [800 (512-1154) pg/mL vs 412 (407-424) pg/mL, P < 0.001], whereas no difference in GDF-15 was found between patients with CD and UC [807 (554-1451) pg/mL vs 790 (509-956) pg/mL, P = 0.324]. Moreover, multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age, sex, and C-reactive protein levels (P = 0.016 and P = 0.049, respectively). Finally, an association between GDF-15 and indices of anemia was established. Specifically, negative correlations were found between GDF-15 and serum iron levels (r = -0.248, P = 0.021), as well as GDF-15 and hemoglobin (r = -0.351, P = 0.021). Accordingly, in comparison to IBD patients with normal hemoglobin levels, GDF-15 serum levels were higher in patients with anemia (1256 (502-2100) pg/mL vs 444 (412-795) pg/mL, P < 0.001). CONCLUSION: For the first time, we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls, and the results imply that GDF-15 might be involved in IBD pathophysiology. Yet, it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Role of B-Cell Activating Factor (BAFF) in Inflammatory Bowel Disease.

As early commencement of inflammatory bowel disease (IBD) treatment has been shown to substantially improve outcomes, it is of utmost importance to make a timely diagnosis of this disease. Despite undisputed sensitivity of fecal calprotectin, the most widely accepted IBD biomarker, in discriminating between irritable bowel syndrome (IBS) and IBD, as well as recognized role in monitoring disease activity and response to therapy, perhaps the biggest setback of calprotectin use in IBD is lack of specificity. Therefore, an additional biomarker in IBD is warranted. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, recently emerged as a viable candidate for this role. So far, overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus, where BAFF-inhibitor belimumab was approved for treatment. As BAFF levels were also shown to correlate with indices of IBD, in this review we aimed to summarize the current evidence with respect to the role of BAFF in diagnosis and assessing the activity of IBD, as well as putative therapeutic implications that may arise from exploring of this relation.

Nutritional Status and Indicators of 2-Year Mortality and Re-Hospitalizations: Experience from the Internal Clinic Departments in Tertiary Hospital in Croatia.

We aimed to provide insight into nutritional and clinical indicators of malnutrition risk and their influence on two-year mortality and re-hospitalization rate among patients hospitalized in internal clinic departments in the tertiary hospital in Croatia. Initially, data on 346 participants were obtained, while 218 of them where followed-up two years later. At baseline, the majority of participants were old and polymorbid (62.1% suffered from arterial hypertension, 29.5% from cancer, and 29.2% from diabetes). Even apparently presenting with satisfying anthropometric indices, 38.4% of them were at-risk for malnutrition when screened with the Nutritional Risk Screening-2002 (NRS-2002) questionnaire (NRS-2002 ≥ 3). More importantly, only 15.3% of all participants were prescribed an oral nutritional supplement during hospitalization. Those that were at-risk for malnutrition suffered significantly more often from cancer (54.9% vs. 20.6%; p < 0.001) and died more often in the follow-up period (42.7% vs. 23.5%; p < 0.003). Their anthropometric indices were generally normal and contradictory 46.3% were overweight and obese (body mass index (BMI) > 25 kg/m2). Only 36.6% of nutritionally endangered participants used an oral supplement in the follow-up period. NRS-2002 ≥ 3 correlated with anthropometric indices, glomerular filtration rate, age, and length of the initial hospital stay. Unlike other studies, NRS-2002 ≥ 3 was not an independent predictor of mortality and re-hospitalizations; other clinical, rather than nutritional parameters proved to be better predictors. Patients in our hospital are neither adequately nutritionally assessed nor managed. There is an urgent need to develop strategies to prevent, identify, and treat malnutrition in our hospital and post-discharge.

Mediterranean Diet Adherence and Dietary Attitudes in Patients with Inflammatory Bowel Disease.

