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 overexpressed 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.

Inactive matrix Gla protein is elevated in patients with inflammatory bowel disease

BACKGROUND Matrix Gla protein(MGP)is a vitamin K dependent peptide which has an established role in suppression of vascular calcification.Recent studies have pointed to a possible link between immunomodulatory effect of MGP and inflammatory bowel disease(IBD).AIM To compare plasma levels of dephosphorylated and uncarboxylated MGP(dpucMGP)between IBD patients and controls.METHODS This cross-sectional study was conducted on 70 patients with IBD(30 patients with ulcerative colitis and 40 patients with Crohn’s disease)and 60 age and gender matching healthy controls.Plasma dp-ucMGP levels were analyzed from blood samples by CLIA method using IDS-iSYS InaKtif MGP(Immunodiagnostic Systems,Frankfurt,Germany)according to the manufacturer's instructions.fecal calprotectin(FC)levels were determined from stool samples by turbidimetric immunoassay method using Bühlmann fecal calprotectin turbo assay(Bühlmann Laboratories Aktiengesellschaft,Schonenbuch,Switzerland).Other parameters were analyzed according to the standard laboratory procedures.RESULTS Plasma levels of dp-ucMGP were significantly higher in patients with IBD compared to the healthy control group(629.83±124.20 pmol/mL vs 546.7±122.09 pmol/mL,P<0.001),and there was no significant difference between patients with Crohn’s disease and patients with ulcerative colitis(640.02±131.88 pmol/mL vs 616.23±113.92 pmol/mL,P=0.432).Furthermore,a significant positive correlation of plasma dp-ucMGP levels was found with both FC levels(r=0.396,P<0.001)and high sensitivity C-reactive protein(hsCRP)levels(r=0.477,P<0.001).Moreover,in the total study population a significant positive correlation was found between dp-ucMGP with age(r=0.210,P=0.016)and waist circumference(r=0.264,P=0.002).Multiple linear regression analysis showed that dp-ucMGP levels retained significant association with FC(β±SE,0.06±0.02,P=0.003).CONCLUSION Study results support experimental data of MGP immunomodulatory IBD effect and indicate potential involvement in the pathophysiology of the disease,and possibly extraintestinal manifestations.

Urotensin II levels in patients with inflammatory bowel disease

BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well.Furthermore,patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls.Since the features of IBD includes chronic inflammation and endothelial dysfunction as well,it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIM To determine serum UII levels in patients with IBD and to compare them to control subjects,as well as investigate possible associations with relevant clinical and biochemical parameters.METHODS This cross sectional study consecutively enrolled 50 adult IBD patients(26 with Crohn’s disease and 24 with ulcerative colitis)and 50 age and gender matched controls.Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines.Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation.Serum levels of UII were determined using the enzyme immunoassay kit for human UII,according to the manufacturer’s instructions.RESULTS IBD patients have significantly higher concentrations of UII when compared to control subjects(7.57±1.41 vs 1.98±0.69 ng/mL,P<0.001),while there were no significant differences between Crohn’s disease and ulcerative colitis patients(7.49±1.42 vs 7.65±1.41 ng/mL,P=0.689).There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels(r=0.491,P<0.001)and a significant negative correlation between serum UII levels and total proteins(r=-0.306,P=0.032).Additionally,there was a significant positive correlation between serum UII levels with both systolic(r=0.387,P=0.005)and diastolic(r=0.352,P=0.012)blood pressure.Moreover,serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity(r=0.425,P=0.048)and Simple Endoscopic Score for Crohn’s Disease(r=0.466,P=0.028)scores.Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide(β±standard error,0.262±0.076,P<0.001)and systolic blood pressure(0.040±0.017,P=0.030).CONCLUSION It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients,and its purpose should be investigated in further studies.

Impact of the COVID-19 pandemic on inflammatory bowel disease patients:A review of the current evidence

Since the initial coronavirus disease 2019(COVID-19)outbreak in China in December 2019,the infection has now become the biggest medical issue of modern medicine.Two major contributors that amplified the impact of the disease and subsequently increased the burden on health care systems were high mortality among patients with multiple co-morbidities and overcapacity of intensive care units.Within the gastroenterology-related community,particular concern was raised with respect to patients with inflammatory bowel disease(IBD),as those patients are prone to opportunistic infections mainly owing to their immunosuppressive-based therapies.Hence,we sought to summarize current knowledge regarding COVID-19 infection in patients with IBD.Overall,it seems that IBD is not a comorbidity that poses an increased risk for COVID-19 acquisition,except in patients treated with 5-aminosalicylates.Furthermore,outcomes of the infected patients are largely dependent on therapeutic modality by which they are treated,as some worsen the clinical course of COVID-19 infection,whereas others seem to dampen the detrimental effects of COVID-19.Finally,we discussed the present and the future impact of COVID-19 pandemic and concomitantly increased health care burden on IBD-management.