A specific diet regimen is a promising way of managing inflammatory bowel disease (IBD), with the Mediterranean diet (MD) being a likely candidate due to its potential to modulate gut inflammation. Therefore, the aim of this study was to investigate nutritional habits and dietary attitudes of IBD patients, and to assess their adherence to the Mediterranean diet. The study enrolled 50 Crohn's disease and 44 ulcerative colitis patients, with clinical and laboratory parameters taken. Dietary attitudes were examined, and adherence to MD was assessed using the Mediterranean Diet Service Score (MDSS). Average MDSS score was 6.0 (5.0-7.0), while only nine participants fulfilled criteria for Mediterranean diet adherence. Moreover, all of them were men (p = 0.021). Low percentage of adherence to recommended guidelines was observed for eating olive oil (25.5%), fresh fruit (14.9%), and vegetables (10.6%). Significant positive correlation was observed between total MDSS points and high-density lipoprotein (HDL) cholesterol levels (p = 0.002). The majority of the patients (86.2%) considered that a more controlled diet could reduce their IBD symptoms, while 17% visited a nutritionist for diet advice. The majority of patients (84%) would visit educational programs regarding nutrition. In conclusion, adherence to MD was very low, while IBD patients were willing to extend their nutritional knowledge if proper educational programs were organized.

Serum adropin levels are reduced in patients with inflammatory bowel diseases.

Adropin is a novel peptide mostly associated with energy homeostasis and vascular protection. To our knowledge, there are no studies that investigated its relationship with inflammatory bowel diseases (IBD). The aim of this study was to compare serum adropin levels between 55 patients with IBD (30 Ulcerative colitis (UC) patients, 25 Crohn's disease (CD) patients) and 50 age/gender matched controls. Furthermore, we explored adropin correlations with IBD severity scores, hsCRP, fecal calprotectin, fasting glucose and insulin levels. Serum adropin levels were significantly lower in patients with IBD in comparison with the control group (2.89 ± 0.94 vs 3.37 ± 0.60 ng/mL, P = 0.002), while there was no significant difference in comparison of UC patients with CD patients (P = 0.585). Furthermore, there was a negative correlation between adropin and fecal calprotectin (r = -0.303, P = 0.025), whereas in the total study population, we found a significant negative correlation with fasting glucose levels (r = -0.222, P = 0.023). A multivariable logistic regression showed that serum adropin was a significant predictor of positive IBD status when enumerated along with baseline characteristics (OR 0.455, 95% CI 0.251-0.823, P = 0.009). Our findings imply that adropin could be involved in complex pathophysiology of IBD, but further larger scale studies are needed to address these findings.

Pathobiology of HER 2 positive small invasive (T1a,b) breast cancer: "A wolf in sheep's clothing".

Small invasive breast cancers (cancers with maximum diameter <1cm, T1a,b) become more prevalent form of breast cancer as a result of the introduction of breast cancer mammographic screening programs. Although associated with an excellent prognosis, T1a,b breast cancers are heterogeneous group of tumors with prognostically unfavorable subset of cases, primarily those with axillary lymph node metastases. To determine if the HER2 overexpression is associated with the prognostically unfavorable traditional clinicopathological features in this group of breast cancers, clinicopathological features (age, tumor size, histological type, histological grade, nodal status, hormone receptor status, proliferation index, lymphovascular invasion, ploidy) of 38 HER2 positive T1a,b cancers were compared with those of the control group consisting of 315 HER2 negative T1a,b cancers. The comparison of clinicopathological features was made using χ2 and t-test. HER2 positive T1a,b breast cancers were significantly associated with higher tumor grades (p<0.001), negative hormone receptors (p=0.008), presence of lymphovascular invasion (p=0.025), high proliferation index (p<0.001), and abnormal DNA content (p=0.04). We also noticed the higher frequency of lymph node positive cases in the HER2 positive group of cancers (p=0.05). There were no differences in age, tumor size and histological type between investigated groups. Our group of HER2 positive T1a,b breast cancers was associated with many unfavorable traditional prognostic factors, demonstrating that this subtype of early breast cancer has an aggressive biological phenotype which may have potential benefit from adjuvant chemo and immunotherapy.